Intrinsic Binding Constant Research Articles

Synthesis, spectroscopic characterization, DNA binding and DFT/PCM calculations of new Hydrogen-bonded charge transfer complex between 4-dimethylaminopyridine and Chloranilic acid

A charge transfer hydrogen bonded complex between the electron donor 4-dimethylaminopyridine (4-DMAP) and the electron acceptor Chloranilic acid (CLA) has been synthesized. The complex was studied experimentally and theoretically. A chemical reaction developed due to strong H-bonding, followed by proton transfer from the CLA to the 4-DMAP in acetonitrile medium (ACN). The straight line approach was employed to verify the 1:1 M ratio of the synthesised CT complex. The Benesi-Hildebrand equation was employed to compute the association constant (KCT), molar absorptivity (εCT), and other physical parameters. The synthesized complex was characterized spectroscopically. The presence of proton and charge transfers in the resultant complex was supported by 1H NMR, FT-IR and SEM-EDX investigations. The complex DNA binding ability of complex was investigated using electron absorption spectroscopy to reveal that the CT complex binding mechanism is intercalative and the intrinsic binding constant (Kb) value is 6.7 × 104 M−1. Theoretical calculations using DFT at the basis set CAM-B3LYP/6–31 G (d, p) were used to validate the experimental outcomes. The Mullikan atomic charges, geometrical parameters, and molecular electrostatic potential maps (MEPs) were computed and interpreted in conformity with the experimental results. In addition to e-transfer, the presence of an H-bond influences complex stability. There is good agreement between experimental results and DFT calculations.

The Charge Transfer Complex between 2, 3-diamino-5-bromopyridine and Chloranilic acid: Preparation, Spectroscopic Characterization, DNA binding, and DFT/PCM analysis

A charge transfer hydrogen bonded complex was prepared and experimentally explored in an acetonitrile (ACN) medium between the proton acceptor (electron donor) 2, 3-Diamino-5-bromopyridine and the proton donor (electron acceptor) chloranilic acid. The stoichiometry of the charge transfer complex is 1:1. The Benesi-Hildebrand equation is used to calculate the molar absorptivity (εCT), association constant (KCT) and other spectroscopic physical characteristics. The solid compound was synthesized and studied using several spectroscopic methods. The presence of charge and proton transfers in the resultant complex was supported by 1H NMR, FT-IR and SEM-EDX investigations. The complex DNA binding ability was investigated using electron absorption spectroscopy, and the CT complex binding mechanism is intercalative. The intrinsic binding constant (Kb) value is 5.2 × 106M−1. The good binding affinity of the CT complex makes it potentially suitable for usage as a pharmaceutical in the future. Molecular docking calculations have been performed between CT complex and DNA (ID = 1BNA) to study the CT-DNA interaction theoretically. To corroborate the experimental findings, calculations based on DFT were carried out in the gas and PCM analysis where the existence of charge and hydrogen transfers. Finally, good agreement between experimental and theoretical computations was observed confirming that the basis set used is appropriate for the system under examination.

Synthesis, structural characterization and DNA binding properties of phthalazinylhydrazone-furan and triazolophthalazine-ferrocene compounds

A phthalazinylhydrazone (2) and two triazolophthalazines (3 and 4) derived from hydralazine were prepared and their structures were characterized by FTIR, 1H/13C NMR and elemental analysis. Compound 3 was prepared by cyclisation of compound 2 in the presence of FeCl2 as catalyst while compound 4 formed in the reaction without a catalyst. The crystal structures of the compounds 2 and 4 were determined by single crystal X-ray diffractions. The crystal structures of the compounds are mainly stabilised by π-π stacking interactions. The phthalazinylhydrazone (2) and triazolophthalazines compounds (3 and 4) showed distinctive UV-Vis absorption properties in solution. The structurally characterized compounds were studied for their double-stranded fish sperm DNA (Fsds-DNA) binding affinities. The UV-Vis spectral data showed that all three compounds exhibited comparable binding properties to Fsds-DNA with intrinsic binding (Kb) constants 4.50 × 104-4.85 × 105 M−1 range. The UV-Vis absorption data along with the ethidium bromide displacement and viscosity studies suggest that all three compounds interact with Fsds-DNA via intercalation.

