Search

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

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.

In this study, two environmentally-friendly macroscopically formal (PVF) composited sponges (PL and PLS) functionalized with lignin and lignosulfonate, respectively, were fabricated by a one-step mechanical foaming method. PLS possessed the largest specific surface area of approximately 22.396 m2/g, a three-dimensional skeleton structure with a skeletal density of 3.236 g/cm3, and 0.338 mmol/g of acidic oxygen-containing groups. Thus, it showed the highest adsorption capacity of 0.16–0.24 mmol/g (51.17–76.75 mg/g) in removing seven antibiotics, of the popular fluoroquinolones (FQs) family from water. The contributions of hydrogen bonding, electrostatic attraction (EA) and π-π electron donor-acceptor interaction to the adsorption of FQs onto the PL and PLS sponges were analyzed systematically by investigating the pH dependence of the adsorption capacity, and the changes in adsorption of two sub structural analogs of FQs as molecular probes, and by performing theoretical calculations. The EA between the acidic oxygen-containing groups on the sponges and the amino groups of FQs played a dominant role in adsorption in near neutral conditions, leading to a superior adsorption performance for PLS. Overall, the composited sponges have the advantages of simple production, environmental-friendliness, convenient recycle, and low cost, which renders them potentially viable in treating real wastewater containing FQs.

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.

Choline is a quaternary ammonium bioactive compound that is used as a dietary supplement. Direct determination of choline in pharmaceutical formulations is a challenging analytical task. The strong UV absorbance of p-sulfonatocalix[4]arene (SC4) and its outstanding complexation properties towards quaternary ammonium compounds have been utilized to develop a method to detect and quantify choline in aqueous solution. This method has been applied to a commercial pharmaceutical choline formulation showing results with no statistically significant difference from those obtained by the official U.S. Pharmacopeial method. The method was validated according to ICH guidelines and the limit of detection for choline was calculated to be 7.2 × 10−6 mol L−1 (1.30 μg mL−1). The host-guest complexation between SC4 and choline were investigated using UV and 1H NMR spectroscopy and DFT calculations. The peak amplitude of the host-guest complexes formed were found to be linearly proportional to the concentration of the choline and l -carnitine analytes in the ranges of 1.0 × 10−5 to 1.6 × 10−4 mol L−1 and 1.0 × 10−5 to 1.8 × 10−4 mol L−1 respectively. The reaction stoichiometry between either choline or l -carnitine with SC4 in the formed complexes were determined to be 1:1 while the stability constants for the complexes formed were estimated to be 8.3 × 104 M−1 and 2.8 × 104 M−1 in the case of choline and l -carnitine, respectively. Both 1H NMR spectroscopy and DFT calculations suggest the complexation between choline and SC4 involves the insertion of the trimethylammonium group of choline into the cavity of SC4 in agreement with previously published X-ray data. The spectrophotometric method presented here should not be limited to the determination of choline. The linear relationship between the peak amplitude of the host-guest complex formed between SC4 and l -carnitine presented here suggests the applicability of the method for the detection of other small molecular species possessing a quaternary ammonium group.

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.

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. In this paper the first experimental and theoretical investigation of 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 is presented. Data from 1H NMR, UV, Job's plot analysis, HPLC 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 which may allow for this strategy to be effective for potential use in drug delivery.

The occurrence and concentrations of six common phthalates were investigated for the first time in bottled water locally produced in the Egyptian market. The compounds investigated were dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), n-butyl benzyl phthalate (BBP), diethyl hexyl phthalate (DEHP), and Di-n-octyl phthalate (D-n-OP). A set of 108 bottled water samples from six different commercial brands of water bottled in transparent polyethylene terephthalate (PET) plastic bottles with high density polyethylene (HDPE) plastic caps were investigated. Water samples were analyzed immediately after purchasing (~2weeks after production), after being stored at room temperature (25±5°C), in a refrigerator (4±1°C) and outdoor under sun exposure (daylight temperature of 40±5°C). Samples were stored up to six months depending on the tested condition. Among the target compounds, only DEHP and DBP were detected in the samples analyzed immediately after purchasing with a detection frequency of 50 and 58% and mean concentrations of 0.104 and 0.082μgl-1 respectively. Significant positive correlation was obtained between the storage time, temperature and the concentration of phthalate compounds detected in the bottled water, indicating possible migration from the PET plastic material as the source. The estimated contribution of bottled water consumption to the tolerable daily intake (TDI) levels of the two most abundant phthalates observed here for adults and toddlers did not exceed 0.16 and 0.72% for DBP while these values were 0.04 and 0.16% for DEHP respectively. These estimated daily intake values from PET bottled water consumption were far below their respective TDI values and therefore should constitute no adverse health effects.

