48 results on '"Tamer Shoeib"'
Search Results
2. Unconventional Radical and Radical-Hole Site-Based Interactions in Halogen-Bearing Dimers and Trimers: A Comparative Study
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Mahmoud A. A. Ibrahim, Heba S. M. Abd Elhafez, Mohammed N. I. Shehata, Nayra A. M. Moussa, Shaban R. M. Sayed, Mahmoud E. S. Soliman, Muhammad Naeem Ahmed, Mohamed Khaled Abd El-Rahman, and Tamer Shoeib
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Chemistry ,QD1-999 - Published
- 2024
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3. Elucidating the potential of bimetallic mixed metal oxide (FeO/NiO) in fusion with pristine and N- and S-doped graphene oxide for biomedical applications
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Safeena Zafar, Bilal Ahmad Khan, Ikhtiar Ahmad, Muhammad Naeem Ahmed, Aroosa Zafar, Rasool Khan, Mohamed A. El-Tayeb, Ahmed M. Awad, Tamer Shoeib, and Mahmoud A.A. Ibrahim
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Graphene oxide ,Nanocomposites ,Bimetallic mixed metal oxide ,Antibacterial resistance ,XRD ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Antimicrobial resistance is attributed to acquiring new mechanisms by microbes to combat antimicrobial agents, highlighting the necessity to discover new antimicrobial agents to protect human health. Graphene and its derivatives have shown antimicrobial potential due to their physical and chemical distinctive features. Potent antibacterial properties were observed by decorating the surface of graphene and its derivatives with inorganic nanoparticles, such as metal and metal oxide. In an attempt to reliably overcome antimicrobial resistance, the multifunctional nanocomposites, including FeO/NiO, FeO/NiO/GO, FeO/NiO/N-GO, and FeO/NiO/S-GO, were synthesized using a wet chemical method. Accordingly, the structural analysis was performed using X-ray diffraction (XRD), infrared spectroscopy (IR), energy dispersive X-ray (EDX), ultraviolet-visible spectroscopy (UV–vis), and scanning electron microscopy (SEM). For antibacterial potential, the synthesized nanocomposites were tested against non-resistant and resistant strains of bacteria. Notably, moderate antibacterial potential was found for FeO/NiO/N-GO nanocomposite with a MIC value of 12.5 μg/mL, compared to the MIC of pure Ciprofloxacin, a positive control, with a value of 1.25 μg/mL. Toward antifungal potential, the synthesized nanocomposites were assessed against various spores of fungal strains. In this regard, the synthesized nanocomposites were demonstrated as potent antifungal agents. Among the synthesized nanocomposites, FeO/NiO and FeO/NiO/S-GO exhibited the highest ZOI against Aspergillus flavus. Additionally, the activity of these nanocomposites was evaluated by means of total reducing power (TRP), total antioxidant capacity (TAC), and free radical scavenging. Further, the antioxidant, brine shrimp lethality, and hemolytic potential of the synthesized nanocomposites were evaluated to compare their effectiveness. According to brine shrimp lethality, all synthesized nanocomposites were sufficiently active, with a calculated median lethal concentration (LC50) showing ≥ 50 % mortality. The obtained results provide a promising base for the incorporation of nanocomposites in pharmaceutical and biomedical products.
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- 2024
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4. A Comparative DFT Investigation of the Adsorption of Temozolomide Anticancer Drug over Beryllium Oxide and Boron Nitride Nanocarriers
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Mahmoud A. A. Ibrahim, Al-Shimaa S. M. Rady, Peter A. Sidhom, Shaban R. M. Sayed, Khalid Elfaki Ibrahim, Ahmed M. Awad, Tamer Shoeib, and Lamiaa A. Mohamed
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Chemistry ,QD1-999 - Published
- 2024
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5. Seasonal dynamics and ecological risks of organochlorine pesticides in Kafrelsheikh-Egypt: Implications for aquatic ecosystems and public health
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Samir Shamma, Mahmoud Dawood, Eslam M.A. El-Nahrery, Ahmed Shahat, Mayyada M.H. El-Sayed, Mohamed N. Hegazy, Hani N. Sewilam, Tamer Shoeib, and Anwar Abdelnaser
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Aquatic ecosystems ,Organochlorine pesticides ,Nile tilapia ,Ecological risk quotient ,Target hazard quotient ,Environmental sciences ,GE1-350 - Abstract
Kafrelsheikh, situated in the middle of the Nile Delta, significantly contributes to Egypt's aquaculture and agriculture sectors. However, the local use of organochlorine pesticides (OCPs) in agriculture is often a source of OCP residues in associated drainage waters, which may threaten aquatic ecosystems. These pesticides persist in local water bodies, jeopardizing aquatic ecosystems and potentially impacting human health. This comprehensive study assessed the seasonal variations of 17 OCPs in both water sources and Nile tilapia across eight fish farming locations in Kafrelsheikh. Using gas chromatography coupled with mass spectrometry (GC-MS), we detected OCP concentrations in water that varied seasonally where winter recorded the highest levels at 22.5 ng/mL and, summer showed the lowest levels at 6.2 ng/mL. Despite water samples occasionally showing risk quotients (RQs) greater than 1, indicating a potential threat to aquatic life, the OCP levels in Nile tilapia were sufficiently low, with target hazard quotients (THQ) below 1, suggesting no significant risk for human consumption. The research highlights a pressing need for regular environmental monitoring and stricter regulatory control over pesticide use to protect aquatic life and ensure the safety of aquaculture products. These findings provide a critical basis for policy-making, aimed at balancing agricultural productivity with environmental sustainability in regions heavily dependent on both.
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- 2024
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6. σ‑Hole Site-Based Interactions within Hypervalent Pnicogen, Halogen, and Aerogen-Bearing Molecules with Lewis Bases: A Comparative Study
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Mahmoud A.A. Ibrahim, Asmaa M.M. Mahmoud, Mohammed N.I. Shehata, Rehab R.A. Saeed, Nayra A.M. Moussa, Shaban R.M. Sayed, Mohamed Khaled Abd El-Rahman, and Tamer Shoeib
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Chemistry ,QD1-999 - Published
- 2024
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7. Sigma-Hole and Lone-Pair-Hole Site-Based Interactions of Seesaw Tetravalent Chalcogen-Bearing Molecules with Lewis Bases
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Mahmoud A. A. Ibrahim, Rehab R. A. Saeed, Mohammed N. I. Shehata, Nayra A. M. Moussa, Ahmed M. Tawfeek, Muhammad Naeem Ahmed, Mohamed K. Abd El-Rahman, and Tamer Shoeib
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Chemistry ,QD1-999 - Published
- 2023
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8. A green compliant hand-held selective electrode device for monitoring active pharmaceuticals and the kinetics of their degradation
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Norhan Badr ElDin, Eslam Dabbish, Esraa Fawaz, Mohamed K. Abd El-Rahman, and Tamer Shoeib
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Medicine ,Science - Abstract
Abstract An in-line smartphone connected to a screen-printed selective electrode hand-held device was used to determine the concentration of distigmine bromide (DB) in its pure and dosage forms as well as its degradation kinetics by continuously measuring the change in the produced emf over time. The main objective, supported by the data presented, is to produce a highly reliable smartphone integrated selective sensor as a portable analyzer with potential high cloud connectivity combining a wide linear dynamic range, the fastest response time with the lowest limits of detection and quantitation while best integrating green analytical chemistry principles. The choice of ionophore used in this approach was guided by computation and the data obtained was compared with traditional analytical techniques. DB, for which there are no previously reported stability-indicating methods and for which four novel such methods are proposed here, was selected as a model drug for this work. At-line UV-spectrophotometry DB assay was obtained by measuring the difference between the spectra of the degradation product and the same concentration of intact drug. The degradation kinetics were studied by this method through tracking the decrease of DB absorbance and/or the increase of a generated degradation product signal over time. Off-line separation based HPLC and TLC stability-indicating methods for DB were also presented. All methods employed in this work were validated for accuracy, precision, specificity, repeatability, linearity, range, detection and quantification limits according to the ICH guidelines and were applied to the analysis of laboratory prepared mixtures as well as commercial products. While all methods proposed were shown to be highly reliable, the smartphone integrated selective sensor is highlighted as a portable analyzer with potential high cloud connectivity and was shown to combine a wide linear dynamic range, the fastest response time with the lowest limits of detection and quantitation while best integrating green analytical chemistry principles.
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- 2023
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9. Benzothiazinone analogs as Anti-Mycobacterium tuberculosis DprE1 irreversible inhibitors: Covalent docking, validation, and molecular dynamics simulations.
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Mahmoud A A Ibrahim, Doaa G M Mahmoud, Alaa H M Abdelrahman, Khlood A A Abdeljawaad, Gamal A H Mekhemer, Tamer Shoeib, Mohamed A El-Tayeb, Peter A Sidhom, Paul W Paré, and Mohamed-Elamir F Hegazy
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Medicine ,Science - Abstract
Mycobacterium tuberculosis is a lethal human pathogen, with the key flavoenzyme for catalyzing bacterial cell-wall biosynthesis, decaprenylphosphoryl-D-ribose oxidase (DprE1), considered an Achilles heal for tuberculosis (TB) progression. Inhibition of DprE1 blocks cell wall biosynthesis and is a highly promising antitubercular target. Macozinone (PBTZ169, a benzothiazinone (BTZ) derivative) is an irreversible DprE1 inhibitor that has attracted considerable attention because it exhibits an additive activity when combined with other anti-TB drugs. Herein, 754 BTZ analogs were assembled in a virtual library and evaluated against the DprE1 target using a covalent docking approach. After validation of the employed covalent docking approach, BTZ analogs were screened. Analogs with a docking score less than -9.0 kcal/mol were advanced for molecular dynamics (MD) simulations, followed by binding energy evaluations utilizing the MM-GBSA approach. Three BTZ analogs-namely, PubChem-155-924-621, PubChem-127-032-794, and PubChem-155-923-972- exhibited higher binding affinities against DprE1 compared to PBTZ169 with ΔGbinding values of -77.2, -74.3, and -65.4 kcal/mol, versus -49.8 kcal/mol, respectively. Structural and energetical analyses were performed for the identified analogs against DprE1 throughout the 100 ns MD simulations, and the results demonstrated the great stability of the identified BTZ analogs. Physicochemical and ADMET characteristics indicated the oral bioavailability of the identified BTZ analogs. The obtained in-silico results provide promising anti-TB inhibitors that are worth being subjected to in-vitro and in-vivo investigations.