Computational, Experimental and Pharmacological Studies of Cu(II), Co(II) and Ni(II) Metal Complexes containing Azo Schiff base Ligand

The metal complexes containing Cu(II), Co(II) and Ni(II) metal ions were synthesised in the molar ratio of 1:2 [M:L] and azo Schiff base ligand as a primary ligand. The synthesized metal complexes were confirmed by the different analytical and spectroscopic techniques like UV-Visible, FT-IR, NMR, LC-MS and P-XRD techniques. The binding interaction of synthesized metal chelates with CT-DNA has been investigated by absorption spectra, viscosity measurements and thermal denaturation techniques. The mode of binding of the metal complexes with calf-thymus DNA has been explored. The metal complexes [Cu(II), Co(II) and Ni(II)] intercalated between the base pairs of the CT-DNA tightly with intrinsic binding constant (Kb) in Tris - HCl buffer containing 50 mMNaCl buffer. The DNA cleavage activities of the complexes were clearly assayed by using pUC-18 DNA which was monitored by the gel electrophoresis method. The antibacterial activity was carried out by a well-diffusion method against gram-positive bacteria S. aureus and gram-negative bacteria Shigella. Amylase inhibitory activity of pooled fractions was carried out according to the standard method with minor modification (antidiabetic activity). The in silico molecular docking was achieved with the DNA binding receptor PDB ID: 1E3Y taken from RCSB Protein Data Bank (www.rcsb.org/pdb). The receptor structre was prepared before use in docking study using protein preparation module of HEX 8.2 modelling package.

‘On and Off’ intercalative binding behaviour of double chain surfactant cobalt(III) complex containing 2, 2′-bipyridyl ligand in β-Cyclodextrin: A detail approach on Host-guest inclusion of surfactant cobalt(III) complex and CT-DNA binding in micro-heterogeneous medium

The binding interaction of surfactant cobalt(III) complex, cis-[Co(bpy)2(HA)2](ClO4)3, in which bpy is 2,2-bipyridine and HA is hexadecylamine or cetylamnine with DNA was through intercalative mode via the long aliphatic chains present in the ligands. The binding was investigated by various techniques, electronic absorption, fluorescence spectroscopy, circular dichroism (CD), cyclic voltametry (CV) and viscosimetry measurements. The spectroscopic studies together with cyclic voltammetry and viscosity experiments support that the surfactant cobalt(III) complex binds to calf thymus DNA by intercalation through the aliphatic chain present in the complex into the base pairs of DNA. The presence of bipyridine ligand with larger π-frame work may also enhance intercalation. UV–vis., spectrum showed 4 nm bathochromic shift of the absorption band at 352 nm along with significant hypochromicity for the absorption band of the complex. The intrinsic binding constants(at below and above CMC are Kb = 2.41 × 105M−1, Kb = 3.12 × 106M−1 respectively) is more in keeping with intercalators and suggests this binding mode. The viscosity measurements showed that the surfactant cobalt(III) complex-DNA interaction can be hydrophobic and confirm intercalation. Moreover, the complex induced detectable changes in the CD spectrum of CT-DNA. Competitive binding study with ethidium bromide (EB) shows that the surfactant complex exhibits the ability to displace the DNA-bound EB indicating that the complex binds to DNA in strong competition with EB for the intercalative binding site. Also, CV results confirm this mode because, with increasing the CT-DNA concentration, shift to higher potential was observed. Besides the effect of binding of surfactant cobalt(III) complex to DNA in presence of β-cyclodextrin has also studied. This binding of the surfactant cobalt(III) complex in presence of β-cyclodextrin medium has been prevented (at below and above CMC are Kb = 5.45 × 104M−1, Kb = 6.92 × 105M−1 respectively) due to the incorporation of the aliphatic chains into the cavity of β-cyclodextrin. In presence of β-cyclodextrin the binding occur through surface and (or) groove binding can be attributed to the inclusion of the long aliphatic chain that is present in one of the ligands into cyclodextrin.

DNA interaction, cytotoxic and phototoxic properties of new water‐soluble zinc (II) phthalocyanines

