Groove Binding Mode Research Articles

Co(II), Ni(II), and Cu(II) Ternary Complexes With 2,6‐Pyridinedicarboxylic Acid and 2,2′‐Bipyridyl: Synthesis, Characterization, DNA Binding, Photo‐Cleavage, and Antimicrobial Studies

ABSTRACTThe interaction of 2,6‐pyridinedicarboxylicacid (PDA) and 2,2′‐bipyridyl (Bipy) with Co(II), Ni(II), and Cu(II) ions produced new ternary complexes [M (PDA)(Bipy)(H2O)] (M = Co(II), Ni(II), and Cu(II)), which were studied by elemental, spectral (FT‐IR, Mass, UV–Vis), and thermal analysis, and their interaction with Ct‐DNA was thoroughly studied using various methods, including absorption spectroscopy, fluorescence spectroscopy, and viscosity measurements. Spectrophotometric titration and viscosity measurements indicated that all the complexes bind to DNA via the groove mode of binding. The salt‐dependent binding of ternary metal complexes to Ct‐DNA has been studied by a UV–Vis spectrophotometric titration experiment. Furthermore, photocleavage studies were used to examine how the metal complexes interacted with the pBR322 DNA, and the results proved that these compounds have obvious photo cleavage properties. The biological effects were studied by antibacterial activity.

Mechanistic Studies of Small Molecule Ligands Selective to RNA Single G Bulges.

Small-molecule RNA binders have emerged as an important pharmacological modality. A profound understanding of the ligand selectivity, binding mode, and influential factors governing ligand engagement with RNA targets is the foundation for rational ligand design. Here, we report a novel class of coumarin derivatives exhibiting selective binding affinity towards single G RNA bulges. Harnessing the computational power of all-atom Gaussian accelerated Molecular Dynamics (GaMD) simulations, we unveiled a rare minor groove binding mode of the ligand with a key interaction between the coumarin moiety and the G bulge. This predicted binding mode is consistent with results obtained from structure-activity-relationship (SAR) studies and transverse relaxation measurements by NMR spectroscopy. We further generated 444 molecular descriptors from 69 coumarin derivatives and identified key contributors to the binding events, such as charge state and planarity, by lasso (least absolute shrinkage and selection operator) regression. Strikingly, small structure perturbations on these key contributors, such as the addition of a methyl group that disrupts the planarity of the ligand resulted in > 100-fold reduction in the binding affinity. Our work deepened the understanding of RNA-small molecule interactions and integrated a new generalizable platform for the rational design of selective small-molecule RNA binders.

Effects of Ring Functionalization in Anthracene-Based Cyclophanes on the Binding Properties Toward Nucleotides and DNA.

Supramolecular recognition of nucleobases and short sequences is an emerging research field focusing on possible applications to treat many diseases. Controlling the affinity and selectivity of synthetic receptors to target desired nucleotides or short sequences is a highly challenging task. Herein, we elucidate the effect of substituents in the phenyl ring of the anthracene-benzene azacyclophane on the recognition of nucleoside triphosphates (NTPs) and double-stranded DNA. We show that introducing phenyl rings increases the affinity for NTPs 10-fold and implements groove and intercalation binding modes with double-stranded DNA. NMR studies and molecular modeling calculations support the ability of cyclophanes to encapsulate nucleobases as part of nucleotides.

Tyramine Derivatives as Versatile Pharmacophores With Potent Biological Properties: Sex Hormone-Binding Globulin Inhibition, Colon Cancer Antimigration, and Antimicrobial Activity.