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- 2024
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10. A DFT investigation on the potential of beryllium oxide (Be12O12) as a nanocarrier for nucleobases.
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Mahmoud A A Ibrahim, Maggie N S Hanna, Al-Shimaa S M Rady, Peter A Sidhom, Shaban R M Sayed, Mohamed A El-Tayeb, Ahmed M Awad, Hatem Tallima, and Tamer Shoeib
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Medicine ,Science - Abstract
The study of the interactions between biomolecules and nanostructures is quite fascinating. Herein, the adsorption propensity of beryllium oxide (Be12O12) nanocarrier toward nucleobases (NBs) was investigated. In terms of DFT calculations, the adsorption tendency of Be12O12 toward NBs, including cytosine (NB-C), guanine (NB-G), adenine (NB-A), thymine (NB-T), and uracil (NB-U), was unveiled through various configurations. Geometrical, electronic, and energetic features for Be12O12, NBs, and their associated complexes were thoroughly evaluated at M06-2X/6-311+G** level of theory. The potent adsorption process within NBs∙∙∙Be12O12 complexes was noticed through favorable interaction (Eint) and adsorption (Eads) energies with values up to -53.04 and -38.30 kcal/mol, respectively. Generally, a significant adsorption process was observed for all studied complexes, and the favorability followed the order: NB-C∙∙∙ > NB-G∙∙∙ > NB-A∙∙∙ > NB-T∙∙∙ > NB-U∙∙∙Be12O12 complexes. Out of all studied complexes, the most potent adsorption was found for NB-C∙∙∙Be12O12 complex within configuration A (Eint = -53.04 kcal/mol). In terms of energy decomposition, SAPT analysis revealed electrostatic (Eelst) forces to be dominant within the studied adsorption process with values up to -99.88 kcal/mol. Analyzing QTAIM and NCI, attractive intermolecular interactions within the studied complexes were affirmed. From negative values of thermodynamic parameters, the nature of the considered adsorption process was revealed to be spontaneous and exothermic. Regarding density of state, IR, and Raman analyses, the occurrence of the adsorption process within NBs∙∙∙Be12O12 complexes was confirmed. Noticeable short recovery time values were observed for all studied complexes, confirming the occurrence of the desorption process. The findings provided fundamental insights into the potential application of Be12O12 nanocarrier in drug and gene delivery processes.
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- 2024
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11. Repurposing of drug candidates against Epstein-Barr virus: Virtual screening, docking computations, molecular dynamics, and quantum mechanical study.
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Mahmoud A A Ibrahim, Alaa M A Hassan, Eslam A R Mohamed, Gamal A H Mekhemer, Peter A Sidhom, Mohamed A El-Tayeb, Shahzeb Khan, Tamer Shoeib, Mahmoud E S Soliman, and Alaa H M Abdelrahman
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Medicine ,Science - Abstract
Epstein-Barr virus (EBV) was the first tumor virus identified in humans, and it is mostly linked to lymphomas and cancers of epithelial cells. Nevertheless, there is no FDA-licensed drug feasible for this ubiquitous EBV viral contagion. EBNA1 (Epstein-Barr nuclear antigen 1) plays several roles in the replication and transcriptional of latent gene expression of the EBV, making it an attractive druggable target for the treatment of EBV-related malignancies. The present study targets EBV viral reactivation and upkeep by inhibiting EBNA1 utilizing a drug-repurposing strategy. To hunt novel EBNA1 inhibitors, a SuperDRUG2 database (> 4,600 pharmaceutical ingredients) was virtually screened utilizing docking computations. In accordance with the estimated docking scores, the most promising drug candidates then underwent MDS (molecular dynamics simulations). Besides, the MM-GBSA approach was applied to estimate the binding affinities between the identified drug candidates and EBNA1. On the basis of MM-GBSA//200 ns MDS, bezitramide (SD000308), glyburide (SD001170), glisentide (SD001159), and glimepiride (SD001156) unveiled greater binding affinities towards EBNA1 compared to KWG, a reference inhibitor, with ΔGbinding values of -44.3, -44.0, -41.7, -40.2, and -32.4 kcal/mol, respectively. Per-residue decomposition analysis demonstrated that LYS477, ASN519, and LYS586 significantly interacted with the identified drug candidates within the EBNA1 binding pocket. Post-dynamic analyses also demonstrated high constancy of the identified drug candidates in complex with EBNA1 throughout 200 ns MDS. Ultimately, electrostatic potential and frontier molecular orbitals analyses were performed to estimate the chemical reactivity of the identified EBNA1 inhibitors. Considering the current outcomes, this study would be an adequate linchpin for forthcoming research associated with the inhibition of EBNA1; however, experimental assays are required to inspect the efficiency of these candidates.
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- 2024
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12. Hole interactions of aerogen oxides with Lewis bases: an insight into σ-hole and lone-pair-hole interactions
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Mahmoud A. A. Ibrahim, Mohammed N. I. Shehata, Hassan A. A. Abuelliel, Nayra A. M. Moussa, Shaban R. M. Sayed, Muhammad Naeem Ahmed, Mohamed K. Abd El-Rahman, Eslam Dabbish, and Tamer Shoeib
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σ-hole interactions ,lone-pair-hole interactions ,symmetry-adapted perturbation theory analysis ,point-of-charge analysis ,aerogen oxides ,Science - Abstract
σ-Hole and lone-pair (lp)-hole interactions of aerogen oxides with Lewis bases (LB) were comparatively inspected in terms of quantum mechanics calculations. The ZOn ⋯ LB complexes (where Z = Kr and Xe, n = 1, 2, 3 and 4, and LB = NH3 and NCH) showed favourable negative interaction energies. The complexation features were explained in light of σ-hole and lp-hole interactions within optimum distances lower than the sum of the respective van der Waals radii. The emerging findings outlined that σ-hole interaction energies generally enhanced according to the following order: KrO4 ⋯ < KrO⋯ < KrO3⋯ < KrO2⋯LB and XeO4⋯ < XeO⋯ < XeO2⋯ < XeO3⋯LB complexes with values ranging from –2.23 to –12.84 kcal mol−1. Lp-hole interactions with values up to –5.91 kcal mol−1 were shown. Symmetry-adapted perturbation theory findings revealed the significant contributions of electrostatic forces accounting for 50–65% of the total attractive forces within most of the ZOn⋯LB complexes. The obtained observations would be useful for the understanding of hole interactions, particularly for the aerogen oxides, with application in supramolecular chemistry and crystal engineering.
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- 2023
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13. Elucidating the adsorption of 2-Mercaptopyridine drug on the aluminum phosphide (Al12P12) nanocage: A DFT study
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Al-shimaa S.M. Rady, Nayra A.M. Moussa, Lamiaa A. Mohamed, Peter A. Sidhom, Shaban R.M. Sayed, Mohamed K. Abd El-Rahman, Eslam Dabbish, Tamer Shoeib, and Mahmoud A.A. Ibrahim
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Mercaptopyridine ,Aluminum phosphide nanocage ,DFT calculations ,SAPT ,Thermodynamic parameters ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Adsorption amplitude of the aluminum phosphide (Al12P12) nanocage toward the 2-Mercaptopyridine (MCP) drug was herein monitored based on density functional theory (DFT) calculations. The adsorption process through MCP⋅⋅⋅Al12P12 complex in various configurations was elucidated by means of adsorption (Eads) energies. According to the energetic affirmations, the Al12P12 nanocage demonstrated potential versatility toward adsorbing the MCP drug within the investigated configurations and exhibited significant negative adsorption energies up to −27.71 kcal/mol. Upon the results of SAPT analysis, the electrostatic forces showed the highest contributions to the overall adsorption process with energetic values up to −74.36 kcal/mol. Concurrently, variations of molecular orbitals distribution along with alterations in the energy gap (Egap) and Fermi level (EFL) of the studied nanocage were denoted after adsorbing the MCP drug. The favorable impact of water solvent within the MCP⋅⋅⋅Al12P12 complexes was unveiled and confirmed by negative solvation energy (ΔEsolv) values up to −17.75 kcal/mol. According to thermodynamic parameters, the spontaneous and exothermic natures of the considered adsorption process were proclaimed by negative values of ΔG and ΔH parameters. Significant changes in the IR and Raman peaks, along with the appearance of new peaks, were noticed, confirming the occurrence of the targeted adsorption process. Furthermore, the adsorption features of the MCP drug on the Al12N12 nanocage were elucidated and compared to the Al12P12 analog. The obtained results demonstrated the higher preferability of Al12P12 nanocage than the Al12N12 candidate towards adsorbing the MCP drug without structural distortion.
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- 2023
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14. Pyronaridine as a Bromodomain-Containing Protein 4-N-Terminal Bromodomain (BRD4-BD1) Inhibitor: In Silico Database Mining, Molecular Docking, and Molecular Dynamics Simulation
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Mahmoud A. A. Ibrahim, Mahmoud M. H. Abdelhamid, Khlood A. A. Abdeljawaad, Alaa H. M. Abdelrahman, Gamal A. H. Mekhemer, Peter A. Sidhom, Shaban R. M. Sayed, Paul W. Paré, Mohamed-Elamir F. Hegazy, and Tamer Shoeib
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cancer disease ,bromodomain-containing protein 4 ,SuperDRUG2 database ,molecular docking ,molecular dynamics simulations ,Organic chemistry ,QD241-441 - Abstract
BRD4 (bromodomain-containing protein 4) is an epigenetic reader that realizes histone proteins and promotes the transcription of genes linked to cancer progression and non-cancer diseases such as acute heart failure and severe inflammation. The highly conserved N-terminal bromodomain (BD1) recognizes acylated lysine residues to organize the expression of genes. As such, BD1 is essential for disrupting BRD4 interactions and is a promising target for cancer treatment. To identify new BD1 inhibitors, a SuperDRUG2 database that contains more than 4600 pharmaceutical compounds was screened using in silico techniques. The efficiency of the AutoDock Vina1.1.2 software to anticipate inhibitor-BRD4-BD1 binding poses was first evaluated based on the co-crystallized R6S ligand in complex with BRD4-BD1. From database screening, the most promising BRD4-BD1 inhibitors were subsequently submitted to molecular dynamics (MD) simulations integrated with an MM-GBSA approach. MM-GBSA computations indicated promising BD1 binding with a benzonaphthyridine derivative, pyronaridine (SD003509), with an energy prediction (ΔGbinding) of −42.7 kcal/mol in comparison with −41.5 kcal/mol for a positive control inhibitor (R6S). Pharmacokinetic properties predicted oral bioavailability for both ligands, while post-dynamic analyses of the BRD4-BD1 binding pocket demonstrated greater stability for pyronaridine. These results confirm that in silico studies can provide insight into novel protein–ligand regulators, specifically that pyronaridine is a potential cancer drug candidate.