In this paper, we have synthesized water‐soluble peripherally tetra and octa‐({6‐[3‐(dimethylamino)phenoxy]hexyl}oxy) groups substituted zinc (II) phthalocyanines (DM‐C6‐ZnQ and o‐DM‐C6‐ZnQ). Also, we have investigated ct‐DNA binding, supercoiled plasmid DNA cleavage properties of DM‐C6‐ZnQ and o‐DM‐C6‐ZnQ by using spectrophotometric and electrophoretic methods. On the other hand, cytotoxic and phototoxic effects of DM‐C6‐ZnQ and o‐DM‐C6‐ZnQ were examined using (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay on human lung adenocarcinoma (A549) cell lines. In UV–Vis absorption studies, hypochromism was observed about 18% for DM‐C6‐ZnQ and 57% for o‐DM‐C6‐ZnQ on addition of increasing concentrations of ct‐DNA. The intrinsic binding constant (Kb) values of DM‐C6‐ZnQ and o‐DM‐C6‐ZnQ were 3.82 (±0.14) × 104 M−1 and 2.34 (±0.05) × 105 M−1, respectively. The supercoiled plasmid DNA cleavage studies showed that DM‐C6‐ZnQ and o‐DM‐C6‐ZnQ had no DNA damage actions in the dark. On the other hand, they caused DNA damage depending on the light dose. In the MTT assay, the compounds had low cytotoxic properties on A549 cell lines, but they showed significant phototoxic actions. These results reveal that the compounds interact with DNA and have phototoxic properties; it has been determined that they have the potential to be photosensitizing agents for photodynamic therapy.

DNA interaction, molecular dynamics simulation, molecular docking, biological, in vivo anti‐inflammatory and thermal studies of o‐hydroxyacetophenone and 2‐fluoroaniline Schiff base complexes

Series of transition metal complexes [Fe (HL)2Cl(H2O)](1), [Co (HL)2](2), [Ni (HL)2](3) and [Cu (HL)2](4) were derived on condensation of Schiff base ligand o‐hydroxyacetophenone with 2‐fluoroaniline in 1:1 ratio (HL) and characterized by spectral and analytical techniques. Based on the studies, complex 1 was found to be octahedral and complexes (2), (3) and (4) square planar. Coats–Redfern calculations suggest that all the complexes are non‐spontaneous and thermally stable. DNA binding studies revealed intercalation binding mode, while intrinsic binding constant (Kb) and Stern–Volmer quenching constant (Ksq) support high binding abilities. The nuclease activity using CT‐DNA was studied by gel electrophoresis. Docking studies were deduced using Accelry's Discovery Studio 2.1 program to understand binding affinities. The MD simulation, carried in order to analyse the stability of ligand and human topoisomerase I (PDB ID: 1T8I) complex for 100 ns using the Desmond 2020.1 from Schrödinger, LLC, revealed stable conformation of the ligand. In vivo, carrageenan induced inflammation studies in paw volume were carried out in rats, and results showed a higher rate of oedema inhibition for complex 4. Cytotoxicity and antimicrobial assay reveal that complex 4 exhibited higher cytotoxic and antimicrobial activity over other complexes and the ligand.

Synthesis and characterization of violurate-based Mn(II) and Cu(II) complexes nano-crystallites as DNA-binders and therapeutics agents against SARS-CoV-2 virus

Synthesis and structural characterization of nano crystallites of bis-violurate-based manganese(II) and copper(II) chelates is the subject of the present study. Analytical data and mass spectra as well as thermal analysis determined the molecular formulas of the present metal chelates. Spectroscopic and magnetic measurements assigned the structural formula of the present violurate metal complexes. The spectroscopic and magnetic investigations along with structural analysis results indicated the square planar geometry of both the Mn(II) and Cu(II) complexes. The structural analysis of the synthesized metal complexes was achieved by processing the PXRD data using specialized software Expo 2014. Spectrophotometeric and viscosity measurements showed that violuric acid and its Mn(II) and Cu(II) complexes successfully bind to DNA with intrinsic binding constants Kb from 38.2 × 105 to 26.4 × 106 M−1. The antiviral activity study displayed that the inhibitory concentrations (IC50) of SARS-CoV-2 by violuric acid and its Mn(II) and Cu(II) complexes are 84.01, 39.58 and 44.86 μM respectively. Molecular docking calculations were performed on the SARS-CoV-2 virus protein and the computed binding energy values are −0.8, −3.860 −5.187 and −4.790, kcal/mol for the native ligand, violuric acid and its Mn(II) and Cu(II) complexes respectively. Insights into the relationship between structures of the current compounds and their degree of reactivity are discussed.

