Search

In the present manuscript, three different 4,7-dihydroxycoumarin derivatives were prepared and structurally characterized by crystallographic and spectroscopic techniques in combination with the B3LYP-D3BJ theoretical method. Cytotoxic and antimicrobial activities of investigated compounds were screened against different cell lines and microorganisms. HCT-116 cells were most sensitive to the 3-(1-(2-hydroxyphenyl)amino) ethylidene)-2,4-dioxochroman-7-yl acetate derivative, while the best antimicrobial activity against Bacillus subtilis ATCC 6633 was shown by 3-(1-(2-hydroxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate. The molecular docking study for all compounds with important epidermal growth factor receptors (EGFR) was performed. The results indicate that the largest contribution to the binding energy is through conventional hydrogen bonds.

Ruthenium complexes have gained significant attention due to the ruthenium similarity to iron, lower toxicity, and higher anticancer effectiveness than other compounds. In this contribution, five new isonicotinate-polyethylene glycol ester ligands were synthesised and characterised by NMR and IR spectroscopies. The corresponding Ru(II) complexes were also obtained, and their structure was investigated by traditional methods. The optimisation of structures was performed at B3LYP/6-31+G(d,p) level of theory for H, C, N and O atoms and B3LYP/LanL2DZ for Ru. The intramolecular stabilisation interactions were assessed through the natural bond orbital approach. The NMR chemical shifts were predicted by the gauge independent atomic orbital method and compared to the experimental values. High correlation coefficients and low mean absolute errors between these data sets proved that the predicted structures described well the experimental ones. The theoretical and experimental IR spectra were also compared, and differences in the most notable bands were described. One of the ligands (L5) and complexes (5) showed fluorescent properties due to methylisatoic moiety. The electronic spectra of this compound were modelled by the time dependent-density functional theory method. The difference of 11 nm between the experimental and the theoretical wavelength was explained by the interactions between the solvent and the solute. Further biological and theoretical studies are advised for this series of compounds.

Organotin(IV) compounds show great potential as antitumor metallodrugs with lower toxicity and higher antiproliferative activity. Histone deacetylases (HDAC) inhibitors are characterised by high bioavailability and low toxicity. In this research, the two novel octahedral organotin(IV) complexes of physiologically active hydroxamate-based ligands, N-hydroxy-4-phenylbutanamide (HL1) and N-hydroxy-2-propylpentanamide (HL2), have been prepared and characterized using FTIR, 1H-, 13C- and 119Sn-NMR spectroscopy. Particular emphasis was put on the binding characteristics of ligands. The structures were additionally analysed by the density functional theory at B3LYP-D3BJ/6- -311++G(d,p)(H,C,N,O)/LanL2DZ(Sn) level. The theoretical IR and NMR spectra were compared to the spectroscopic data, and it was concluded that the predicted structures described well the experimental ones. The stability of different isomers of HL1 and HL2 was assessed by the natural bond orbital analysis, and the importance of intramolecular hydrogen bond was outlined. The interactions between donor atoms and Sn were investigated and correlated with the changes in chemical shift and the wavenumbers of characteristic vibrations.

Objectives: New tributyltin(IV) complexes containing the carboxylate ligands 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoic acid (HL1) and 2-(4-methyl-2-oxoquinolin-1(2H)-yl)acetic acid (HL2) have been synthesized. Methods: Their structures have been determined by elemental microanalysis, FT-IR and multinuclear NMR (1H, 13C and 119Sn) spectroscopy and X-ray diffraction study. A solution state NMR analysis reveals a four-coordinated tributyltin(IV) complex in non-polar solvents, while an X-Ray crystallographic analysis confirms a five-coordinated trigonal-bipyramidal geometry around the tin atom due to the formation of 1D chains. A theoretical structural analysis was performed by optimization employing B3LYP-D3BJ functional and 6-311++G(d,p)/def2-TZVP(Sn) basis sets for H, C, N, O/Sn, respectively. The interactions between tin(IV) and surrounding atoms were examined by QTAIM approach. The in vitro antiproliferative activity of the synthesized compounds was evaluated by MTT and CV assays versus MCF-7 (human breast adenocarcinoma), HCT116 (human colorectal carcinoma), A375 (human melanoma), 4T1 (mouse breast carcinoma), CT26 (mouse colon carcinoma) and B16 (mouse melanoma) tumor cell lines. Results: Both synthesized compounds (nBu3SnL1 and nBu3SnL2) exerted powerful micromolar IC50 cytotoxicity values and demonstrated high selectivity toward malignant cells. Both experimental drugs affected cell adhesion and induced anchorage independent apoptosis, a favorable type of cell death with an essential role in cancer dissemination prevention. The BSA-binding affinity of the obtained organotin compounds was followed by spectrofluorometric titration and molecular docking simulations. Conclusions: The tributyltin(IV) compounds selectively induce anoikis-like cell death in A375 cells, also highlighting the importance of the organic moiety on the tin(IV) ion in the mechanism of action. [ABSTRACT FROM AUTHOR]