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- 2023
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15. Adsorption Features of Tetrahalomethanes (CX4; X = F, Cl, and Br) on β12 Borophene and Pristine Graphene Nanosheets: A Comparative DFT Study
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Mahmoud A. A. Ibrahim, Amna H. M. Mahmoud, Nayra A. M. Moussa, Gamal A. H. Mekhemer, Shaban R. M. Sayed, Muhammad Naeem Ahmed, Mohamed K. Abd El-Rahman, Eslam Dabbish, and Tamer Shoeib
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tetrahalomethanes ,graphene nanosheet ,borophene nanosheet ,DFT ,Organic chemistry ,QD241-441 - Abstract
The potentiality of the β12 borophene (β12) and pristine graphene (GN) nanosheets to adsorb tetrahalomethanes (CX4; X = F, Cl, and Br) were investigated using density functional theory (DFT) methods. To provide a thorough understanding of the adsorption process, tetrel (XC-X3∙∙∙β12/GN)- and halogen (X3C-X∙∙∙β12/GN)-oriented configurations were characterized at various adsorption sites. According to the energetic manifestations, the adsorption process of the CX4∙∙∙β12/GN complexes within the tetrel-oriented configuration led to more desirable negative adsorption energy (Eads) values than that within the halogen-oriented analogs. Numerically, Eads values of the CBr4∙∙∙Br1@β12 and T@GN complexes within tetrel-/halogen-oriented configurations were −12.33/−8.91 and −10.03/−6.00 kcal/mol, respectively. Frontier molecular orbital (FMO) results exhibited changes in the EHOMO, ELUMO, and Egap values of the pure β12 and GN nanosheets following the adsorption of CX4 molecules. Bader charge transfer findings outlined the electron-donating property for the CX4 molecules after adsorbing on the β12 and GN nanosheets within the two modeled configurations, except the adsorbed CBr4 molecule on the GN sheet within the tetrel-oriented configuration. Following the adsorption process, new bands and peaks were observed in the band structure and density of state (DOS) plots, respectively, with a larger number in the case of the tetrel-oriented configuration than in the halogen-oriented one. According to the solvent effect affirmations, adsorption energies of the CX4∙∙∙β12/GN complexes increased in the presence of a water medium. The results of this study will serve as a focal point for experimentalists to better comprehend the adsorption behavior of β12 and GN nanosheets toward small toxic molecules.
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- 2023
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16. In-Silico Mining of the Toxins Database (T3DB) towards Hunting Prospective Candidates as ABCB1 Inhibitors: Integrated Molecular Docking and Lipid Bilayer-Enhanced Molecular Dynamics Study
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Mahmoud A. A. Ibrahim, Khlood A. A. Abdeljawaad, Alaa H. M. Abdelrahman, Peter A. Sidhom, Ahmed M. Tawfeek, Gamal A. H. Mekhemer, Mohamed K. Abd El-Rahman, Eslam Dabbish, and Tamer Shoeib
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MDR ,ABCB1 transporter ,Toxin and Toxin-Target Database (T3DB) ,docking computations ,MD simulations ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Multidrug resistance (MDR) is one of the most problematic issues in chemotherapeutic carcinoma therapy. The ABCB1 transporter, a drug efflux pump overexpressed in cancer cells, has been thoroughly investigated for its association with MDR. Thus, discovering ABCB1 inhibitors can reverse the MDR in cancer cells. In the current work, a molecular docking technique was utilized for hunting the most prospective ABCB1 inhibitors from the Toxin and Toxin-Target Database (T3DB). Based on the docking computations, the most promising T3DB compounds complexed with the ABCB1 transporter were subjected to molecular dynamics (MD) simulations over 100 ns. Utilizing the MM-GBSA approach, the corresponding binding affinities were computed. Compared to ZQU (calc. −49.8 kcal/mol), Emamectin B1a (T3D1043), Emamectin B1b (T3D1044), Vincristine (T3D4016), Vinblastine (T3D4017), and Vindesine (T3D2479) complexed with ABCB1 transporter demonstrated outstanding binding affinities with ΔGbinding values of −93.0, −92.6, −93.8, −92.2, and −90.8 kcal/mol, respectively. The structural and energetic investigations confirmed the constancy of the identified T3DB compounds complexed with the ABCB1 transporter during the 100 ns MD course. To mimic the physiological conditions, MD simulations were conducted for those identified inhibitors complexed with ABCB1 transporter in the presence of a POPC membrane. These findings revealed that Emamectin B1a, Emamectin B1b, Vincristine, Vinblastine, and Vindesine are promising ABCB1 inhibitors that can reverse the MDR. Therefore, subjecting those compounds to further in-vitro and in-vivo investigations is worthwhile.
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- 2023
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17. On the Use of Graphene Nanosheets for Drug Delivery: A Case Study of Cisplatin and Some of Its Analogs
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Mahmoud A. A. Ibrahim, Manar H. A. Hamad, Amna H. M. Mahmoud, Gamal A. H. Mekhemer, Shaban R. M. Sayed, Mohamed K. Abd El-Rahman, Peter A. Sidhom, Eslam Dabbish, and Tamer Shoeib
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graphene ,anti-cancer drug ,adsorption process ,DFT ,Pharmacy and materia medica ,RS1-441 - Abstract
Graphene (GN) nanosheets have been widely exploited in biomedical applications as potential nanocarriers for various drugs due to their distinct physical and chemical properties. In this regard, the adsorption behavior of cisplatin (cisPtCl2) and some of its analogs on a GN nanosheet was investigated in perpendicular and parallel configurations by using density functional theory (DFT). According to the findings, the most significant negative adsorption energies (Eads) within the cisPtX2⋯GN complexes (where X = Cl, Br, and I) were observed for the parallel configuration, with values up to –25.67 kcal/mol at the H@GN site. Within the perpendicular configuration of the cisPtX2⋯GN complexes, three orientations were investigated for the adsorption process, namely, X/X, X/NH3, and NH3/NH3. The negative Eads values of the cisPtX2⋯GN complexes increased with the increasing atomic weight of the halogen atom. The Br@GN site showed the largest negative Eads values for the cisPtX2⋯GN complexes in the perpendicular configuration. The Bader charge transfer outcomes highlighted the electron-accepting properties of cisPtI2 within the cisPtI2⋯GN complexes in both configurations. The electron-donating character of the GN nanosheet increased as the electronegativity of the halogen atom increased. The band structure and density of state plots revealed the occurrence of the physical adsorption of the cisPtX2 on the GN nanosheet, which was indicated by the appearance of new bands and peaks. Based on the solvent effect outlines, the negative Eads values generally decreased after the adsorption process in a water medium. The recovery time results were in line with the Eads findings, where the cisPtI2 in the parallel configuration took the longest time to be desorbed from the GN nanosheet with values of 61.6 × 108 ms at 298.15 K. The findings of this study provide better insights into the utilization of GN nanosheets in drug delivery applications.
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- 2023
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18. Anti-Cancer Peptides: Status and Future Prospects
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Gehane Ghaly, Hatem Tallima, Eslam Dabbish, Norhan Badr ElDin, Mohamed K. Abd El-Rahman, Mahmoud A. A. Ibrahim, and Tamer Shoeib
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anticancer peptides ,cancer therapy ,peptide conformation ,peptide mode of action ,cancer microenvironment ,Organic chemistry ,QD241-441 - Abstract
The dramatic rise in cancer incidence, alongside treatment deficiencies, has elevated cancer to the second-leading cause of death globally. The increasing morbidity and mortality of this disease can be traced back to a number of causes, including treatment-related side effects, drug resistance, inadequate curative treatment and tumor relapse. Recently, anti-cancer bioactive peptides (ACPs) have emerged as a potential therapeutic choice within the pharmaceutical arsenal due to their high penetration, specificity and fewer side effects. In this contribution, we present a general overview of the literature concerning the conformational structures, modes of action and membrane interaction mechanisms of ACPs, as well as provide recent examples of their successful employment as targeting ligands in cancer treatment. The use of ACPs as a diagnostic tool is summarized, and their advantages in these applications are highlighted. This review expounds on the main approaches for peptide synthesis along with their reconstruction and modification needed to enhance their therapeutic effect. Computational approaches that could predict therapeutic efficacy and suggest ACP candidates for experimental studies are discussed. Future research prospects in this rapidly expanding area are also offered.
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- 2023
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19. Enhanced Anticancer Activity of Nedaplatin Loaded onto Copper Nanoparticles Synthesized Using Red Algae
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Nada Mostafa Aboeita, Sherif Ashraf Fahmy, Mayyada M. H. El-Sayed, Hassan Mohamed El-Said Azzazy, and Tamer Shoeib
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nedaplatin ,CuO nanoparticles ,cancer cell lines ,green synthesis ,algal extract ,ultrasound-assisted extraction ,Pharmacy and materia medica ,RS1-441 - Abstract
Marine algae are a rich source of biologically active compounds that can be utilized in various food and pharmaceutical applications. In this study, ultrasound-assisted extraction (UAE) was optimized to maximize yield and total carbohydrate content extracted from the red algae, Pterocladia capillacea. The extract was shown to possess potent antioxidant activity of up to ~70%, and was successfully used as a reducing and capping agent in the green synthesis of copper nanoparticles, which were characterized by UV-spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Primarily, CuO nanoparticles with an average size of 62 nm were produced. FTIR spectra for the extract and algal-mediated CuO nanoparticles showed characteristic polysaccharide peaks. The synthesized CuO nanoparticles were subsequently loaded with nedaplatin where UV data suggested a complex formation. Nedaplatin release profiles showed a sustained release that reached a maximum at 120 h. The formulation was shown to have greater cytotoxicity relative to nedaplatin on hepatocellular carcinoma, breast cancer and ovarian cancer cell lines with IC50 values of 0.40 ± 0.08, 1.50 ± 0.12, and 0.70 ± 0.09 µg/mL, respectively. Loading nedaplatin onto CuO nanoparticles synthesized using red algae extract, greatly enhances its anticancer effect.