Intrinsic affinity of protein – ligand binding by differential scanning calorimetry

Differential scanning calorimetry (DSC) determines the enthalpy change upon protein unfolding and the melting temperature of the protein. Performing DSC of a protein in the presence of increasing concentrations of specifically-binding ligand yields a series of curves that can be fit to obtain the protein–ligand dissociation constant as done in the fluorescence-based thermal shift assay (FTSA, ThermoFluor, DSF). The enthalpy of unfolding, as directly determined by DSC, helps improving the precision of the fit. If the ligand binding is linked to protonation reactions, the intrinsic binding constant can be determined by performing the affinity determination at a series of pH values. Here, the intrinsic, pH-independent, affinity of acetazolamide binding to carbonic anhydrase (CA) II was determined. A series of high-affinity ligands binding to CAIX, an anticancer drug target, and CAII showed recognition and selectivity for the anticancer isozyme. Performing the DSC experiment in buffers of highly different enthalpies of protonation enabled to observe the ligand unbinding-linked protonation reactions and estimate the intrinsic enthalpy of binding. The heat capacity of combined unfolding and unbinding was determined by varying the ligand concentrations. Taken together, these parameters provided a detailed thermodynamic picture of the linked ligand binding and protein unfolding process.

Interaction of organoruthenium(II)-polypyridyl complexes with DNA and BSA.

The interaction of four arene ruthenium complexes [(η6-p-cymene)Ru(Me2dppz)Cl]PF6 (1) with Me2dppz = 11,12-dimethyldipyrido[3,2-a:2',3'-c]phenazine, [(η6-p-cymene)Ru(aip)Cl]PF6 (2) with aip = 2-(9-anthryl)-1H-imidazo[4,5-f][1,10] phenanthroline), ([(ƞ6-toluene)Ru(ppf)Cl]PF6) (3) and ([(ƞ6-p-cymene)Ru(ppf)Cl]PF6) (4) with ppf = pyrido[2',3':5,6] pyrazino[2,3-f][1,10]phenanthroline with calf thymus DNA were investigated. All of four complexes exhibit DNA-binding activity. UV-Vis spectroscopic studies revealed the intrinsic binding constants of the order 104M-1 of magnitude, indicating non-intercalative mode. Fluorescence quenching analysis showed that all complexes interfere with intercalator ethidium bromide and minor groove binder Hoechst 33258 by a singular non-intercalative mode with extent that differs by two orders of magnitude. Gel electrophoresis results on DNA cleavage assay demonstrated that all complexes produced conformational changes of supercoiled circular plasmid pUC19 in concentration dependent way. The results of fluorescence titration bovine serum albumin by 1, 2, 3 and 4 showed that all complexes significantly quench tryptophan residues fluorescence through a static quenching mechanism. The antimicrobial activity against both Gram-positive and Gram-negative bacteria analyzed. Complex 1 was most active, even on Escherichia coli was more active than positive control compound.

Mixed Ligand Mononuclear Copper(II) Complex as a Promising Anticancer Agent: Interaction Studies with DNA/HSA, Molecular Docking, and In Vitro Cytotoxicity Studies.

The isolated copper(II) complex [CuL(o-phen)]·H2O (1) [H2L = o-HO-C6H4C(H)=N-C6H4-SH-o, o-phen = 1,10-phenanthroline] was structurally characterized using single-crystal X-ray crystallography. 1 in CH3CN at liquid nitrogen temperature displayed a characteristic monomeric X-band electron paramagnetic resonance spectrum having a tetragonal character with g∥ = 2.1479 and g⊥ = 2.0691 and A∥ ≈ 18.0 mT and A⊥ ≤ 3.9 mT, respectively. 1 showed a strong binding affinity toward calf thymus DNA as reflected from its intrinsic binding constant (Kb = 7.88 × 105 M–1), and its competitive displacement of ethidium bromide suggested an intercalative DNA-binding mode (Kapp = 1.32 × 106 M–1). This was confirmed from the viscosity study that showed an increase in the viscosity of DNA with an increasing concentration of 1. Complex 1 is highly efficient in promoting oxidative and hydrolytic DNA cleavage (kobs = 1.987 h–1). 1 showed a strong binding affinity with the carrier protein human serum albumin (HSA) (Ka = 5.22 × 105 M–1). A high bimolecular quenching constant kq = 2.29 × 1013 M–1s–1 indicated a static quenching mechanism involved in the fluorescence quenching of HSA by 1. Fluorescence resonance energy transfer theory suggested that the distance (r = 3.52 nm) between 1 and HSA is very close. Molecular docking studies suggested that 1 primarily binds to HSA in subdomain IIA. A protein–ligand interaction profiler was used to visualize hydrophobic, hydrogen bonds, and π–cation interactions between HSA and 1. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay using HeLa and MDA-MB-231 cells showed a significant in vitro anticancer activity of 1 (IC50 2.63 and 2.68 μM, respectively). Nuclear staining assays suggested apoptotic cell death in HeLa cells treated with 1. The effect of 1 on the cytoskeletal actin filaments visualized using phalloidin staining showed extensive destruction of actin filaments. Flow cytometric analysis indicated that 1 inhibits the growth of HeLa cells through cell cycle arrest in the S phase. Western blot analysis showed upregulation in the expression of apoptotic marker proteins caspase 3, p53, and Bax. These results collectively indicate that 1 induces apoptosis by promoting DNA damage and has a high potential to act as an anticancer agent.