Copper–semicarbazone ligands have been extensively investigated for several medicinal applications. In this contribution, a novel copper(II) complex with a pyridoxal–semicarbazone ligand, [Cu(PLSC)Cl(H2O)](NO3)(H2O), was synthesized and characterized by X-ray crystallography, elemental analysis, UV-VIS, and FTIR spectroscopies. The stabilization interactions within the structure were assessed using the Hirshfeld surface analysis. The crystallographic structure was optimized at the B3LYP/6-311++G(d,p)(H,C,N,O)/LanL2DZ(Cu) level of theory. A comparison between the experimental and theoretical bond lengths and angles was undertaken to verify the applicability of the selected level of theory. The obtained high correlation coefficients and low mean absolute errors confirmed that the optimized structure is suitable for further investigating the interactions between donor atoms and copper, along with the interactions between species in a neutral complex, using the Quantum Theory of Atoms in Molecules approach. The electrostatic potential surface map was used to reveal distinct charge distributions. The experimental and calculated FTIR spectra were compared, and the most prominent bands were assigned. The interactions with human serum albumin (HSA) were assessed by spectrofluorometric titration. The spontaneity of the process was proven, and the thermodynamic parameters of binding were calculated. Molecular docking analysis identified the most probable binding site, providing additional insight into the nature of the interactions. [ABSTRACT FROM AUTHOR]

The present research aimed to investigate the demineralizing effects of sulfuric acid on pig bone. Alterations in collagen and phosphate contents and changes in the elemental composition of the bone during the 14-day-long immersion in sulfuric acid solutions of different concentrations were estimated using ATR-FTIR, LIBS, and AAS. FTIR spectra at amide I (1800–1600 cm−1) and phosphate ν1/ν3 (PO43−) (1300–900 cm−1) domains were scrutinized using the deconvolution method for monitoring changes in the protein secondary structure and mineral content. The results implicated sulfuric acid as a powerful demineralization agent and effective in targeting mineral components, such as hydroxyapatite, while leaving the collagen matrix relatively preserved with a complex secondary structure. Collagen maturity marker values gave valuable insights into the structural integrity of the bone. LIBS and AAS indicated changes in bone hardness; phosphorous-to-carbon ratio; and calcium, phosphorous, and magnesium content in the solutions left after the immersion period. The changes in the ratio of ionic-to-atomic calcium lines in the LIBS spectra indicated hardening of the bone, with increasing acid concentration and prolonged action, due to the deposition of calcium sulfate on the surface. The calcium concentration in the solutions decreased with increased acid concentration, while the change in phosphorus and magnesium concentrations was reversed. [ABSTRACT FROM AUTHOR]