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- 2022
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20. Encapsulation of Nedaplatin in Novel PEGylated Liposomes Increases Its Cytotoxicity and Genotoxicity against A549 and U2OS Human Cancer Cells
- Author
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Salma El-Shafie, Sherif Ashraf Fahmy, Laila Ziko, Nada Elzahed, Tamer Shoeib, and Andreas Kakarougkas
- Subjects
chemotherapeutics ,liposomes ,platinum drugs ,nedaplatin ,DNA repair ,cancer treatment ,Pharmacy and materia medica ,RS1-441 - Abstract
Following the discovery of cisplatin over 50 years ago, platinum-based drugs have been a widely used and effective form of cancer therapy, primarily causing cell death by inducing DNA damage and triggering apoptosis. However, the dose-limiting toxicity of these drugs has led to the development of second and third generation platinum-based drugs that maintain the cytotoxicity of cisplatin but have a more acceptable side-effect profile. In addition to the creation of new analogs, tumor delivery systems such as liposome encapsulated platinum drugs have been developed and are currently in clinical trials. In this study, we have created the first PEGylated liposomal form of nedaplatin using thin film hydration. Nedaplatin, the main focus of this study, has been exclusively used in Japan for the treatment of non-small cell lung cancer, head and neck, esophageal, bladder, ovarian and cervical cancer. Here, we investigate the cytotoxic and genotoxic effects of free and liposomal nedaplatin on the human non-small cell lung cancer cell line A549 and human osteosarcoma cell line U2OS. We use a variety of assays including ICP MS and the highly sensitive histone H2AX assay to assess drug internalization and to quantify DNA damage induction. Strikingly, we show that by encapsulating nedaplatin in PEGylated liposomes, the platinum uptake cytotoxicity and genotoxicity of nedaplatin was significantly enhanced in both cancer cell lines. Moreover, the enhanced platinum uptake as well as the cytotoxic/antiproliferative effect of liposomal nedaplatin appears to be selective to cancer cells as it was not observed on two noncancer cell lines. This is the first study to develop PEGylated liposomal nedaplatin and to demonstrate the superior cell delivery potential of this product.
- Published
- 2020
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21. Chemotherapy Based on Supramolecular Chemistry: A Promising Strategy in Cancer Therapy
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Sherif Ashraf Fahmy, Jana Brüßler, Mohamad Alawak, Mayyada M. H. El-Sayed, Udo Bakowsky, and Tamer Shoeib
- Subjects
chemotherapy ,supermolecular ,anticancer drugs ,macrocycles ,Pharmacy and materia medica ,RS1-441 - Abstract
Chemotherapeutic agents are considered one of the strategies in treating cancer. However, their use is faced by many challenges, such as poor water solubility leading to poor bioavailability and non-selective targeting of cancerous cells leading to diminished therapeutic actions and systemic adverse effects. Many approaches were adopted to overcome these drawbacks and to achieve the targeted delivery of the chemotherapeutic agents to the cancerous cells while minimizing adverse effects. Recently, supramolecular systems such as macrocycles have gained attention in the field of cancer therapy for being able to encapsulate different anticancer drugs via either host-guest complexation or self-assembly leading to a myriad of advantages. This review highlights the most recent studies concerned with the design of such novel systems for cancer therapy.
- Published
- 2019
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22. Thermosensitive Liposomes Encapsulating Nedaplatin and Picoplatin Demonstrate Enhanced Cytotoxicity against Breast Cancer Cells
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Sherif Ashraf Fahmy, Eduard Preis, Alice Abu Dayyih, Mohamed Alawak, Hassan Mohamed El-Said Azzazy, Udo Bakowsky, and Tamer Shoeib
- Subjects
General Chemical Engineering ,General Chemistry - Abstract
Thermosensitive liposomes (TSL) have been used for localized temperature-responsive release of chemotherapeutics into solid cancers, with a minimum of one invention currently in clinical trials (phase III). In this study, TSL was designed using a lipid blend comprising 1,2-dipalmitoyl
- Published
- 2022
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23. Enhanced Anticancer Activity of Nedaplatin Loaded onto Copper Nanoparticles Synthesized Using Red Algae
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Nada Mostafa Aboeita, Sherif Ashraf Fahmy, Mayyada M. H. El-Sayed, Hassan Mohamed El-Said Azzazy, and Tamer Shoeib
- Subjects
nedaplatin ,CuO nanoparticles ,cancer cell lines ,green synthesis ,algal extract ,ultrasound-assisted extraction ,Pharmaceutical Science - Abstract
Marine algae are a rich source of biologically active compounds that can be utilized in various food and pharmaceutical applications. In this study, ultrasound-assisted extraction (UAE) was optimized to maximize yield and total carbohydrate content extracted from the red algae, Pterocladia capillacea. The extract was shown to possess potent antioxidant activity of up to ~70%, and was successfully used as a reducing and capping agent in the green synthesis of copper nanoparticles, which were characterized by UV-spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Primarily, CuO nanoparticles with an average size of 62 nm were produced. FTIR spectra for the extract and algal-mediated CuO nanoparticles showed characteristic polysaccharide peaks. The synthesized CuO nanoparticles were subsequently loaded with nedaplatin where UV data suggested a complex formation. Nedaplatin release profiles showed a sustained release that reached a maximum at 120 h. The formulation was shown to have greater cytotoxicity relative to nedaplatin on hepatocellular carcinoma, breast cancer and ovarian cancer cell lines with IC50 values of 0.40 ± 0.08, 1.50 ± 0.12, and 0.70 ± 0.09 µg/mL, respectively. Loading nedaplatin onto CuO nanoparticles synthesized using red algae extract, greatly enhances its anticancer effect.
- Published
- 2021
24. Fabrication of 3D lignosulfonate composited sponges impregnated by BiVO4/polyaniline/Ag ternary photocatalyst for synergistic adsorption-photodegradation of fluoroquinolones in water
- Author
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Boqiang Gao, Koukou Tao, Zhonghua Xi, Mayyada M.H. El-Sayed, Tamer Shoeib, and Hu Yang
- Subjects
General Chemical Engineering ,Environmental Chemistry ,General Chemistry ,Industrial and Manufacturing Engineering - Published
- 2022
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25. Evaluating the effects of the preoxidation of H2O2, NaClO, and KMnO4 and reflocculation on the dewaterability of sewage sludge
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Tamer Shoeib, Aimin Li, Yunong Tang, Hua Wei, and Hu Yang
- Subjects
Flocculation ,Environmental Engineering ,Health, Toxicology and Mutagenesis ,0208 environmental biotechnology ,Polyacrylamide ,Alkalinity ,02 engineering and technology ,010501 environmental sciences ,01 natural sciences ,law.invention ,chemistry.chemical_compound ,Extracellular polymeric substance ,law ,Environmental Chemistry ,Filtration ,0105 earth and related environmental sciences ,Public Health, Environmental and Occupational Health ,General Medicine ,General Chemistry ,Pulp and paper industry ,Pollution ,Dewatering ,020801 environmental engineering ,Filter cake ,chemistry ,Sludge - Abstract
The preoxidation effects of H2O2, NaClO, and KMnO4 on the dewaterability of sewage sludge were compared by analyzing the changes in specific resistance to filtration (SRF), filter cake moisture content (FCMC), extracellular polymeric substance (EPS) fractions and components, and floc properties. The three oxidants varied in oxidation efficiency and exhibited distinctive mechanisms. NaClO not only destroyed sludge flocs and EPSs but also effectively caused cell lysis, resulting in release of a considerable amount of organic matters and subsequently significant deterioration of dewatering performance. The oxidation of H2O2 and KMnO4 was relatively mild and occurred mainly on the outer layers of the sludge flocs and cell-bound EPSs. By contrast, the SRF and FCMC of the sludge conditioned with a low dose of KMnO4 were slightly improved, and a fraction of soluble EPS was compressed because of the coagulation effect of the oxidation product MnO2. The pH of the sludge conditioned with H2O2 and KMnO4 showed no considerable change. Meanwhile, NaClO evidently increased the alkalinity of the sludge because of the hydrolysis effect. After the pH of the NaClO-treated sludge was readjusted to 7.0, the partial protonation efficiency slightly alleviated the deterioration of sludge dewatering performance. The preoxidized sludge was then subjected to reflocculation treatment using FeCl3, polyacrylamide, and a cationic starch-based flocculant, respectively. The combined treatment of preoxidation and reflocculation showed a high dewatering efficiency owing to their synergistic effect.
- Published
- 2019
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26. Novel approach for effective removal of methylene blue dye from water using fava bean peel waste
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Tamer Shoeib, Omar S. Bayomie, Mayyada M. H. El-Sayed, Noha Youssef, Hu Yang, and Haitham Kandeel
- Subjects
Sonication ,lcsh:Medicine ,02 engineering and technology ,010501 environmental sciences ,complex mixtures ,01 natural sciences ,Article ,chemistry.chemical_compound ,symbols.namesake ,Adsorption ,lcsh:Science ,0105 earth and related environmental sciences ,Multidisciplinary ,Aqueous solution ,lcsh:R ,Biosorption ,Langmuir adsorption model ,Sorption ,021001 nanoscience & nanotechnology ,Environmental sciences ,Chemistry ,chemistry ,Wastewater ,symbols ,lcsh:Q ,0210 nano-technology ,Methylene blue ,Nuclear chemistry - Abstract
Fava bean peels, Vicia faba (FBP) are investigated as biosorbents for the removal of Methylene Blue (MB) dye from aqueous solutions through a novel and efficient sorption process utilizing ultrasonic-assisted (US) shaking. Ultrasonication remarkably enhanced sorption rate relative to conventional (CV) shaking, while maintaining the same sorption capacity. Ultrasonic sorption rate amounted to four times higher than its conventional counterpart at 3.6 mg/L initial dye concentration, 5 g/L adsorbent dose, and pH 5.8. Under the same adsorbent dose and pH conditions, percent removal ranged between 70–80% at the low dye concentration range (3.6–25 mg/L) and reached about 90% at 50 mg/L of the initial dye concentration. According to the Langmuir model, maximum sorption capacity was estimated to be 140 mg/g. A multiple linear regression statistical model revealed that adsorption was significantly affected by initial concentration, adsorbent dose and time. FBP could be successfully utilized as a low-cost biosorbent for the removal of MB from wastewater via US biosorption as an alternative to CV sorption. US biosorption yields the same sorption capacities as CV biosorption, but with significant reduction in operational times.