Classical Intermolecular Hydrogen Bonding Motifs of Heterocyclic rac-2-Amino-3-carbonitrile Derivatives: Linking Hirshfeld Surface Analysis, CT-DNA Binding Affinity, and Molecular Docking

Four 2-amino-4-(aryl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (Series I) and three 2-amino-1-phenyl-7,7-dimethyl-5-oxo-4-(aryl)-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (Series II) derivatives were formed via multicomponent microwave reactions as racemic mixtures. The solid-state IR spectra revealed bands in the region between 3190 and 3414 cm–1 attributed to the amino functional group’s asymmetric, symmetric, and bending overtone vibration modes. Furthermore, the IR spectra of some of the compounds in each series were similar and this served as an indication of similar structural features in the solid state. This was confirmed via single-crystal X-ray diffraction. A detailed survey of the related 2-amino-3-carbonitrile derivatives in the Cambridge Structural Database revealed 12 classical intermolecular hydrogen-bonding motifs involving the amino functional group. The vast variation in the hydrogen bonding motifs was found to be caused by the type of group bonded to the 4H-pyran (in Series I) or dihydropyridine (in Series II) moiety. In this work, an unprecedented hydrogen bonding motif comprising a non-classical hydrogen bond acceptor was found in one instance. For both Series I and II, the N–H···N and N–H···O hydrogen bonds were investigated using noncovalent interaction (NCI) plots and molecular pairwise energy calculations. The contributions of reciprocal N···H and O···H contacts (attributed to N–H···N and N–H···O, respectively) toward the Hirshfeld surface range between 9.9 and 15.3% in Series I and between 10.8 and 15.0% in Series II. In addition, the compounds showed moderate to good binding affinity to calf thymus DNA (CT-DNA) with intrinsic binding constants (Kb) between 8.00 × 104 and 5.00 × 105 M–1 for Series I compounds and between 6.60 × 104 and 1.45 × 105 M–1 for Series II. A relationship was established between the reciprocal N···H to O···H contributions ratio from the Hirshfeld surface analysis and Kb. Molecular docking studies of each compound’s respective enantiomers into DNA were done using canonical–DNA dodecamer (B-DNA) as a model for CT-DNA. The compounds were found to interact with DNA via a minor groove-binding mode. The S-enantiomer for most of the compounds bound favorably compared to their respective R-enantiomers. The ratio of calculated ΔG for the DNA binding of the R-enantiomer to that of the S-enantiomer (ΔGR/ΔGS) follows the same positive trend as the experimental Kb value for each compound in Series I while a negative trend was observed for Series II. Finally, a relationship between the Hirshfeld surface analysis and calculated ΔG values was also established in this work.

Synthesis, spectroscopic, anti-bacterial activity, molecular docking, ADMET, toxicity and DNA binding studies of divalent metal complexes of pyrazole-3-one azo ligand

Treatment equivalent molar of pyrazole-3-one azo (HPyoz) ligand with divalent metal ions {Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II)} afforded complexes of the chemical formula [MCl2(H2O)2(HPyoz)] {Co(II), Ni(II), and Cu(II)} or [MCl2(HPyoz)] {Zn(II), Cd(II) and Hg(II)}. The prepared complexes were characterized using IR, 1H, 13C NMR, Uv-visible spectra, xrd, SEM, conductance, and magnetic measurements. The results refer to that the HPyoz ligand behaves as bidentate via the nitrogen of azo group and oxygen of carbonyl group to afforded an octahedral complexes around transition metal ion {Co(II), Ni(II), and Cu(II)} or tetrahedral geometry around 12B group ions {Zn(II), Cd(II) and Hg(II)}. The results obtained from xrd and SEM images unequivocally declared the nano-sized of the prepared complexes. The lately studied compounds were examined for anti-bacterial activities towards four pathogenic species of bacteria. Molecular docking had been done based on screening against different targets, that show the good binding affinity of tested compounds with nucleoside diphosphate kinase (target site PDB ID: 3Q89), it's an important enzyme that generates nucleoside triphosphates (NTPs) or their deoxy derivatives by terminal phosphor-transfer from an NTP such as ATP or GTP to any nucleoside diphosphate or its deoxy derivative. As NTPs, particularly GTP, are important for cellular macromolecular synthesis and signaling mechanisms, Ndk plays an important role in bacterial growth, signal transduction and pathogenicity. In addition, The DNA binding properties of prepared complexes were evaluated. The intrinsic binding constant is calculated as 6.79 × 105, 4.72 × 105, 1.89 × 105 and 4.12 × 105M − 1 for the Ni-complex, Co-complex, Cu-complex and Zn-complex, and these results establish good binding characteristics of the prepared complexes with DNA