Background: The aim of this research is the synthesis and characterization of coumarin-palladium complex and the investigation of the cytotoxicity of both the ligand and the complex. Methods: The palladium(II) complex (CC) was obtained in the reaction between (E)-3-(1-((4-hydroxy-3-methoxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl-acetate (CL) and potassium-tetrachloropalladate(II) and characterized using IR and NMR spectra, experimentally and theoretically. Cytotoxicity of CL and CC were determined for human cervical carcinoma HeLa, ovarian cancer A2780, hormone dependent breast cancer MCF7, and colorectal cancer HCT116 lines. The interaction of investigated compounds with HSA was followed by spectrofluorimetric method. The binding mechanism in the active pocket was assessed via molecular docking simulations. Results: A low mean absolute error between experimental and theoretical data proved that the optimized structure corresponded to the experimental one. Both compounds showed a satisfactory selectivity index towards neoplastic cells. The binding affinity of tested compounds to the HSA were confirmed. The molecular docking showed a much lower change in the Gibbs free energy of binding for CC compared to CL. Conclusions: The obtained results revealed that CL and CC exhibit significant effects on several cancer cell lines and good binding properties to HSA, while molecular docking discovered that CC has the most pronounced activity against alpha-fetoprotein. [ABSTRACT FROM AUTHOR]

The pyridoxal-semicarbazone (PLSC) ligand and its transition metal complexes have shown significant biological activity. In this contribution, a novel nickel(II)-PLSC complex, [Ni(PLSC)(SO4)(H2O)2], was obtained, and its structure was determined by X-ray crystallographic analysis, FTIR, and UV-VIS spectroscopy. The sulfate ion is directly coordinated to the central metal ion. The intermolecular stabilization interactions were examined using Hirshfeld surface analysis. The crystal structure was optimized by a B3LYP functional using two pseudopotentials for nickel(II) (LanL2DZ and def2-TZVP) together with a 6-311++G(d,p) basis set for non-metallic atoms. The experimental and theoretical bond lengths and angles were compared, and the appropriate level of theory was determined. The stabilization interactions within the coordination sphere were investigated by the Quantum Theory of Atoms in Molecules (QTAIM). The antioxidant activity towards hydroxyl and ascorbyl radicals was measured by EPR spectroscopy. The interactions between Human Serum Albumin (HSA) and the complex were examined by spectrofluorimetric titration and a molecular docking study. The mechanism of binding to DNA was analyzed by complex fluorescence quenching, potassium iodide quenching, and ethidium bromide displacement studies in conjunction with molecular docking simulations. [ABSTRACT FROM AUTHOR]

Benzodiazepines are frequently encountered in crime scenes, often mixed with adulterants and diluents, complicating their analysis. This study investigates the interactions between two benzodiazepines, lorazepam (LOR) and alprazolam (ALP), with common adulterants/diluents (paracetamol, caffeine, glucose, and lactose) using infrared (IR) spectroscopy and quantum chemical methods. The crystallographic structures of LOR and ALP were optimized using several functionals (B3LYP, B3LYP-D3BJ, B3PW91, CAM-B3LYP, M05-2X, and M06-2X) combined with the 6-311++G(d,p) basis set. M05-2X was the most accurate when comparing experimental and theoretical bond lengths and angles. Vibrational and 13C NMR spectra were calculated to validate the functional's applicability. The differences between LOR's experimental and theoretical IR spectra were attributed to intramolecular interactions between LOR monomers, examined through density functional theory (DFT) optimization and quantum theory of atoms in molecules (QTAIM) analysis. Molecular dynamics simulations modeled benzodiazepine–adulterant/diluent systems, predicting the most stable structures, which were further analyzed using QTAIM. The strongest interactions and their effects on IR spectra were identified. Comparisons between experimental and theoretical spectra confirmed spectral changes due to interactions. This study demonstrates the potential of quantum chemical methods in analyzing complex mixtures, elucidating spectral changes, and assessing the structural stability of benzodiazepines in forensic samples. [ABSTRACT FROM AUTHOR]