Guided by the idea that the presence of a heterocyclic aromatic core and tyramine moiety, under the umbrella of a single molecular scaffold could bring interesting biological properties, herein we present synthesis, characterization, with two crystal structures reported, and biological evaluation of some tyramine derivates. Cytotoxic and antimigratory potential was addressed by using a colorectal cancer cell line as a model system. Although possessing no cytotoxic effects, two compounds have shown strong antimigratory potential in low doses, with no effect on healthy MRC-5 cells. Evaluation of their antimicrobial activities suggested prominent antimicrobial activity, where Compound 4 outperformed streptomycin against Escherichia coli and Proteus mirabilis. Hormone-dependent types of cancer, such as prostate, ovary, and breast, are highly dependent on human sex hormone-binding globulin (SHBG) blood levels. A molecular docking study has shown that 1 has high affinity to bind and therefore compete with natural steroids for the SHBG steroid-binding site. DNA-binding study have shown that 4 interacts with CT-DNA in a groove-binding mode. In silico ADME/T study revealed that all compounds have suitable physicochemical properties for oral bioavailability and druglikeness, while toxicity tests for 1, 4, and 6 suggested potential for mutagenicity (4, 6), hepatotoxicity (6), and skin sensation (1).

Designing of amiloride loaded citrate functionalized amorphous silica nanoparticles to investigate its genotoxic and cytotoxic potential

In the present work, silica-based nanocarrier for the anticancer drug, amiloride have been synthesized and characterized using various physicochemical techniques. The aim of this work emphasis on investigating the physicochemical properties and cytotoxic effects of citrate-functionalized amiloride loaded silica nanoparticles. Silica nanoparticles synthesis was carried out via condensation reaction, then coated by tris sodium citrate, followed by their functionalization using amiloride through EDC-NHS reaction. SEM and HR-XRD analysis indicated the formation of amorphous spherical silica nanoparticles. The existence of citrate coating was evident from FT-IR and TGA results, which were supported by DLS and zeta potential studies. The formation of amiloride conjugated citrate coated silica nanoparticles (SiNPs-Cit@Ami) was confirmed by the DLS, Zeta potential and UV-Visible spectroscopy. Size of SiNPs-Cit@Ami nanoparticles was found to be around 80nm using TEM. Additionally, these nanoparticles showed high loading efficiency and time-dependent release of amiloride. DNA binding studies were examined using UV–Visible, Fluorescence spectroscopic and Competitive fluorescence studies. The results indicate that SiNPs-Cit@Ami bind to Ct-DNA via minor groove binding mode. Furthermore, the cytotoxic effect of SiNPs-Cit@Ami on HepG2 cell lines was found to be higher than amiloride alone. Our findings suggest that SiNPs-Cit@Ami can be employed as a promising candidate for cancer mitigation.

Transition metal complexes of benzimidazole-based ligands: Synthesis, characterization, biological, and catecholase activities

Heterocyclic ligands 5a and 5b and their metal complexes (1–10) and (11–20) respectively, were synthesized and characterized by mass spectrometry, FT-IR, ESR, 1H, 13C NMR and UV–visible spectroscopy. In vitro antifungal activity of the heterocyclic analogs 5a, 5b and metal complexes (1–20) was evaluated against the fungal strains: Candida albicans, Candida glabrata, and Candida tropicalis., The results showed that Fe(III) 2 and Co(II) complex 13 display considerable antifungal activity with MIC values of 350, 375 and 435 μg/mL and 450, 455, and 455 μg/mL against C. albicans, C. glabrata, and C. tropicalis, respectively. Promising 5a, 5b, Fe(III) 2, and Co(II) complex 13 show groove binding mode with Ct-DNA, which has been confirmed by several techniques, including UV–visible, fluorescence spectroscopy, and cyclic voltammetry. PDB ID: 1BNA was used for the molecular docking investigation of the heterocyclic analogs 5a and 5b. The active Fe(III) complex 2 and Co(II) complex 13 are effectively catalyzed for the oxidation of catechol in acetonitrile to its corresponding quinone with turnover number 5.44 × 104 and 9.78 × 104 h−1, respectively with first order that follow Michaelis-Menten enzymatic kinetics. The pharmacokinetics properties of the all compounds showed good oral bioavailability. Antioxidant potential of ligands 5a, 5b, Fe(III) 2 and Co(II) complex 13 was further approximated through DPPH free radical and H2O2 with remarkable antioxidant activity.