l

The preoxidation effects of H

Choline (Ch+), is a vitamin-like essential water-soluble organic micronutrient. The US-FDA requires that infant formula not made from cow's milk must be supplemented with Ch+. Direct determination of Ch+ in milk powders and infant formulas is a challenging task due to the lack of a detectable chromophore, its existence in free and complexed forms as well as the presence of multi-analytes in these complex matrices. Here, an enzyme-free potentiometric ion selective electrode (ISE) with high selectivity for Ch+, a linear range from 0.03 μM up to 1 mM, a 0.061 μM detection limit (LOD) and a typical response time less than 5 and no greater than 60 s is developed for monitoring of Ch+ in infant formula and milk powders. To achieve these ISE parameters we relied on the ability of calixarenes and its derivatives to form host-guest complexes with the positively charged quaternary ammonium moiety of Ch+. We employed a lipophilic (membrane-compatible) calixarene as an ionophore in the sensing membrane phase to provide a molecular receptor for Ch+ capable of selective binding; while utilizing, hydrophilic (water-soluble) p-sulfonated calixarene as a buffering agent to optimize the inner filling solution to reduce transmembrane Ch+ fluxes. All the calixarene structures and their complexes with Ch+ were optimized at the density functional theory (DFT) level and the Gibbs free energies for the inclusion of Ch+ into the calixarenes were calculated. The prepared sensor was shown to selectively respond only to Ch+ in the presence of all other interferents in the tested matrices with results that are not statistically significantly different for either accuracy or precision relative to the much more laborious official AOAC 1999 coupled enzymatic–spectrophotometric method. The proposed method is highly selective, non-enzymatic, requires no derivatization or incubation steps, offers a fast response time, and has the potential of portability for in situ analysis, while being relatively cost effective and non-laborious.

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.

There are very few studies reporting concentrations of polybrominated diphenyl ethers (PBDEs) and novel flame retardants (FRs) or non-PBDEs in Africa and the Middle East. The present work reported concentrations of fourteen PBDE congeners and eleven non-PBDE flame retardants in dust samples collected from homes (n=17), workplaces (n=9) and cars (n=5) in the greater Cairo region. The median ∑PBDE concentrations were 57, 425 and 1608 ng g(-1) in homes, workplaces and cars respectively. The highest PBDE levels were observed for BDE 209, with a median concentration of 40.2, 366 and 1540 ng g(-1) representing 70% to 95% of the total PBDEs in homes, workplaces and cars respectively. This is about 8 to 46 times greater than the median concentration of the pentaBDE (represented by the most abundant compounds in this formulation, ∑BDE 47, 99 and 100). In the case of non-PBDE flame retardants, a detection frequency between 52% and 100% was observed for several compounds including: hexabromocyclododecane (HBCD), hexabromobenzene (HBB), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), bis (2-ethyl-1-hexyl) tetrabromophthalate (TBPH), 1,2-bis (2,4,6-tribromophenoxy) ethane (TBPE), ally-2,4,6-tribromophenyl ether (ATE) and Dechlorane Plus (DP). The ∑non-PBDE median concentrations were 8.30, 28.9 and 49.9 ng g(-1) in homes, workplaces and cars respectively with the highest level observed for HBCD in the three microenvironments. The detection of novel flame retardants in indoor environments may be due to their wide usage after the ban of the penta and octa BDE formulation. Results show the levels of PBDEs and non-PBDEs in Egyptian dust to be among the lowest levels reported from other countries. Different dust exposure scenarios using 5th percentile, median, 95th percentile and maximum levels were estimated for adult and children. The estimated dust intake results were several orders of magnitude lower than the oral reference dose values.

For the synthesis and selection of active platinum-based anticancer drugs that perform better than cisplatin and its analogues, six-coordinate octahedral Pt(IV) complexes appear to be promising candidates as, being kinetically more inert and more resistant to ligand substitution than four-coordinate Pt(II) centers, they are able to minimize unwanted side reactions with biomolecules prior to DNA binding. Due to their kinetic inertness, Pt(IV) complexes have also been exploited to bypass inconvenient intravenous administration. The most prominent example is satraplatin (Sat.) which is the first platinum antineoplastic agent reported to have oral activity. The present paper deals with a theoretical DFT investigation of the influence that the acidity of the biological environment can have on the activity of satraplatin and analogous octahedral Pt(IV) complexes having two carboxylates as axial ligands. Moreover, here the outcomes of a joint electrospray ionization mass spectrometry and DFT investigation of the fragmentation pathways of the protonated satraplatin are reported. Calculations show that the simulated acidic environment has an important impact on the satraplatin reactivity causing a significant lowering of the barrier that is necessary to overcome for the hydrolysis of the first acetate ligand to occur. Data from electrospray ionization mass spectrometry

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

Pt-based anti-cancer drugs can form complexes with biological ligands other than their intended pharmacological targets. Such complexes are believed to be a major contributor to the reduction of the anti-cancer drugs’ therapeutic potential and can act as potential causes of toxicity. Recently, the cytoplasmic ligand β - alanyl-L-histidine dipeptide (carnosine) was shown to act as a sequestering agent for oxaliplatin (OxPt) inhibiting its cytotoxic action most likely through the formation of complexes that are less cytotoxic than OxPt alone. In this paper, the calculated binding modes and binding energies of protonated carnosine as well as canosine complexes with various biologically relevant metal cations and some common Pt-based anti-cancer drugs both in the gas phase and in solution are presented. Theoretical evidence for the existence of protonated carnosine in a zwitterionic form is offered. Six calculated geometrical arrangements comprising general structural motifs of metal ion-carnosine complexes are presented. In all but one of these six conformers the metal ions were shown to form three bonds to each of the carnosine ligands. These six general binding motifs were found to cover the lowest energy structures of all species investigated here whether in the gas phase or in solution. The data presented increases our knowledge of the interactions of carnosine with different metals, either those naturally found inside the body or those that are up taken via foods, supplements or drugs.