Synthesis, characterization, biological and docking studies of ZrO(II), VO(II) and Zn(II) complexes of a halogenated tetra-dentate Schiff base

The new Schiff base ligand 2,2′-{(4-chloro-1,2-phenylene)bis(nitrilo(E)methylylidene)}bis(4-bromophenol) (H 2 L) and its VO(II), Zn(II) and ZrO(II) metal chelates have been synthesized and characterized by spectral, powder x-ray diffraction (PXRD), molar conductance, magnetic measurements, thermal and elemental analyses. The molecular geometry of the prepared compounds has been confirmed by applying the theoretical density functional theory calculations (DFT). The analytical data showed that the parent azomethine H 2 L ligand binds to the VO(II), Zn(II) and ZrO(II) ions through both of the two azomethine-N and two phenolic-O groups and adopts distorted octahedral geometry for ZnL(H 2 O) 2 chelate while square pyramidal geometries for VOL and ZrOL chelates. The antioxidant activity of the compounds was also evaluated by using 1,1‐diphenyl‐2‐picrylhydrazyl (DDPH) reduction method and compared with the positive control ascorbic acid. Carcinoma cells such as breast (MCF-7), liver (Hep-G2), colon (HCT-116) carcinoma cell lines and human embryonic kidney 293 cells (HEK-293) were used for in vitro cell proliferation to investigate the anticancer potency of the prepared compounds. The results showed that, the tumor growth is inhibited and dose-dependent according to the following order: VOL > ZrOL > ZnL(H 2 O) 2 > H 2 L. The titled compounds have been also tested for their antimicrobial activity against certain pathogenic bacteria and fungi. The results showed that the H 2 L ligand and its complexes has enhanced antibacterial and antifungal activities. The CT-DNA binding experiments of azomethine chelates showed that, the binding modes are intercalative, and the determined intrinsic binding constants (K b ) for the VOL, ZrOL, ZnL(H 2 O) 2 complexes, are in the range 6.1–7.8 × 10 5 mol −1 dm −3 . The docking calculations were performed to probe the nature of binding affinity of the synthesized compounds with human DNA (PDB:1bna). The compounds may be applicable orally in an accurate manner, according to their in-silico intake, delivery, metabolic processes, digestion, and toxic effects (ADME) data.

Theoretical Investigation by DFT and Molecular Docking of Synthesized Oxidovanadium(IV)-Based Imidazole Drug Complexes as Promising Anticancer Agents.

Vanadium compounds have been set in various fields as anticancer, anti-diabetic, anti-parasitic, anti-viral, and anti-bacterial agents. This study reports the synthesis and structural characterization of oxidovanadium(IV)-based imidazole drug complexes by the elemental analyzer, molar conductance, magnetic moment, spectroscopic techniques, as well as thermal analysis. The obtained geometries were studied theoretically using density functional theory (DFT) under the B3LYP level. The DNA-binding nature of the ligands and their synthesized complexes has been studied by the electronic absorption titrations method. The biological studies were carried with in-vivo assays and the molecular docking method. The EPR spectra asserted the geometry around the vanadium center to be a square pyramid for metal complexes. The geometries have been confirmed using DFT under the B3LYP level. Moreover, the quantum parameters proposed promising bioactivity of the oxidovanadium(IV) complexes. The results of the DNA-binding revealed that the investigated complexes bind to DNA via non-covalent mode, and the intrinsic binding constant (Kb) value for the [VO(SO4)(MNZ)2] H2O complex was promising, which was 2.0 × 106 M−1. Additionally, the cytotoxic activity of the synthesized complexes exhibited good inhibition toward both hepatocellular carcinoma (HepG-2) and human breast cancer (HCF-7) cell lines. The results of molecular docking displayed good correlations with experimental cytotoxicity findings. Therefore, these findings suggest that our synthesized complexes can be introduced as effective anticancer agents.