A second life for the crystallographic structure of Berenil-dodecanucleotide complex: a computational revisitation thirty years after its publication

AbstractThis study revisits the pioneering work of Professor Neidle, and co-workers, on the crystal structure of complexes formed between groove binders and DNA sequences. The original research revealed a DNA-ligand complex consisting of a dodecanucleotide bound with Berenil [1,3-bis(4′-amidinophenyl)-triazene] an anti-trypanocidal drug. This article aims to delve deeper into the structural dynamics of this system, showcasing the role played by water molecules in stabilizing the interaction between the ligand and the DNA. With this work, we reevaluate the findings from the original crystallographic study by employing modern molecular dynamics techniques, including Supervised Molecular Dynamics (SuMD) for generating binding trajectories, Thermal Titration Molecular Dynamics for assessing unbinding events, and AquaMMapS to identify regions occupied by stationary water molecules. The study addresses a minor and a major groove binding mode and assesses their strength and specificity using TTMD simulations, generating unbinding trajectories. This comprehensive approach integrates the understanding of the interaction of this DNA-ligand complex, which originated with the valuable work of Professor Neidle, resulting in an in-depth insight into the pivotal role of water molecules with this DNA, a behavior detected and extendable even to other nucleic acid complexes.

Study on the electrochemical and spectroscopic characteristics of holmium ion and its interaction with DNA

Metal ion-DNA interactions play a crucial role in modulating the structure and function of genetic material in the natural environment. In this study, we report on the favorable electrochemical activity of holmium(III) (Ho3+) on a glassy carbon electrode (GCE) and its interaction with double-stranded DNA. The interaction between DNA and Ho3+ was investigated for the first time using cyclic voltammetry and differential pulse voltammetry. The electrochemical behavior of Ho3+ ions on a GCE exhibited a reversible electron transfer process, indicative of its redox activity. A linear correlation between the peak current and the square root of the scan rate was observed, suggesting a diffusion-controlled kinetic regime for the electrochemical process. Additionally, fluorescence and absorption spectroscopy were employed to confirm the binding of Ho3+ to DNA. Our findings demonstrate that, at pH 7.2, specific DNA bases and phosphate groups can interact with Ho3+ ions. Moreover, electrochemical measurements suggest that Ho3+ ions bind to DNA via a groove binding mode, with a calculated binding ratio of 1:1 between Ho3+ and DNA. Notably, under optimal conditions, an increase in the amount of DNA leads to a significant reduction in the current intensity of Ho3+ ions.

A Minor Groove Binder with Significant Cytotoxicity on Human Lung Cancer Cells: The Potential of Hesperetin Functionalised Silver Nanoparticles.

Natural drug functionalised silver (Ag) nanoparticles (NPs) have gained significant interest in pharmacology related applications due to their therapeutic efficiency. We have synthesised silver nanoparticle using hesperetin as a reducing and capping agent. This work aims to discuss the relevance of the hesperetin functionalised silver nanoparticles (H-AgNPs) in the field of nano-medicine. The article primarily investigates the anticancer activity of H-AgNPs and then their interactions with calf thymus DNA (ctDNA) through spectroscopic and thermodynamic techniques. The green synthesised H-AgNPs are stable, spherical in shape and size of 10 ± 3nm average diameter. The complex formation of H-AgNPs with ctDNA was established by UV-Visible absorption, fluorescent dye displacement assay, isothermal calorimetry and viscosity measurements. The binding constants obtained from these experiments were consistently in the order of 104 Mol-1. The melting temperature analysis and FTIR measurements confirmed that the structural alterations of ctDNA by the presence of H-AgNPs are minimal. All the thermodynamic variables and the endothermic binding nature were acquired from ITC experiments. All these experimental outcomes reveal the formation of H-AgNPs-ctDNA complex, and the results consistently verify the minor groove binding mode of H-AgNPs. The binding constant and limit of detection of 1.8μM found from the interaction studies imply the DNA detection efficiency of H-AgNPs. The cytotoxicity of H-AgNPs against A549 and L929 cell lines were determined by in vitro MTT cell viability assay and lactate dehydrogenase (LDH) assay. The cell viability and LDH enzyme release are confirmed that the H-AgNPs has high anticancer activity. Moreover, the calculated LD50 value for H-AgNPs against lung cancer cells is 118.49µl/ml, which is a low value comparing with the value for fibroblast cells (269.35µl/ml). In short, the results of in vitro cytotoxicity assays revealed that the synthesised nanoparticles can be considered in applications related to cancer treatments. Also, we have found that, H-AgNPs is a minor groove binder, and having high DNA detection efficiency.