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- 2020
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27. Liposoame characterization protocol v1
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Sherif Ahmed Fahmy and Tamer Shoeib
- Abstract
l
- Published
- 2019
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28. Evaluating the effects of the preoxidation of H
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Hua, Wei, Yunong, Tang, Tamer, Shoeib, Aimin, Li, and Hu, Yang
- Subjects
Sewage ,Extracellular Polymeric Substance Matrix ,Cations ,Acrylic Resins ,Flocculation ,Water ,Hydrogen Peroxide ,Oxidation-Reduction ,Waste Disposal, Fluid ,Filtration - Abstract
The preoxidation effects of H
- Published
- 2019
29. Organophosphate esters in house dust: A comparative study between Canada, Turkey and Egypt
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Melis Yalçın, Yasmeen Hassan, Cafer Turgut, Sedef Tepe, Perihan Binnur Kurt-Karakus, Glenys M. Webster, Liisa M. Jantunen, and Tamer Shoeib
- Subjects
Environmental Engineering ,010504 meteorology & atmospheric sciences ,Turkey ,010501 environmental sciences ,01 natural sciences ,Toxicology ,chemistry.chemical_compound ,Frequency detection ,Environmental Chemistry ,Humans ,Waste Management and Disposal ,0105 earth and related environmental sciences ,Flame Retardants ,British Columbia ,Organophosphate ,Dust ,Esters ,Environmental Exposure ,Pollution ,Organophosphates ,chemistry ,13. Climate action ,Air Pollution, Indoor ,Housing ,Environmental science ,Egypt ,Environmental Monitoring - Abstract
Organophosphate esters (OPEs) are commonly used as flame retardants (FRs) and plasticizers. The usage of OPEs has increased recently due to the ban of several brominated flame retardants, but information on levels in the environment, including the indoor environment is still limited. We investigated the occurrence and distribution of 12 OPEs in urban house dust from Vancouver, Canada; Istanbul, Turkey; and Cairo, Egypt. The medianSOPE concentration was 41.4 mu g/g in the Vancouver samples while median levels in Istanbul and Cairo were significantly lower. The median composition profiles of OPEs in Vancouver and Cairo were dominated by tris (2-butoxyethyl) phosphate (TBOEP), accounting for 56 and 92% of total OPEs respectively while it showed a detection frequency of only 14% in Istanbul. Tris (2-chloropropyl) phosphate (TCPP) was the most abundant chlorinated OPE representing 20 and 36% of the total OPEs in Vancouver and Istanbul respectively, but was below the detection limit in the Cairo dust samples. Consistent with other studies, SOPE concentrations were similar to 1 to 2 orders of magnitude higher than PBDEs and currently used flame retardants in the same dust samples. The mean estimated daily intakes (EDI) of SOPE from dust were 115, 38 and 9 ng/kg/bw/day in Vancouver, Cairo and Istanbul respectively for toddlers where adults were similar to 10 times lower. The total toddler OPE intake ranged from 115 to 2900, 38 to 845 and from9 to 240 ng/kg bw/day across the three cities. TBOEP had the largest contribution to the EDI in both toddler and adults, where toddler TBOEP exposures via dust represented 4% to 80%, 2% to 44% and 0.1% to 6% of the Reference Doses (RfD) in the mean and high intake scenarios for toddlers in Vancouver, Cairo and Istanbul respectively. Crown Copyright (C) 2018 Published by Elsevier B.V. All rights reserved.
- Published
- 2018
30. Aroma-loaded microcapsules with antibacterial activity for eco-friendly textile application: synthesis, characterization, release, and green grafting
- Author
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M.F. Barreiro, Isabel Fernandes, Alírio E. Rodrigues, Tamer Shoeib, and Asma Sharkawy
- Subjects
food.ingredient ,Limonen ,General Chemical Engineering ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Vanilin ,Industrial and Manufacturing Engineering ,Chitosan ,chemistry.chemical_compound ,food ,Tannic acid ,Organic chemistry ,Microencapsulation ,Aroma ,Limonene ,Coacervate ,Chitosan/gum arabic ,biology ,Vanillin ,Textiles ,General Chemistry ,021001 nanoscience & nanotechnology ,biology.organism_classification ,0104 chemical sciences ,chemistry ,Polyglycerol polyricinoleate ,Gum arabic ,Antimicrobial ,0210 nano-technology ,Nuclear chemistry - Abstract
Fragrant and antimicrobial properties were conferred to cotton fabrics following microencapsulation using green materials. Limonene and vanillin microcapsules were produced by complex coacervation using chitosan/gum Arabic as shell materials and tannic acid as hardening agent. The effect of two emulsifiers; Span 85 and polyglycerol polyricinoleate (PGPR), on the encapsulation efficiency (EE%), microcapsule’s size and morphology, and cumulative release profiles was studied. The mean diameter of the produced microcapsules ranged between 10.4 and 39.0 μm, whereas EE% was found to be between 90.4% and 100%. The use of Span 85 resulted in mononuclear morphology while PGPR gave rise to polynuclear structures, regardless of the core material (vanillin or limonene). The obtained microcapsules demonstrated a sustained release pattern; namely the total cumulative release of the active agents after 7 days at 37 ± 1 °C was 75%, 52% and 19.4% for the polynuclear limonene microcapsules, the mononuclear limonene microcapsules and the polynuclear vanillin microcapsules, respectively. Grafting of the produced microcapsules onto cotton fabrics through na esterification reaction using citric acid as a nontoxic cross-linker followed by thermofixation and curing, was confirmed by SEM and FTIR spectroscopy. Standard antibacterial assays conducted on both microcapsules alone and impregnated onto the fabrics indicated a sustained antibacterial activity. info:eu-repo/semantics/publishedVersion
- Published
- 2017
31. A study on the physicochemical properties and cytotoxic activity of p-sulfocalix[4]arene-nedaplatin complex
- Author
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Jana Brüßler, Nino Russo, Emilia Sicilia, Fortuna Ponte, Mohamed K. Abd El-Rahman, Udo Bakowsky, Sherif Ashraf Fahmy, and Tamer Shoeib
- Subjects
History ,chemistry.chemical_compound ,Chemistry ,Cytotoxic T cell ,Nedaplatin ,Pharmacology ,Computer Science Applications ,Education - Abstract
Macromolecules including macrocyclic species have been reported to have the potential to encapsulate biologically active compounds such as drugs through host-guest complexation to increase their solubility, stability and bioavailability. Here we investigate the complexation between nedaplatin, a second generation antineoplastic drug, and p-4-sulfocalix[4]arene, a macromolecule possessing a bipolar amphiphilic structure with good biocompatibility and relatively low haemolytic toxicity for potential use as a drug delivery system. Data from 1H NMR, UV-Vis spectroscopy, Job’s plot analysis, HPLC, DSC and DFT calculations are detailed and suggest the formation of a 1:1 complex. The stability constant of the complex was experimentally estimated to be 3.6 × 104 M−1 and 2.1 × 104 M−1 which correspond to values of −6.2 and −5.9 kcal mol−1, respectively for the free energy of complexation while the interaction free energy is calculated to be −4.9 kcal mol−1. The formed species is shown to be stabilised in solution through hydrogen bonding between the host and the guest. The complex displayed enhanced antitumor activity against MDA-MB-231 cells compared to nedaplatin which may allow for its application in cancer therapy.
- Published
- 2019
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32. An ICP-MS, ESI-MS and molecular modelling investigation of homogeneous gallium affinity tagging (HMAT) of phosphopeptides
- Author
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Eslam M. Moustafa, Claire L. Camp, Barry L. Sharp, Helen J. Reid, and Tamer Shoeib
- Subjects
Chromatography ,Protein mass spectrometry ,Chemistry ,Electrospray ionization ,Selected reaction monitoring ,Analytical chemistry ,Condensed Matter Physics ,Top-down proteomics ,Tandem mass spectrometry ,Mass spectrometry ,Sample preparation in mass spectrometry ,Physical and Theoretical Chemistry ,Instrumentation ,Inductively coupled plasma mass spectrometry ,Spectroscopy - Abstract
Protein phosphorylation and de-phosphorylation, provide one of the most common signalling pathways within cells, being involved in regulating cellular processes, mediating enzyme inhibition, protein–protein recognition and protein degradation. Compared with normal proteomics, phosphoproteomics poses some additional challenges requiring more initial separation and additional sensitivity to detect and quantify potentially ultra-low abundance species. In this work, the selective detection of phosphopeptides is described based on the incorporation of a metal tag, gallium–N,N-biscarboxymethyl lysine (Ga-LysNTA), in solution before separation and detection by liquid chromatography coupled to inductively coupled plasma mass spectrometry (LC–ICP-MS). Experimental and theoretical characterisation of the resulting Ga–phosphopeptide complex is presented based on linear ion trap electrospray ionisation mass spectrometry (ESI-MS), Fourier transform mass spectrometry (FT-MS) and molecular modelling data. Linear ion trap electrospray ionisation mass spectrometry (ESI-MS) was employed to study the interaction of the gallium tag with platelet derived growth factor beta receptor (s-PDGF), a small phosphopeptide. In addition high resolution Fourier transform mass spectrometry (FT-MS) was used for accurate mass determination and multistage tandem mass spectrometry of the gallium–s-PDGF complex identified the fragmentation pathway. Finally, molecular modelling was used to investigate the energetically favoured structures of both the Ga-LysNTA material and the s-PDGF–Ga-LysNTA complex.