Nickel transition metal complexes have shown various biological activities that depend on the ligands and geometry. In this contribution, six Ni(II) nitrate complexes with pyridoxal-semi, thiosemi, and isothiosemicarbazone ligands were examined using theoretical chemistry methods. The structures of three previously reported complexes ([Ni(PLSC)(H2O)3]∙2NO3−, [Ni(PLTSC)2] ∙2NO3−∙H2O, and [Ni(PLITSC)(H2O)3]∙2NO3−) were investigated based on Hirshfeld surface analysis, and the most important stabilization interactions in the crystal structures were outlined. These structures were optimized at the B3LYP/6-311++G(d,p)(H,C,N,O,(S))/LanL2DZ(Ni) level of theory, and the applicability was checked by comparing theoretical and experimental bond lengths and angles. The same level of theory was applied for the optimization of three additional structures, ([Ni(PLSC)2]2+, [Ni(PLTSC)(H2O)3]2+, and [Ni(PLITSC)2]2+). The interactions between selected ligands and Ni(II) were examined using the Natural Bond Orbital (NBO) and Quantum Theory of Atoms in Molecules (QTAIM) approaches. Particular emphasis was placed on interactions between oxygen, sulfur, and nitrogen donor atoms and Ni(II). Human Serum Albumin (HSA) and the DNA-binding properties of these complex cations were assessed using molecular docking simulations. The presence of water molecules and various substituents in the thermodynamics of the processes was demonstrated. The results showed significant effects of structural parameters on the stability and reactivity towards important biomolecules. [ABSTRACT FROM AUTHOR]

New Cu(II) complexes with pyridoxal-aminoguanidine (PLAG) ligands and different counterions (SO42− and NO3−) were prepared and their crystal structures were solved by the X-ray crystallography. The geometries of the obtained complexes significantly depended on the counterions, leading to the square-pyramidal structure of [Cu(PLAG)NO3H2O]NO3 (complex 1) and square-planar structure of [Cu(PLAG)H2O]SO4 (complex 2). The intermolecular interactions were examined using the Hirshfeld surface analysis. The theoretical structures of these complexes were obtained by optimization at the B3LYP/6-311++G(d,p)(H,C,N,O,S)/LanL2DZ(Cu) level of theory. The Quantum Theory of Atoms in Molecules (QTAIM) was applied to assess the strength and type of the intramolecular interactions and the overall stability of the structures. The interactions between the complexes and transport proteins (human serum albumin (HSA)) and calf thymus DNA (CT-DNA) were examined by spectrofluorometric/spectrophotometric titration and molecular docking. The binding mechanism to DNA was assessed by potassium iodide quenching experiments. The importance of counterions for binding was shown by comparing the experimental and theoretical results and the examination of binding at the molecular level. [ABSTRACT FROM AUTHOR]

This study examined the antiradical activity of three synthesized coumarin derivatives: (E)-3-(1-((2-hydroxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate (A1-OH), (E)-3-(1-((3-hydroxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate (A2-OH), and (E)-3-(1-((4-hydroxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate (A3-OH) against HOO•/O2•− radical species. The investigation included electron spin resonance (ESR) measurements and a DFT kinetic study. Thermodynamic and kinetic parameters of antiradical mechanisms—Formal Hydrogen Atom Transfer (f-HAT), Radical Adduct Formation (RAF), Sequential Proton Loss followed by Electron Transfer (SPLET), and Single-Electron Transfer followed by Proton Transfer (SET-PT)—were evaluated using the Quantum Mechanics-based test for Overall Free Radical Scavenging Activity (QM–ORSA) under physiological conditions. ESR results indicated antiradical activity decreased in the sequence A1–OH (58.7%) > A2–OH (57.5%) > A3–OH (53.1%). Kinetic analysis revealed the f-HAT mechanism dominated HOO• inactivation. A newly formulated Sequential Proton Loss followed by Radical Adduct Formation (SPL-RAF) mechanism described interactions with O2•−. The activity toward O2•− was A2–OH (1.26 × 106 M−1s−1) > A3–OH (7.71 × 105 M−1s−1) > A1–OH (4.22 × 105 M−1s−1). Molecular docking and dynamics studies tested inhibitory capability against enzymes producing reactive species: Lipoxygenase (LOX), Myeloperoxidase (MPO), NAD(P)H oxidase (NOX), and Xanthine Oxidase (XOD). Affinity to enzymes decreased in the order: XOD > LOX > NOX > MPO. [ABSTRACT FROM AUTHOR]