DNA Interaction, Molecular Docking, Antimicrobial, Anticancer and Thermal Studies of Ternary Metal Complexes of N‐Methylbenzylamine and Ethylenediamine

ABSTRACTN‐Methylbenzylamine and ethylenediamine were utilized as primary and auxiliary ligands, respectively, alongside metal salts to synthesize ternary metal complexes: [FeCl3(Nmba)(en)], [CoCl2(Nmba)(en)(H2O)] and [CuCl2(Nmba)(en)(H2O)]. These complexes were thoroughly characterized using spectral and analytical techniques, revealing an octahedral geometry for all. Coats–Redfern calculations indicated their non‐spontaneous nature yet highlighted their thermal stability. DNA binding studies unveiled a groove binding mode for the complexes, with intrinsic binding constants (Kb) and Stern–Volmer quenching constant (Ksq) supporting their strong binding capabilities. Nuclease activity against pBR322 was assessed through gel electrophoresis. Additionally, docking studies using AutoDock 4.2 software provided insights into their binding affinities. In terms of biological activities, the Cu complex demonstrated superior cytotoxicity and antibacterial and antifungal properties compared to the other ternary metal complexes. This suggests its potential for further exploration in biomedical applications.

Inclusion complexes of novel formyl chromone Schiff bases with β-Cyclodextrin: Synthesis, characterization, DNA binding studies and in-vitro release study

The present study involved the synthesis of five novel Schiff bases (SB1-SB5) of formyl chromone and their inclusion complexes with β-cyclodextrin through kneading approach to enhance the solubility and stability of SBs. Characterization was conducted using FTIR, NMR, SEM, TEM, p-XRD, and Mass Spectrometry. UV fluorescence and pH stability studies confirmed the formation of the inclusion complex. Structural validation of complexes was conducted via molecular docking (PDB ID: 1BFN) and 50 ns MD simulation study. DFT studies were performed on SBs using B3LYP/6–31 + G(d,p) basis set. All SBs exhibited favorable ADME properties and high binding interactions were observed in molecular docking with ctDNA (PDB Id: 1BNA). Further, in-vitro UV absorption and fluorescence experiments demonstrated strong ctDNA interactions for all Schiff bases, with binding constants in the order of 105 M−1, indicating groove binding mode. Among the SBs, SB4 exhibited the highest affinity for DNA grooves, with a binding constant (Kb) of 1.7 × 106 M−1. However, the SB4/β-Cyd inclusion complex also interacted with DNA but with low binding constants compared to SB4. An in-vitro release study of SB4/β-Cyd, revealed 78.92 % dissolution of the inclusion complex, highlighting its potential for enhanced solubility and stability in biological systems.

Insights on the comparative affinity of ribonucleic acids with plant-based beta carboline alkaloid, harmine: Spectroscopic, calorimetric and computational evaluation

Small molecules as ligands target multifunctional ribonucleic acids (RNA) for therapeutic engagement. This study explores how the anticancer DNA intercalator harmine interacts various motifs of RNAs, including the single-stranded A-form poly (rA), the clover leaf tRNAphe, and the double-stranded A-form poly (rC)-poly (rG). Harmine showed the affinity to the polynucleotides in the order, poly (rA) > tRNAphe > poly (rC)·poly (rG). While no induced circular dichroism change was detected with poly (rC)poly (rG), significant structural alterations of poly (rA) followed by tRNAphe and occurrence of concurrent initiation of optical activity in the attached achiral molecule of alkaloid was reported. At 25 °C, the affinity further showed exothermic and entropy-driven binding. The interaction also highlighted heat capacity (ΔCop) and Gibbs energy contribution from the hydrophobic transfer (ΔGhyd) of binding with harmine. Molecular docking calculations indicated that harmine exhibits higher affinity for poly (rA) compared to tRNAphe and poly (rC)·poly (rG). Subsequent molecular dynamics simulations were conducted to investigate the binding mode and stability of harmine with poly(A), tRNAphe, and poly (rC)·poly (rG). The results revealed that harmine adopts a partial intercalative binding with poly (rA) and tRNAphe, characterized by pronounced stacking forces and stronger binding free energy observed with poly (rA), while a comparatively weaker binding free energy was observed with tRNAphe. In contrast, the stacking forces with poly (rC)·poly (rG) were comparatively less pronounced and adopts a groove binding mode. It was also supported by ferrocyanide quenching analysis. All these findings univocally provide detailed insight into the binding specificity of harmine, to single stranded poly (rA) over other RNA motifs, probably suggesting a self-structure formation in poly (rA) with harmine and its potential as a lead compound for RNA based drug targeting.