- Published
- 2013
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33. Determination of Pt–DNA adducts and the sub-cellular distribution of Pt in human cancer cell lines and the leukocytes of cancer patients, following mono- or combination treatments, by inductively-coupled plasma mass spectrometry
- Author
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Aref Zayed, Anne L. Thomas, Joanna P. Wood, George D. D. Jones, Sarah Taylor, Helen J. Reid, Tamer Shoeib, and Barry L. Sharp
- Subjects
Cisplatin ,A549 cell ,Chromatography ,Chemistry ,Cell ,Condensed Matter Physics ,Oxaliplatin ,Cytosol ,Folinic acid ,medicine.anatomical_structure ,FOLFOX ,In vivo ,medicine ,Physical and Theoretical Chemistry ,Instrumentation ,Spectroscopy ,medicine.drug - Abstract
This paper describes methodologies, based on sector field inductively-coupled plasma mass spectrometry (SF-ICP-MS), and their application in the holistic study of the fate of Pt in human cell populations following treatment with cis- or oxaliplatin and combination treatments. Pt–DNA adduct formation data at several time points has been determined in the leukocytes from patients undergoing Pt-based chemotherapy demonstrating significant inter-patient variability and excellent reproducibility of the assay. The sensitivity of the technique enabled quantitation of as little as 0.2 Pt adducts per 10 6 nucleotides using 10 μg of patient DNA. Further, the first ever reported in vivo sub-cellular Pt fractionation data on a patient sample is presented indicating the feasibility of applying the methods presented here in a clinical environment. For in vitro studies, three cell models were used: A549 human lung adenocarcinoma epithelial cells were exposed to 50 μM cisplatin for 1 h; HCA7 human colorectal cancer cells were treated with either FOLFOX (200 μM 5-fluorouracil, 200 μM folinic acid and 50 μM oxaliplatin) or 50 μM oxaliplatin; and HT29 human colorectal cancer cells were treated with 50 μM oxaliplatin in combination with 20 μM methaneseleninic acid, CH 3 SeO 2 H (MSA). The cells were harvested and either the DNA extracted and/or a commercially available kit used to fractionate the treated cells into four sub-cellular compartments. Each of the sub-cellular fractions and extracted DNA were digested separately, evaporated to dryness and reconstituted in 2% nitric acid for analysis by SF-ICP-MS. The sub-cellular Pt distribution for cisplatin treated A549 cells was shown to be as follows: ∼70% localized in the cytosol, ∼17% in the membrane and membrane localized fraction, ∼9% in the nuclear fraction and ∼4% in the cytoskeletal fraction. Both FOLFOX and oxaliplatin treated HCA7 cells showed comparable sub-cellular Pt distributions, and Pt–DNA adduct formation was similar for the oxaliplatin and FOLFOX treatments with adduct yields of 5.6 and 5.5 adducts per 10 6 nucleotides respectively. It was found that the combination of oxaliplatin with 20 μM MSA did not change the distribution of Pt or significantly alter its accumulation in the cytosol of the HT29 cells. Mass balance experiments showed a >99% recovery of the total Pt in the sub-cellular fractions. These experiments are the first to provide such a detailed quantitation of Pt-drug partitioning and they show that the Pt broadly follows the total protein content of the individual compartments with the majority being scavenged in the cytosol compartment.
- Published
- 2011
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34. Poly- and perfluoroalkyl substances (PFASs) in indoor dust and food packaging materials in Egypt: Trends in developed and developing countries
- Author
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Tamer Shoeib, Cassandra Rauert, Tom Harner, and Yasmeen Hassan
- Subjects
Environmental Engineering ,010504 meteorology & atmospheric sciences ,Health, Toxicology and Mutagenesis ,Developing country ,010501 environmental sciences ,01 natural sciences ,Air pollutants ,Limit of Detection ,Environmental monitoring ,Environmental Chemistry ,Humans ,Developing Countries ,0105 earth and related environmental sciences ,Detection limit ,Air Pollutants ,Fluorocarbons ,Developed Countries ,Public Health, Environmental and Occupational Health ,Food Packaging ,Dust ,General Medicine ,General Chemistry ,Pollution ,Food packaging ,Human exposure ,Environmental chemistry ,Environmental science ,Egypt ,Environmental Monitoring - Abstract
PFASs concentrations in dust samples collected from three microenvironments in Cairo ranged from 1.3 to 69 ng g(-1) with FTOHs being dominant. The 8:2 FTOH was detected in all samples. Among the FOSAs and FOSEs the MeFOSE was dominant while among ionic PFASs, PFOS and PFOA were most prominent. The concentrations of PFASs were among the lowest worldwide. Correlations between worldwide concentrations of PFOS + PFOA and country development indexes highlight higher usage and human exposure in more developed countries. Food packaging was analyzed for PFSAs, PFCAs and PAPs. The 6:2 and 8:2 monoPAPs were found to be above the MDL in 18% of the samples. PFOA was detected in 79% of the samples with median concentration of 2.40 ng g(-1). PFOS was detected in 58% of the samples with median concentration of 0.29 ng g(-1) while PFHxS and PFDS were below detection limit. Different human exposure scenarios were estimated.
- Published
- 2015
35. The fragmentation of protonated tyrosine and iodotyrosines: The effect of substituents on the losses of NH3 and of H2O and CO
- Author
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Alan C. Hopkinson, Junfang Zhao, Tamer Shoeib, and K. W. Michael Siu
- Subjects
Chemistry ,Ketene ,Protonation ,Condensed Matter Physics ,Tandem mass spectrometry ,Transition state ,Dissociation (chemistry) ,chemistry.chemical_compound ,Crystallography ,Hammett equation ,Fragmentation (mass spectrometry) ,Computational chemistry ,Density functional theory ,Physical and Theoretical Chemistry ,Instrumentation ,Spectroscopy - Abstract
The gas-phase dissociation chemistries of protonated 3-iodo- l -tyrosine, 3,5-diiodo- l -tyrosine and 3,3′,5,5′-tetraiodo-thyronine (thyroxine) have been examined using a combination of tandem mass spectrometry and density functional theory (DFT) calculations. It was found that, at low collision energy, all protonated tyrosines exhibit common fragmentation pathways, including the competitive eliminations of NH3 and the concomitant loss of H2O and CO, but there are significant differences in relative abundances, depending on the combined electron-donating abilities of the substituents in the phenyl ring. The ions initially formed by loss of NH3 are phenonium ions, but subsequent fragmentation is most easily understood in terms of the isomeric benzyl cation structures. These [M + H − NH3]+ ions fragment at relatively low collision energies, mainly by loss of ketene; by contrast, the [M + H − H2O − CO]+ ions are more stable towards dissociation. At higher collision energies, losses of one, two and even three iodine atoms were observed. DFT calculations (at the B3LYP/DZVP level of theory) were performed on protonated 3-iodotyrosine to compare the reaction profiles for the fragmentation mechanisms. The iodo-substituent in the 3-position is weakly electron-withdrawing and this results in a barrier (27.5 kcal/mol at 0 K) that is slightly higher than that for protonated tyrosine (26.8 kcal/mol). The phenoxy group PhO– is a weaker electron-donor than HO– and protonated 3,5-diiodo-4-phenoxytyrosine has an even higher barrier (31.1 kcal/mol) to NH3 loss than protonated 3,5-diiodotyrosine (28.8 kcal/mol). Linear free energy plots for Δ H 0 ° ‡ and Δ G 298 ° ‡ against σ+ for the four protonated tyrosine derivatives show good correlations. More importantly, as the products of the dissociation are higher in energy than the transition states to their formation, the plots of Δ H 0 ° and Δ G 298 ° for the overall reaction for NH3 loss also correlate very well with σ+ (correlation coefficients of 0.99 and 0.98, respectively). The positive slopes of these Hammett plots show that the barriers to the loss of NH3 by the neighboring-group mechanism are increased by the presence of electron-withdrawing groups in the phenyl rings.
- Published
- 2006
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36. Investigations of the gas-phase reactivity of Cu+ and Ag+ glycine complexes towards CO, D2O and NH3
- Author
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K. W. Michael Siu, Tamer Shoeib, Diethard K. Bohme, Alan C. Hopkinson, and Doina Caraiman
- Subjects
Metal ions in aqueous solution ,Inorganic chemistry ,Condensed Matter Physics ,Dissociation (chemistry) ,Adduct ,Reaction rate ,Metal ,chemistry.chemical_compound ,chemistry ,visual_art ,Reagent ,visual_art.visual_art_medium ,Density functional theory ,Physical and Theoretical Chemistry ,Instrumentation ,Spectroscopy ,Carbon monoxide - Abstract
The room-temperature reactivities of complexes of Cu + and Ag + with glycine have been investigated using an inductively coupled plasma-selected ion flow tube (ICP-SIFT)/multicollision-induced dissociation (CID) tandem mass spectrometer. These complexes were produced in a flow tube, collisionally thermalized and then allowed to react with CO, D 2 O or NH 3 . The measured reactivities of the CuGly + and AgGly + complexes have been compared with those of the bare metal cations towards the same neutral reagents. All observed reactions resulted in adduct formation, with helium buffer gas presumably acting as a stabilizing agent. Reaction rate enhancements of up to three orders of magnitude and lower extents of ligation were the main characteristics of the reactions initiated by the metal cation–glycine adducts as compared with those initiated by the bare metal cations. The kinetic information combined with equilibrium analyses and CID results suggest that, irrespective of the reagent, ligation to CuGly + is stronger than to AgGly + and, in both instances, ligation of carbon monoxide and water has comparable strengths, while much stronger coordination is achieved with ammonia. The structures of the complexes have been investigated computationally using density functional theory (DFT) at the B3LYP level employing the DZVP basis set. Optimized structures and the free energy changes associated with ligation have been computed. A good correlation was obtained between the experimental reaction efficiencies and the calculated free energies of bonding. Also, results are presented for the potential energy surfaces for the conversion of the “charge solvated” forms into the “metal salt” forms of CuGly + and AgGly + and of their adducts with CO or NH 3 . The computations indicate a modest catalytic effect of the CO and NH 3 on this conversion.