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.

A detailed structural analysis of the complexes resulting from the association of the neutral, mono- and di-anionic forms cytoplasmic thiol containing tripeptide glutathione (GSH) to the post water substituted hydrolysed form of the anti-cancer drug cisplatin, [Pt(NH 3 ) 2 ] 2+ , in the gas phase and in solution is presented. These structures which are formed from a 1:1 molar ratio of the glutathione ligand and the Pt-drug, have been proposed as possible intermediates for several postulated disulfide bridged polymeric species. Ten gas phase structures on the [GSH − H + Pt(NH 3 ) 2 ] + potential energy surface are presented and the coordination of the Pt metal is discussed. The [GSH + Pt(NH 3 ) 2 ] 2+ potential energy surface was also explored and twelve gas phase structures on this surface are presented. In order to describe the complexes examined here in solution, water solvation effects were considered for eight and nine of the most energetically favored structures of the [GSH − H + Pt(NH 3 ) 2 ] + and [GSH + Pt(NH 3 ) 2 ] 2+ potential energy surfaces, respectively. The enthalpy and free energy, based on the most thermodynamically favored conformers of the reactants and products, for the addition reaction [Pt(NH 3 ) 2 ] 2+ + [GSH − H] − → [GSH − H + Pt(NH 3 ) 2 ] + in the gas phase at 298 K were determined to be −331.8 and −314.8 kcal mol −1 , respectively. Similarly, the enthalpy and free energy of the gas phase reaction [Pt(NH 3 ) 2 ] 2+ + GSH → [GSH + Pt(NH 3 ) 2 ] 2+ at 298 K were determined to be −185.0 and −167.4 kcal mol −1 .

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.

The fragmentations of [AA + M](+) complexes, where AA = Phe, Tyr, Trp, or His, and M is a monovalent metal (Li, Na, or Ag), have been exhaustively studied through collision-induced dissociation (CID) and through deuterium labeling. Dissociations of the Li- and Ag-containing complexes gave a large number of fragment ions; by contrast, the sodium/amino acid complexes have lower binding energies, and dissociation resulted in much simpler spectra, with loss of the entire ligand dominating. Unambiguous assignments of these fragment ions were made and formation mechanisms are proposed. Of particular interest are fragmentations in which the charge was retained on the organic fragment and the metal was lost, either as a metal hydride (AgH) or hydroxide (LiOH) or as the silver atom (Ag(•)).

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.

Positive mode electrospray mass spectrometry was used to investigate complexes of cysteine and selenocysteine with the metallo-drug Auranofin and the analogous chlorotriethylphosphine gold. Evidence for all the complexes, with the exception of the Auranofin–selenocysteine complex, was obtained. Several fragmentation products were examined and their proposed structures reported. Structural details of many experimentally observed ions including [Auranofin + H] + , [(CH 3 CH 2 ) 3 P–Au–cysteine] + and [(CH 3 CH 2 ) 3 P–Au–methylselenocysteine] + were examined by means of hybrid density functional theory at the B3LYP/DZVP level. Structural information and relative free energies are presented for several isomers of each ion considered.

The complexes of Ag + with the peptides MetGly, ProGly, GlyPro, GlyHis and GlyProAla were investigated using hybrid density functional theory at the B3LYP/DZVP level. The silver ion binding free energies at 298 K to each of these peptides was calculated to be 60.8, 52.0, 54.3, 71.2 and 63.3 kcal mol −1 , respectively. Structural information and relative free energies are presented for several isomers for each of the five complexes. Each of the global minima found for the five complexes is a charge-solvated ion. An important finding is that the Ag + –ProGly is the only complex where a salt bridge structure is energetically favored occurring at 4.0 kcal mol −1 higher in free energy than the global minimum. The Ag + ion in this salt bridge structure is attached to the carboxylate anion of zwitterionic ProGly in which the terminal amino nitrogen is protonated. For all the other complexes studied, the salt bridge structure occurs at much higher energies. All the dipeptide complexes with Ag + , but one, exhibit a di- or tri-coordinate metal where the sites of attachment are amino and carbonyl groups. However, the highest coordination numbers are not always the global minima due to steric costs. The global minimum of the Ag + –GlyProAla complex is the only structure found in this study where the metal is tetra-coordinated, binding to the terminal amino nitrogen and all three carbonyl oxygen atoms. Silver binding to sulphur and imidazole nitrogen atoms of MetGly and GlyHis, respectively, are present in the three most energetically favored species in each of these cases.