Donepezil-Squaric Acid Hybrid: Synthesis, Characterization and Investigation of Anticholinesterase Inhibitory, DNA Binding and Antioxidant Properties

A novel donepezil-squaric acid (DS) hybrid compound was designed, synthesized and biologically evaluated as multi-target-directed ligands against neurodegenerative disease by fusing a fragment of donepezil (D) and squaric acid (S). This study focuses on investigating the binding mechanism of double-stranded fish sperm DNA (Fsds-DNA) with DS and S. The interaction between DS and S with Fsds-DNA was explored using spectrophotometric and viscometric methods. Besides, DNA binding constants (Kb) were determined. The results reveal that DS binds to Fsds-DNA via the minor groove binding mode. The hybrid molecule demonstrates potent inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Furthermore, it exhibits significant antioxidant activity, surpassing the scavenging ability of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals compared to squaric acid alone. In conclusion, these results suggest that the hybrid molecule may serve as a potential multifunctional agent for the treatment of Alzheimer’s disease.

New bioactive titanium(IV) derivatives with their DFT, molecular docking, DNA/BSA interaction, antioxidant and in-vitro investigations

A set of four new metallacyclic complexes titanium(IV) associated with Schiff bases (SBs) (1a- 1d) obtained by the specific reactions of β-diketones such as acetylacetone (acacH) and benzyl acetone (bzacH) and aminophenol derivatives while treating Ti(OPri)4 and these SBs individually in 1:2 stoichiometry under 8 h reflux condition in anhydrous benzene to afford as reddish powder (2a-2d). These products have been purified in repeated washings of dry n-hexane afterwards, subjected to characterization by suitable spectroscopic techniques (NMR, IR, UV–Vis and HRMS). These hexacoordinated complexes appeared as distorted octahedral geometry from computational data studies. The synthesized titanium(IV) complexes were screened for their antioxidant abilities where 2c and 2d exhibited remarkable activity as IC50 values. The DNA & BSA binding properties of the complexes (2a-2d) have also been investigated through electronic absorption and molecular docking analysis. The obtained results indicated clearly that the complexes got bound with DNA via groove binding mode according to the intrinsic binding constant values (Kb = 1.5 × 104 M−1 to 7.5 × 105 M−1). Derivative 2c was examined in-vitro on a panel of cancerous cell line − breast cancer and human colon cell lines MCF-7 to reflect IC50 results as 53.92 μg/mL and HT-29 33.43 μg/mL, respectively.

Evaluation of the interaction between new holmium(III) complex and DNA: A comprehensive study

In this research, we conducted a comprehensive investigation into the interactions between the holmium(III)-curcumin complex ([Ho(Cur)2]+) and DNA. To elucidate these interactions, we employed various analytical techniques including cyclic voltammetry (CV), UV–Vis spectroscopy, Fourier transform infrared spectroscopy (FT-IR), fluorescence spectrophotometry, thermal gravimetric analysis (TGA), and molecular docking calculations. Our findings revealed compelling evidence of strong binding between [Ho(Cur)2]+ and DNA, as indicated by hypochromic effects in absorbance and fluorescence quenching. The binding affinity of [Ho(Cur)2]+ to DNA was substantiated by the evaluation of maximum absorption of the [Ho(Cur)2]+ spectra at different DNA concentrations. Furthermore, fluorescence resonance energy transfer experiments demonstrated that the distance between the donor (DNA) and acceptor ([Ho(Cur)2]+) was favorable for energy transfer. The combination of experimental data and molecular docking results suggested that non-covalent binding likely played a significant role in the binding of [Ho(Cur)2]+ to DNA. FT-IR spectra and molecular docking analyses provided further insights, indicating specific binding primarily between [Ho(Cur)2]+ and the base pairs of DNA. Electrochemical measurements indicated a groove binding mode between [Ho(Cur)2]+ and DNA, with a binding ratio of 1:1. Notably, our results indicated that increasing the amount of DNA resulted in a significant reduction in the current intensity of [Ho(Cur)2]+ under optimal conditions.