Synthesis, characterization and DNA binding properties of Schiff base derivatives and Ru(II) complexes

Schiff base ligands were synthesized by condensation of 5-amino-1,10-phenanthroline with 4-hydroxybenzaldehyde (L1) and decanal (L2). Ruthenium (II) metal complexes (L1-Ru(II), L2-Ru(II)) were prepared in good yield from the reaction of the ligands with the bis(2,2′-bipyridine)ruthenium(II) dichloride. Structures of synthesized compounds were characterized using elemental analyze, FTIR, UV-Visible, 1H NMR and mass spectra. The DNA-binding properties of the ligands and complexes with calf thymus DNA was investigated by spectroscopic, gel electrophoresis and viscosity measurement.The interaction of the ligands and ruthenium complexes with calf tymus DNA (CT-DNA) have been demonstrated using electronic absorption titration method. Based on the UV–Vis spectroscopy, binding constants of the synthesized compounds with CT-DNA calculated. From the results, it is observed that L1 and L1-Ru(II) bind to CT-DNA via groove binding and electrostatic mode and L2 and L2-Ru(II) bind to CT-DNA via intercalation. Kb values of L1 and L1-Ru(II) with CT-DNA were calculated as 5.2 × 105 M−1 and 4.8 × 106 M−1, respectively. Absorption spectral study indicated that L2 and L2-Ru(II) have intrinsic binding constant (Kb) in the range of 3.8 × 105 -3.7 × 106 M−1. The results show that the complexes have more binding ability than the ligands.

Binding and Photocleavage Studies of Ru (II) Polypyridyl Complexes with DNA: An In Silico and Antibacterial activity

The global crisis of bacterial infections, search for an effective antibacterial is of utmost clinical significance. Experimental and computational approaches used to study the DNA binding of [Ru(A)2L] (ClO4)2.2H2O, where A=ancillary ligand; phen=1, 10 Phenanthroline (1), dmp=4,4’-dimethyl-1,10 -orthophenanthroline (2), bpy = bipyridyl (3) & dmb=4, 4’-dimethyl 2, 2’- bipyridine (4), Lis a novel intercalator ligand MPPIP=(2-(1-(2-methoxyphenyl)-1H-pyrazol-4-yl)-1H-imidazo [4,5-f][1,10]Phenanthroline) and their antibacterial activity. The synthesized complexes and their DNA affinity studies were executed by absorption, emission, and viscosity techniques to show binding via intercalation. The intrinsic binding constant, Kb indicates that the simple ancillary ligands (phen and bpy) are more robust binding. The 3D Conformational analysis shows slight distortion from octahedron geometry. The molecular descriptors calculated from the frontier molecular orbital energy gap, ΔE point that the complex of phen show higher binding with DNA. Further analysis of the molecular attributes show that the pyrazole ring of the intercalator Ligand is significant for DNA binding. Furthermore, the molecular docking studies of the Ru (II)-MPPIP complexes with DNA exhibit an inclination towards Guanine-rich sites by the Nitrogen of the pyrazole ring. Biological investigations establish that all the complexes were active against S. aureus and E. coli.

Metformin-Derived Water-Soluble Cobalt Complexes: Thermal, Spectroscopic, DNA Interaction, and Molecular Docking Studies.

Novel three water-soluble cobalt (II) complexes of type [Co(metf)(o-phen)2]Cl2 (1), [Co(metf)(opda)2]Cl2 (2), and [Co(metf)(2-2'bipy)2]Cl2 (3) (Metf, metformin; o-phen, ortho-phenanthroline; opda, ortho-phenylenediamine; 2,2'-bipy, 2,2'-bipyridine) were synthesized and characterized by various analytical and spectral techniques. Based on these studies, octahedral geometry is assigned to these complexes. The stability of the complexes has been calculated from quantum chemical parameters using HOMO-LUMO energies. Thermal degradation pattern of the compounds was studied and Coats-Redfern method is used to determine kinetic parameters for complexes 1, 2, and 3 from thermal studies. The DNA interaction of these complexes was investigated by absorption, emission, and viscosity studies. From the spectral data, it was concluded that the complexes bind to DNA through groove mode of binding. The intrinsic binding constants (Kb) from absorption spectroscopy were 2.49 × 104, 2.48 × 104, and 2.64 × 104M-1 for 1, 2, and 3, respectively, and Stern-Volmer quenching constants (Ksv) from emission spectroscopy were 0.21, 0.20, and 0.13, respectively. These complexes were screened for nuclease activity of pUC19 DNA, in the presence of H2O2. Discovery studio 2.1 software was used to evaluate binding affinity and interaction pattern of complexes with B-DNA receptor protein and the maximum dock score is seen for complex 2.