- Published
- 2003
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37. Threshold Collision-Induced Dissociation Determination and Molecular Orbital Calculations of the Binding Energies of Sodium and Silver Ions to Small Nitrogen-Containing Ligands
- Author
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Christopher F. Rodriquez, Houssain El Aribi, Tamer Shoeib, K. W. Michael Siu, Yun Ling, and and Alan C. Hopkinson
- Subjects
chemistry.chemical_compound ,Benzonitrile ,chemistry ,Collision-induced dissociation ,Methylamine ,Inorganic chemistry ,Binding energy ,Ab initio ,Physical chemistry ,Physical and Theoretical Chemistry ,Ethylamine ,Acetonitrile ,Dissociation (chemistry) - Abstract
The binding energies at 0 K of sodium and silver ions to ammonia, methylamine, ethylamine, acetonitrile, and benzonitrile were determined using threshold collision-induced dissociation (CID) and molecular orbital calculations at the ab initio and density functional theory levels. There is good agreement between experimental and calculated binding energies. For the five ligands, threshold CID/CCSD(t)(fu)/6-311++G(2df,p)//MP2(fu)/6-311++G(d,p) Na+ binding energies are the following: ammonia, 25.6 ± 2.8/24.8; methylamine, 27.0 ± 1.4/25.9; ethylamine, 27.7 ± 2.3/27.1; acetonitrile, 30.0 ± 2.3/30.3; and benzonitrile, 32.7 ± 1.4/35.0 (B3LYP/6-311++G(d,p)//B3LYP/6-311++G(d,p)) kcal/mol. Threshold CID and B3LYP/DZVP Ag+ binding energies are the following: ammonia, 40.6 ± 3.0/38.9; methylamine, 41.5 ± 2.3/41.1; ethylamine, 42.9 ± 1.4/43.2; acetonitrile, 40.8 ± 2.0/39.3; and benzonitrile, 41.5 ± 2.8/43.1 kcal/mol. Wherever comparisons with literature data are possible, the Na+ binding energies determined in this ...
- Published
- 2002
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38. Silver Ion Binding Energies of Amino Acids: Use of Theory to Assess the Validity of Experimental Silver Ion Basicities Obtained from the Kinetic Method
- Author
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Tamer Shoeib, Alan C. Hopkinson, and K. W. Michael Siu
- Subjects
chemistry.chemical_classification ,Denticity ,Inorganic chemistry ,Dissociation (chemistry) ,Ion ,Amino acid ,chemistry.chemical_compound ,Crystallography ,chemistry ,Side chain ,Density functional theory ,Carboxylate ,Proline ,Physical and Theoretical Chemistry - Abstract
The complexes of silver ion, Ag+, with the twenty naturally occurring amino acids have been calculated using hybrid density functional theory at the B3LYP/DZVP level. For all of these silver complexes, several possible structures were examined, but as there are remarkable similarities between all the structures at the global minima, only summarized data are reported. All of the complexes, except that with proline, are solvated ions. Amino acids containing only hydrocarbon side chains are bidentate, coordinating through the amino and carbonyl groups and the remaining amino acids (with the exception of proline) are tricoordinate with the same two interactions as in the simpler amino acids and an additional interaction through the side chain. The proline complex contains zwitterionic proline with the Ag+ ion attached to the carboxylate anion. Enthalpies (at 298 K) for dissociation of Ag+ from the complexes range from 49.3 kcal mol-1 for glycine to 80.4 kcal mol-1 for arginine. Free energies for these reactio...
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- 2002
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39. Binding Energies of the Silver Ion to Small Oxygen-Containing Ligands: Determination by Means of Density Functional Theory and Threshold Collision-Induced Dissociation
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Houssain El Aribi, K. W. Michael Siu, and Alan C. Hopkinson, Yun Ling, Tamer Shoeib, and Christopher F. Rodriquez
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chemistry.chemical_compound ,Collision-induced dissociation ,Computational chemistry ,Chemistry ,Binding energy ,Physical chemistry ,Density functional theory ,Methanol ,Lithium ion binding ,Physical and Theoretical Chemistry ,Diethyl ether ,Sodium ion binding ,Dissociation (chemistry) - Abstract
The binding enthalpies at 0 K of the silver ion to water, methanol, ethanol, diethyl ether, and acetone were calculated using density functional theory (DFT) using the hybrid B3LYP level of theory with the DZVP basis set; they were also measured using the threshold collision-induced dissociation (CID) method. There is good agreement between the two sets of data. For the five ligands, the DFT/threshold CID values are: water, 28.1/31.6 ± 2.5; methanol, 30.1/33.0 ± 3.7; ethanol, 32.0/33.9 ± 3.5; diethyl ether, 33.3/33.2 ± 1.5; and acetone, 36.2/38.0 ± 1.4 kcal/mol. The average of the absolute differences between the DFT and threshold CID results is 2.0 kcal/mol, a value smaller than the average experimental uncertainty of 2.5 kcal/mol. For identical ligands, the silver ion binding energies are lower than the lithium ion binding energies, but higher than the sodium ion binding energies.
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- 2002
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40. Collision-Induced Dissociation of the Ag+−Proline Complex: Fragmentation Pathways and Reaction MechanismsA Synergy between Experiment and Theory
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K. W. Michael Siu, and Alan C. Hopkinson, and Tamer Shoeib
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Fragmentation (mass spectrometry) ,Deuterium ,Collision-induced dissociation ,Chemistry ,Materials Chemistry ,Proline ,Physical and Theoretical Chemistry ,Photochemistry ,Tandem mass spectrometry ,Dissociation (chemistry) ,Surfaces, Coatings and Films ,Ion - Abstract
Gas-phase collision-induced dissociation of the Ag+-proline complex shows six major product ions. Tandem mass spectrometry reveals that at least three of the fragment ions are formed directly from the complex. These are a cyclic immonium ion, formed after elimination of AgH from the Ag+-proline complex, another cyclic immonium ion formed after the elimination of both AgH and CO2, and finally an ion formed as the product of a reductive-elimination reaction in which H2 is lost as a neutral. Selective and nonselective deuterium labeling experiments and hybrid density functional calculations have been employed to probe fragmentation mechanisms that account for all experimental results. The mechanisms for the competitive losses of AgH and H2 from the Ag+-proline complex have been calculated at B3LYP/DZVP.
- Published
- 2001
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41. Characterization of the product ions from the collision-induced dissociation of argentinated peptides
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Christopher F. Rodriquez, Tai-Chu Lau, Ivan K. Chu, Tamer Shoeib, Xu Guo, K. W. Michael Siu, and Alan C. Hopkinson
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Glycylglycine ,Silver ,Collision-induced dissociation ,Tetracoordinate ,010401 analytical chemistry ,Analytical chemistry ,010402 general chemistry ,Tandem mass spectrometry ,01 natural sciences ,Mass Spectrometry ,0104 chemical sciences ,Ion ,chemistry.chemical_compound ,Crystallography ,chemistry ,Fragmentation (mass spectrometry) ,Structural Biology ,Qualitative inorganic analysis ,Density functional theory ,Peptides ,Spectroscopy - Abstract
Tandem mass spectrometry performed on a pool of 18 oligopeptides shows that the product ion spectra of argentinated peptides, the [b n + OH + Ag]+ ions and the [y n − H + Ag]+ ions bearing identical sequences are virtually identical. These observations suggest strongly that these ions have identical structures in the gas phase. The structures of argentinated glycine, glycylglycine, and glycylglycylglycine were calculated using density functional theory (DFT) at the B3LYP/DZVP level of theory; they were independently confirmed using HF/ LANL2DZ. For argentinated glycylglycylglycine, the most stable structure is one in which Ag+ is tetracoordinate and attached to the amino nitrogen and the three carbonyl oxygen atoms. Mechanisms are proposed for the fragmentation of this structure to the [b2 + OH + Ag]+ and the [y2 − H + Ag]+ ions that are consistent with all experimental observations and known calculated structures and energetics. The structures of the [b2 − H + Ag]+ and the [a2 − H + Ag]+ ions of glycylglycylglycine were also calculated using DFT. These results confirm earlier suggestions that the [b2 − H + Ag]+ ion is an argentinated oxazolone and the [a2 − H + Ag]+ an argentinated immonium ion.
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- 2001
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42. Formation of [M − nH + mNa](m−n)+ and [M − nH + mK](m−n)+ ions in electrospray mass spectrometry of peptides and proteins
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K. W. Michael Siu, Tamer Shoeib, Christopher F. Rodriquez, Xu Guo, and Alan C. Hopkinson
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Formamide ,Spectrometry, Mass, Electrospray Ionization ,Reaction mechanism ,Potassium Compounds ,Stereochemistry ,Sodium ,chemistry.chemical_element ,Sodium Chloride ,010402 general chemistry ,Mass spectrometry ,01 natural sciences ,Medicinal chemistry ,Potassium Chloride ,chemistry.chemical_compound ,Acetic acid ,Structural Biology ,Hydroxides ,Sodium Hydroxide ,Qualitative inorganic analysis ,Ubiquitins ,Spectroscopy ,010401 analytical chemistry ,Proteins ,Alkali metal ,0104 chemical sciences ,Models, Chemical ,chemistry ,Mass spectrum ,Indicators and Reagents ,Peptides - Abstract
The [M − nH + mNa](m−n)+ and [M − nH + mK](m−n)+ ions are common in the electrospray mass spectra of proteins and peptides. The feasibility of forming these ions in the gas phase via collision activation and/or ion-molecule reaction is investigated. Sodium and potassium affinities of the N-methylacetamide anion, the acetate anion, and the 1-propanamide anion have been calculated using density functional theory at the B3LYP/6-311+ +G(d,p) level of theory. These anions were chosen as models for the functional groups on a protein or peptide. These affinity values are then used to calculate reaction enthalpies of alkali hydroxides, chlorides, and hydrates with N-methylacetamide, acetic acid, the acetate anion, and 1-propanamine, model reactions that may lead to formation of the [M − nH + mNa](m−n)+ and [M − nH + mK](m−n)+ ions. It is found that a number of these reactions are exothermic or slightly endothermic (ΔH 0 < + 20 kcal/mol) and are accessible after collision activation in the lens region. The potential energy hypersurfaces of model reactions between NaOH and formamide as well as NaCl and formamide show relatively flat surfaces devoid of significant barriers.