Ru(II)‐arene compounds are being investigated as anticancer agents due to the biocompatibility of ruthenium and their structural diversity. Two newly synthesized Ru(II) complexes, [RuCl(η6‐p‐cymene)(3‐DNPH)] (chlorido(η6‐p‐cymene)(3‐nitrophenylhydrazine‐k2N,N′)ruthenium(II)) (1) and [RuCl(η6‐p‐cymene)(3‐CNPH)] (chlorido(3‐chlorophenylhydrazine‐k2N,N′)(η6‐p‐cymene)ruthenium(II)) (2), are experimentally (IR, NMR) and theoretically (B3LYP/6‐31+G(d,p)(H,C,N,Cl)/LanL2DZ(Ru)) characterized. Experimental and theoretical values of 1H and 13C chemical shifts and position of the most intense vibrational bands showed high correlation coefficients and low mean absolute errors, proving the predicted structure and applicability of the selected level of theory. Cell viability studies performed on MDA‐MB‐468, BT‐474, and PC3 cells using MTT and CV assay indicated the activity of the second complex similar to the activity of cisplatin towards BT‐474 breast cancer cells. The spectrofluorimetric measurements of Bovine Serum Albumin showed the binding process's spontaneity of complexes and protein, with a binding energy of around −30 kJ mol−1. Detailed molecular docking analysis allowed the elucidation of the binding mechanism through specific intermolecular interactions. Both compounds showed a higher affinity towards BSA than naproxen and cisplatin. Molecular docking simulations proved the spontaneity of the complexes binding to DNA. Based on these promising results, further biological examinations of these compounds are advised. [ABSTRACT FROM AUTHOR]

The (pentamethylcyclopentadienyl)chloridoiridium(III) complex bearing a κP,κS-bonded Ph2PCH2CH2SPh ligand ([Ir(η5-C5Me5)Cl(Ph2P(CH2)2SPh-κP,κS)]PF6, (1)] was synthesized and characterized. Multinuclear (1H, 13C and 31P) NMR spectroscopy was employed for the determination of the structure. Moreover, SC-XRD confirmed the proposed structure belongs to the "piano stool" type. The Hirshfeld surface analysis outlined the most important intermolecular interactions in the structure. The crystallographic structure was optimized at the B3LYP-D3BJ/6-311++G(d,p)(H,C,P,S,Cl)/LanL2DZ(Ir) level of theory. The applicability of this level was verified through a comparison of experimental and theoretical bond lengths and angles, and 1H and 13C NMR chemical shifts. The Natural Bond Orbital theory was used to identify and quantify the intramolecular stabilization interactions, especially those between donor atoms and Ir(III) ions. Complex 1 was tested on antitumor activity against five human tumor cell lines: MCF-7 breast adenocarcinoma, SW480 colon adenocarcinoma, 518A2 melanoma, 8505C human thyroid carcinoma and A253 submandibular carcinoma. Complex 1 showed superior antitumor activity against cisplatin-resistant MCF-7, SW480 and 8505C cell lines. The mechanism of tumoricidal action on 8505C cells indicates the involvement of caspase-induced apoptosis, accompanied by a considerable reduction in ROS/RNS and proliferation potential of treated cells. [ABSTRACT FROM AUTHOR]

Ruthenium complexes have gained significant attention due to the ruthenium similarity to iron, lower toxicity, and higher anticancer effectiveness than other compounds. In this contribution, five new isonicotinate-polyethylene glycol ester ligands were synthesised and characterised by NMR and IR spectroscopies. The corresponding Ru(II) complexes were also obtained, and their structure was investigated by traditional methods. The optimisation of structures was performed at B3LYP/6-31+G(d,p) level of theory for H, C, N and O atoms and B3LYP/LanL2DZ for Ru. The intramolecular stabilisation interactions were assessed through the natural bond orbital approach. The NMR chemical shifts were predicted by the gauge independent atomic orbital method and compared to the experimental values. High correlation coefficients and low mean absolute errors between these data sets proved that the predicted structures described well the experimental ones. The theoretical and experimental IR spectra were also compared, and differences in the most notable bands were described. One of the ligands (L5) and complexes (5) showed fluorescent properties due to methylisatoic moiety. The electronic spectra of this compound were modelled by the time dependent-density functional theory method. The difference of 11 nm between the experimental and the theoretical wavelength was explained by the interactions between the solvent and the solute. Further biological and theoretical studies are advised for this series of compounds. [ABSTRACT FROM AUTHOR]