Mixed N‐heterocyclic carbene and benzyl‐, phenethyl‐, and biphenylamine coordinated Pd complexes: Anticancer activities and stereo‐electronic effects

A series of mixed N‐heterocylic carbene (NHC) palladium complexes bearing C^N bidentate ligands derived from benzylamine, phenethylamine, and biphenylamine were prepared and fully characterized by NMR spectroscopy, ESI‐MS spectrometry, and X‐ray diffraction analyses. The complexes were potent in inhibiting proliferation of HepG2 and Caco2 cancer cells, and a SAR (structure–activity relationship) study revealed C^N ligands with stronger electron donation and moderate steric hindrance are more cytotoxic. DNA binding study through UV–vis absorption titration indicated that such complexes bound stronger to CT‐DNA molecules with higher binding constants. Additional molecular docking of the best performer suggested a groove binding mode through hydrogen bonding and π‐π stacking interactions. The apoptosis induced by the two best performers of α,α‐dimethylbenzylamine and S‐α‐methylbenzylamine ligated complexes was further analyzed by morphology change, cell cycle distribution, ROS production, and mitochondrial membrane potential studies.

Higher-order G-quadruplex structures and porphyrin ligands: Towards a non-ambiguous relationship

Herein, we evaluated the interaction of the tetracationic porphyrin H2TCPPSpm4 with three distinct DNA G-quadruplex (G4) models, i.e., the tetramolecular G4 d(TGGGGT)4 (Q1), the 5′-5′ stacked G4-dimer [d(CGGAGGT)4]2 (Q2), and a mixture of 5′-5′ stacked G-wires [d(5′-CGGT-3′-3′-GGC-5′)4]n (Qn). The combined data obtained from UV–Vis, CD, fluorescence, PAGE, RLS, AFM, NMR, and HPLC-SEC experiments allowed us to shed light on the binding mode of H2TCPPSpm4 with the three G4 models differing for the type and the number of available G4 ending faces, the length of the G4 units, and the number of stacked G4 building blocks. Specifically, we found that H2TCPPSpm4 interacted with the shortest Q1 as an end-stacking ligand, whereas the groove binding mode was ascertained in the case of the Q2 and Qn G4 models. In the case of the interaction with Q1 and Qn, we found that H2TCPPSpm4 induces the formation of supramolecular aggregates at porphyrin/G4 ratios higher than 2:1, whereas no significant aggregation was observed for the interaction with Q2 up to the 5:1 ratio. These results unambiguously demonstrated the suitability of porphyrins for the development of specific G4 ligands or G4-targeting diagnostic probes, being H2TCPPSpm4 capable to distinguish between different G4s.

A disaggregation-driven BODPIY-based probe for ratiometric detection of G4 DNA

In conventional systems, fluorescent probes with planar structures usually experience the phenomenon of aggregation-induced quenching (ACQ) that limits their practical applications in bio-medical sensing. To confront such problem, an attractive way is to develop a disaggregation-induced emission (DIE) sensing strategy, where the quenched fluorescence is recovered via a disaggregation process. Currently most of the fluorescent probes designed based on DIE mechanism are signal off-on type with the fluorescent intensity changed at a single wavelength. On the other hand, ratiometric fluorescent probes have the advantage of having two distinct emission wavelengths, effectively avoiding environmental interference. The DIE probes with a ratiometric fluorescence response still poorly established. Herein, we report a BODIPY-based probe BODPA, where a 2,2′-dipicolylamine group was introduced to the meso-position of BODIPY core, for the selective ratiometric detection of G-quadruplex (G4) DNA. This probe in buffer solution formed aggregates with weak fluorescence at 508 nm. In the presence of G4 DNA, bright fluorescence was emitted at 518 nm through DIE mechanism. Taking advantage of the ratiometric manner, probe BODPA exhibited selectivity for G4 DNA over duplex DNA. The binding details between probe BODPA and G4 DNA were assessed by spectroscopic and molecular modeling methods, which suggested the ability of this probe could coordinate with G4 structure via end stacking and partial groove binding mode.