Quercetin - based rhodium(III) complex: Synthesis, characterization and diverse biological potentials

Quercetin – based rhodium(III) complex, [RhIIIL2ClH2O], L is quercetin, was synthesized via the direct interaction between the polyphenolic natural product (3,3′,4′,5,7-pentahydroxylflavone) and RhCl3 3H2O. Characterization of the pure isolated metal complex by analytical, electrolytic conductance, TGA and spectroscopic techniques demonstrated the stoichiometric ratio 1:2 metal to ligand. The final structure of [RhIIIL2ClH2O] was confirmed using PXRD–structural analysis by processing the XRD data of microcrystalline powder by the relevant computer program Expo 2014. The mimetic catalytic activity of superoxide dismutase (SOD) was studied and the obtained results showed that [RhIIIL2ClH2O] has mid activity compared to other SOD mimics. By analogy with the work of the original-SOD and its functional models, a mechanism for SOD-mimicking catalytic activity of the newly synthesized rhodium(III) complex has been proposed. The binding of the Rh(III) chelate to DNA was tested, and spectroscopic investigations indicated the successful binding of the metal complex to DNA by the groove/electrostatic binding pattern with intrinsic binding constants Kb of 2.76 × 106 M−1. In addition, the quercetin – based RhIII exhibits relatively higher DPPH scavenger power than the free quercetin. The in vitro data indicated the efficient anti-proliferative activities of the current rhodium(III) complex compared with cis-platin with increased safety on normal cells. In addition, our data revealed that the studied RhIII complex could prevent cancer cell replication with increasing the p53 levels, inhibit both Bcl2 and MMP9, then activating caspase 9, which then cleaves caspase 3, leading to apoptosis triggering. Apoptosis activation led to cell cycle arrest at the pre-G1 phase and decreased Hela cell proliferation, which appeared in the decreased G2/M phase. Ongoing biological assays indicate that the current Rh(III) complex is a promising anti-proliferative agent with minimal toxicity to normal cells.

Synthesis, Characterization, Crystal Structure, DNA and HSA Interactions, and Anticancer Activity of a Mononuclear Cu(II) Complex with a Schiff Base Ligand Containing a Thiadiazoline Moiety.

A mononuclear Cu(II) complex [Cu(HL)(o-phen)]·H2O (1) [H3L =, o-phen = 1,10-phenanthroline] was isolated from methanol, and its X-ray single-crystal structure was determined. Frozen glass X-band EPR of 1 in dimethylformamide (DMF) at LNT showed a spectrum that is characteristic of a monomeric tetragonal character with g∥ = 2.164, g⊥ = 2.087, A∥ = 19.08 mT, and A⊥ ≤ 4 mT. Electronic spectroscopic studies using calf thymus DNA (CT-DNA) showed strong binding affinity of 1 as reflected from its intrinsic binding constant (Kb) value of 2.85 × 105 M–1. Competitive behavior of 1 with ethidium bromide (EB) displayed intercalative binding of DNA (Kapp= 1.3 × 106 M–1). The compound displayed significant oxidative cleavage of pUC19 DNA. The interaction between HSA and complex 1 was examined by employing fluorescence and electronic absorption spectroscopic experiments. The secondary and tertiary structures of HSA were found to be altered as suggested by three-dimensional (3D) fluorescence experiments. The affinity of 1 to bind to HSA was found to be strong as indicated from its value of the binding constant (Ka = 2.89 × 105 M–1). Intrinsic fluorescence of the protein was found to be reduced through a mechanism of static quenching as suggested from the kq (2.01 × 1013 M–1 s–1) value, the bimolecular quenching constant. The Förster resonance energy transfer (FRET) process may also be accounted for such a high kq value. The r value (2.85 nm) calculated from FRET theory suggested that the distance between complex 1 (acceptor) and HSA (donor) is quite close. Complex 1 primarily bound to HSA in subdomain IIA as suggested by molecular docking studies. IC50 values (0.80 and 0.43 μM, respectively) obtained from the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with HeLa and MCF7 cells suggested remarkable in vitro anticancer activity of 1. Nuclear dual staining assays revealed that cell death occurred via apoptosis in HeLa cells and reactive oxygen species (ROS) accumulation caused apoptosis induction. On treatment with a 5 μM dose of 1 in HeLa cells, the cell population significantly increased in the G2/M phase, while it was decreased in G0/G1 and S phases as compared to the control, clearly indicating G2/M phase arrest.