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- 2000
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43. A study of complexes Mg(NH3)n+· and Ag(NH3)n+, where n = 1–8: competition between direct coordination and solvation through hydrogen bonding
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Vitali V. Lavrov, Gregory K. Koyanagi, Tamer Shoeib, Alan C. Hopkinson, Rebecca K. Milburn, Diethard K. Bohme, and K. W. Michael Siu
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Collision-induced dissociation ,Hydrogen bond ,Chemistry ,Coordination number ,Enthalpy ,Solvation ,Condensed Matter Physics ,Dissociation (chemistry) ,Adduct ,Crystallography ,Computational chemistry ,Molecule ,Physical and Theoretical Chemistry ,Instrumentation ,Spectroscopy - Abstract
Density functional calculations at B3LYP/6-31+G(d) and B3LYP/DZVP are reported for Mg(NH 3 ) n +· , where n = 1–6 and for some solvated ions Mg(NH 3 ) n +· … NH 3 ( n = 1–3, 6). After correction for basis set superposition errors, the enthalpies for sequential addition of NH 3 to Mg +· resulting from direct coordination to the metal are 38.1, 26.6, 21.2, 13.7, 12.1, and 11.3 kcal mol −1 . The free energies for these same addition reactions are all negative, although for complexes with n ≥ 4 the values are very small. Attempts at optimising structures with higher coordination numbers all resulted in the formation of solvated octahedral complexes. Enthalpies for solvation through hydrogen bonding to one of the ligated NH 3 molecules are all less than 16 kcal mol −1 and decrease rapidly as the number of ligated NH 3 molecules increases. Molecular orbital calculations at B3LYP/DZVP have been used to optimise structures for ions Ag(NH 3 ) n + , where n = 1–6. The five-coordinate and six-coordinate structures have very small binding enthalpies (4.3 and 2.6 kcal mol −1 ) and the free energies for formation of these ions are positive. The binding energies for the addition of the first and second NH 3 molecules added to Ag + are 40.1 and 36.1 kcal mol −1 , while those for the third and fourth additions are much smaller (15.1 and 11.0 kcal mol −1 ). Adducts up to n = 3 have been detected in electrospray experiments. The first three adducts of Ag + with NH 3 have been formed in the selected ion flow tube apparatus and multicollision induced dissociation experiments show Ag(NH 3 ) 3 + to have a lower binding enthalpy than both Ag(NH 3 ) 2 + and Ag(NH 3 ) + .
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- 2000
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44. Comparison between Protonation, Lithiation, and Argentination of 5-Oxazolones: A Study of a Key Intermediate in Gas-Phase Peptide Sequencing
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Christopher F. Rodriquez, Tamer Shoeib, Alan C. Hopkinson, K. W. Michael Siu, and Ivan K. Chu
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chemistry.chemical_compound ,Isodesmic reaction ,Proton ,Chemistry ,Stereochemistry ,Heteroatom ,Proton affinity ,Protonation ,Molecular orbital ,Physical and Theoretical Chemistry ,Medicinal chemistry ,Standard enthalpy of formation ,Methyl group - Abstract
Molecular orbital calculations at B3LYP/6-31++G(d,p) are reported for bases 2-(aminomethyl)-5-oxazolone, 2-(aminomethyl)-4-methyl-5-oxazolone, 2-phenyl-5-oxazolone, and 2-phenyl-4 methyl-5-oxazolone and for the cations formed by protonation of these bases on their imino nitrogens. Structures and relative energies for isomers generated by protonation at each of the four heteroatoms of 2-(aminomethyl)-5-oxazolone are reported. Lithium and silver cations both add to 2-(aminomethyl)-5-oxazolone, but unlike the proton, they bind with two heteroatoms simultaneously. For both the lithiated and argentinated 2-(aminomethyl)-5-oxazolone cations the lowest energy isomers have the metal coordinated with the two nitrogen atoms. Proton affinities of these bases are in the range 217.0-221 kcal mol -1 , with the methyl group at C4 increasing the proton affinity by 3 kcal mol -1 . Single-point calculations were performed at MP4(fc)/6-311++G(2df,p)//B3LYP/6-31++G(d,p) for 2-(aminomethyl)-5-oxazolone, diketopiperazine, glycine, and alanine and their conjugate acids. The proton affinities from this level of theory are lower by as much as 2.7 kcal mol -1 than those calculated at B3LYP/6-31++G(d,p). Enthalpies of formation calculated at B3LYP/6-31++G(d,p) from isodesmic reactions for glycine, alanine, and their conjugate acids are all within 1 kcal mol -1 of the experimental values, but those calculated at MP4 deviate by as much as 4.8 kcal mol -1 . Enthalpies of formation from atomization reactions at the MP4 level are in larger disagreement with experimental values.
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- 2000
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45. Solvent-Assisted Rearrangements between Tautomers of Protonated Peptides
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Ivan K. Chu, Tamer Shoeib, K. W. Michael Siu, Alwin Cunje, Christopher F. Rodriquez, and and Alan C. Hopkinson
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Solvent ,Formamide ,Bond length ,chemistry.chemical_compound ,Chemistry ,Stereochemistry ,Amide ,Molecule ,Peptide bond ,Protonation ,Physical and Theoretical Chemistry ,Medicinal chemistry ,Tautomer - Abstract
The presence of an interacting water or methanol molecule has been shown to catalyze the 1,3-proton shift in a peptide linkage between the tautomers of protonated formamide and glycylglycylglycine. Density functional theory calculations at the B3LYP/6-31++G(d,p) level of theory show that, for glycylglycylglycine, the forward barrier of this shift decreases from a free energy at 298 K of 39.6 kcal/mol in the absence of solvent to 26.7 kcal/mol in the presence of water and to 22.0 kcal/mol in the presence of methanol. Protonation at the amide nitrogen of the second residue results in a large increase in the C -N bond distance from 1.336 to 1.519 A, whereas protonation at the carbonyl oxygen leads to a decrease in the C-N bond distance from 1.336 to 1.321 A. Solvent-catalyzed tautomerism may play an important role in the fragmentation of electrosprayed, protonated peptides in the gas phase.
- Published
- 2000
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46. Oxaliplatin complexes with carnosine and its derivatives: in vitro cytotoxicity, mass spectrometric and computational studies with a focus on complex fragmentation
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Ahmed S. Youssef, Helen J. Reid, Tamer Shoeib, Barry L. Sharp, Eslam M. Moustafa, Asma Amleh, and Claire L. Camp
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Dipeptide ,Organoplatinum Compounds ,Cell Survival ,Stereochemistry ,Ligand ,Carnosine ,Electrospray ionization ,Anserine ,Metals and Alloys ,Biophysics ,Protonation ,Hep G2 Cells ,Biochemistry ,Affinities ,Mass Spectrometry ,Oxaliplatin ,Biomaterials ,chemistry.chemical_compound ,chemistry ,Chemistry (miscellaneous) ,Humans ,Cytotoxicity ,Antineoplastic Agents, Alkylating - Abstract
The complexation of the Pt-based anti-cancer drug oxaliplatin (OxPt) with biological ligands other than DNA is believed to be a major cellular sink for the drug reducing its therapeutic potential and acting as a potential cause of toxicity. In this paper, the very first hypothesis driven investigation of the role of the naturally abundant cytoplasmic dipeptide ligand β-alanyl-l-histidine dipeptide (carnosine) in OxPt detoxification is presented. In vitro studies on hepatocellular carcinoma HepG2 cells suggest that carnosine may inhibit the cytotoxic action of OxPt most likely through the formation of complexes that are less cytotoxic than OxPt alone. Evidence is provided to suggest that pre-exposure of HepG2 cells to elevated levels of carnosine appears to have a lasting effect on reducing the cytotoxicity of OxPt even after the removal of the externally added carnosine. This effect, however, is likely under kinetic control as its magnitude was shown not to vary significantly with the level of carnosine exposure within the concentration range used in this study. Various mass spectrometry techniques employing electrospray ionization and chip nanospray were employed to study the interaction of oxaliplatin with carnosine as well as two of its derivatives β-alanyl-N-methylhistidine (anserine) and N-acetylcarnosine (NAC). Evidence of complexation between OxPt and each of the three ligands examined is presented. Most species observed were unambiguously assigned and compared to their theoretical isotopic patterns. Common fragmentation products due to the collisionally-activated protonated complexes of each of the ligands examined with OxPt, [M + OxPt + H](+), where M = carnosine, anserine or NAC, were reported. Density functional calculations at the B3LYP/LANL2DZ level were used to obtain structural information and relative free energies of different isomers of the observed precursor [Carnosine + OxPt + H](+) both in the gas phase and in solution as well as to probe its fragmentation, highlighting plausible fragmentation mechanisms that account for all the experimental results. Data are presented to show several binding modes between electron rich sites such as N and O centers of carnosine and the Pt metal of OxPt. Calculations were also employed to obtain proton affinities and free energies of key reactions. The proton affinities of carnosine, anserine and NAC at 298 K were calculated to be 254.4, 255.9 and 250.2 kcal mol(-1) respectively. To the best of our knowledge the proton affinities of anserine and N-acetyl-carnosine are the first reported values in the literature.
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- 2013
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47. Gas-phase fragmentation of the Ag+–phenylalanine complex: cation–π interactions and radical cation formation
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Alwin Cunje, Alan C. Hopkinson, K. W. Michael Siu, and Tamer Shoeib
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Models, Molecular ,Spectrometry, Mass, Electrospray Ionization ,Electrospray ,Silver ,Free Radicals ,Phenylalanine ,Analytical chemistry ,010402 general chemistry ,Mass spectrometry ,01 natural sciences ,Dissociation (chemistry) ,Ion ,Fragmentation (mass spectrometry) ,Structural Biology ,Cations ,Spectroscopy ,Chemistry ,010401 analytical chemistry ,Deuterium ,0104 chemical sciences ,Radical ion ,Isotope Labeling ,Physical chemistry ,Indicators and Reagents - Abstract
Collision-induced dissociation experiments on the Ag+–phenylalanine complex using several collision energies were shown to yield ten different fragment ions. Unambiguous assignment of these fragment ions were made by careful analysis of deuterium labeling experiments. The losses of H2O, CO, CO2, and AgH were commonly observed; also encountered were the losses of H2, Ag, and H. Deuterium labeling experiments and density functional calculations have been employed to probe fragmentation mechanisms that account for all experimental results.
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48. A study on the physicochemical properties and cytotoxic activity of p-sulfocalix[4]arene-nedaplatin complex.
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Sherif Ashraf Fahmy, Jana Brüßler, Fortuna Ponte, Mohamed K Abd El-Rahman, Nino Russo, Emilia Sicilia, Udo Bakowsky, and Tamer Shoeib
- Published
- 2019
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