Co (II), Ni (II), and Cu (II) ternary complexes with 2,6‐pyridinedicarboxylic acid: Thermal decomposition, DNA interaction, and biological activity studies

Three novel ternary complexes [MII (PDA)(o‐phen)(H2O)] (MII = CoII, NiII, and CuII) were synthesized using 2,6‐pyridinedicarboxylicacid as a primary ligand and 1,10‐phenanthroline(o‐phen) as the auxiliary ligand and analyzed by FT‐IR, mass, UV–Vis, thermogravimetry analysis, and conductivity measurement data. Based on electronic spectral measurements, all three of the metal complexes were found to have octahedral stereochemistry. The way metal complexes interact with ct‐DNA was studied using various methods including absorption spectroscopy, fluorescence spectroscopy, and viscosity measurements. UV–Vis absorption technique has been used to explore the binding characteristics of M (II) complexes with ct‐DNA. The complexes bind to DNA via groove mode of binding, according to the spectral data. The salt‐dependent binding of ternary metal complexes to ct‐DNA has been studied by UV–Vis spectrophotometric titration experiment. Furthermore, gel electrophoresis is used to examine how the metal complexes interacted with the pBR322 DNA. The outcomes showed that these compounds can function as efficient DNA cleaving agents. Studies on the complexes' in vitro antibacterial activity demonstrated their importance and good antimicrobial activity at three distinct concentrations (50, 75, and 100 g/mL).

Theoretical, DNA/BSA Binding, Molecular Docking and In Vitro Cytotoxicity Studies of Homoleptic Metal(II) Complexes Derived from 2‐Formylpyridine‐Based Ligands

AbstractA new class of homoleptic metal(II) complexes of general formula [M(L1–4)2]2Cl in which L1=1‐([1,1′‐biphenyl]‐4‐yl)‐N‐(2‐((‐pyridin‐2‐ylmethylene)amino)ethyl)methanimine, L2=1‐([1,1′‐biphenyl]‐4‐yl)‐N‐(2‐((‐pyridin‐2‐ylmethylene)amino)phenyl)methanimine, L3=1‐([1,1′‐biphenyl]‐4‐yl)‐N‐(2‐((‐pyridin‐2‐ylmethylene)amino)‐4‐nitrophenyl)methanimine and L4=4‐(([1,1′‐biphenyl]‐4‐ylmethylene)amino)‐3‐((−pyridin‐2‐ylmethylene)amino)benzophenone, and M=Ni(II) (1–4), Cu(II) (5–8) and Zn(II) (9–12) have been synthesized and characterized. The IR spectra reveal the involvement of azomethine and 2‐formylpyridine ring nitrogen atoms in chelation. The UV‐Vis and EPR spectral studies envisage distorted octahedral geometry around metal(II) ion. All the complexes were stable for 72 h in biologically relevant solutions, and copper(II) complexes were reduced to Cu+ center in the presence of ascorbic acid solution. The binding studies of complexes with calf thymus DNA (CT‐DNA) indicate groove mode of binding, and the complexes 3, 7 and 11 containing the 4‐nitrophenyl substituent exhibit the highest binding affinity than the other complexes. Furthermore, the spectral studies also revealed the interaction of complexes with BSA through static mechanism. In vitro cytotoxicity activity of the complexes was screened against human lung adenocarcinoma (A549) and breast adenocarcinoma (MCF‐7) cancerous, and normal murine fibrosarcoma (L929) cell lines. The molecular docking studies of the homoleptic metal(II) complexes show hydrophobic, π–π, σ–π and hydrogen bonding interactions with EGFR/VEGFR2 kinase receptors.