Groove Binding Mode Research Articles

Chiral halogenated Schiff base compounds: green synthesis, anticancer activity and DNA-binding study

Eight enantiomerically pure halogenated Schiff base compounds were synthesized by reaction of halogenated salicylaldehydes with 3-Amino-1,2-propanediol (R or S) in water as green solvent at ambient temperature. All compounds were characterized by elemental analyses, NMR (1H and 13C), circular dichroism (CD) and FT-IR spectroscopy. FS-DNA binding studies of these compounds carried out by fluorescence quenching and UV–vis spectroscopy. The obtained results revealed that the ligands bind to DNA as: (RClBr) > (RCl2) > (RBr2) > (RI2) and (SClBr) > (SCl2) > (SBr2) > (SI2), indicating the effect of halogen on binding constant. In addition, DNA-binding constant of the S and R-enantiomers are different from each other. The ligands can form halogen bonds with DNA that were confirmed by molecular docking. This method was also measured the bond distances and bond angles. The study of obtained data can have concluded that binding affinity of the ligands to DNA depends on strength of halogen bonds. The potential anticancer activity of ligands were also evaluated on MCF-7 and HeLa cancer cell lines by using MTT assay. The results showed that the anticancer activity and FS-DNA interaction is significantly dependent on the stereoisomers of Schiff base compounds as R-enantiomers displayed significantly higher activity than S-enantiomers. The molecular docking was also used to illustrate the specific DNA-binding of synthesized compounds and groove binding mode of DNA interaction was proposed for them. In addition, molecular docking results indicated that there are three types of bonds (H and X-bond and hX-bond) between synthesized compounds and base pairs of DNA.

Probing the interaction of the phytochemical 6-gingerol from the spice ginger with DNA

6-Gingerol [5-hydroxy-1-(4-hydroxy-3-methoxyphenyl) decan-3-one], the bio-active ingredient of the popular Indian spice ginger (Zingiber officinale Roscoe), is well-known for its pharmacological and physiological actions. The potent antioxidant, antiemetic, antiulcer, antimicrobial, analgesic, hypoglycemic, antihypertensive, antihyperlipidemic, immunostimulant, anti-inflammatory, cardiotonic, and cancer prevention activities of 6-Gingerol has been investigated and explored. 6-Gingerol is a good candidate for the treatment of various cancers including prostrate, pancreatic, breast, skin, gastrointestinal, pulmonary, and renal cancer. In this study we report for the first time the molecular recognition of 6-Gingerol with calf thymus DNA (ctDNA) through experimental and molecular modeling techniques confirming a minor groove binding mode of 6-Gingerol with ctDNA. Fluorescence and UV–vis spectroscopic studies confirm the complex formation of 6-gingerol with ctDNA. The energetics and thermodynamics of the interaction of 6-Gingerol with ctDNA was explored by Isothermal Titration Calorimetry (ITC) and Differential Scanning Calorimetry (DSC). The ctDNA helix melting upon 6-Gingerol binding was examined by melting temperature Tm analysis. Further the electrophoretic mobility shift assay confirms a possible groove binding of 6-Gingerol with ctDNA. Molecular docking and Molecular dynamics (MD) studies provide a detailed understanding on the interaction of 6-Gingerol binding in the minor groove of DNA which supports experimental results.

A copper(II) complex of 6-(pyrazin-2-yl)-1,3,5-triazine-2,4-diamine and L-serinate: synthesis, crystal structure, DNA-binding and molecular docking studies

A water-soluble Cu(II) complex, [Cu(pzta)(L-Ser)(ClO4)]·1.5H2O (pzta = 6-(pyrazin-2-yl)-1,3,5-triazine-2,4-diamine; L-Ser = L-serinate), was synthesized and characterized by analytical and spectral techniques. In addition, the molecular structure of the complex was confirmed by single-crystal X-ray diffraction, revealing that the central Cu(II) atom was located in a six-coordinate distorted octahedral geometry. Multi-spectroscopic methods, viscosity measurements and thermal denaturation experiments revealed that the complex binds to DNA with apparent binding constant of 2.93 × 103 M−1 through a groove binding mode. The positive values of ΔH and ΔS obtained from isothermal titration calorimetry experiments indicated that hydrophobic interactions play an important role in the formation of the complex–DNA adduct. Molecular docking studies were carried out to better understand the binding mode of the complex with DNA.

Synthesis, molecular docking and DNA binding studies of phthalimide-based copper(II) complex: In vitro antibacterial, hemolytic and antioxidant assessment

In the present research work, we prepared N-substituted phthalimide, 2-(-(2-(2-(2-(1,3-dioxoisoindoline-2-yl-ethylamino)ethylamino)ethyl)isoindoline-1,3-dione (DEEI) and its copper(II) complex. The ligand (DEEI) and its Cu(II) complex were structurally identified using absorption, FTIR, NMR, electron spin resonance, X-ray diffraction spectral studies, thermogravimetric and elemental analyses. The electronic spectrum and magnetic moment value proposed that Cu(II) complex has square planar geometry. The DNA interaction ability of the ligand (DEEI) and Cu(II) complex was studied by means of absorption and fluorescence spectrophotometer, viscosity measurements, cyclic voltammetery, and circular dichroism methods. The extent of DNA binding (Kb) with Calf thymus (Ct-DNA) follows the order of Cu(II) complex (1.11 × 106 M−1) > DEEI (1.0 × 105 M−1), indicating that Cu(II) complex interact with Ct-DNA through groove binding mode and more sturdily than ligand (DEEI). Interestingly, in silico predictions were corroborated with in vitro DNA binding studies. The antibacterial evaluation of these compounds was screened against a panel of bacterial strains Pseudomonas aeruginosa (MTCC 2453), Salmonella enterica (MTCC 3224), Streptococcus pneumoniae (MTCC 655), Enterococcus faecalis (MTCC 439), Klebsiella pneumonia and Escherichia coli (ATCC 25922). The results showed that the copper(II) complex has significant antibacterial potential (IC50 = 0.0019 μg/mL) against Salmonella enteric comparable with ligand (DEEI) and standard drug ciprofloxacin. Growth curve study of Cu(II) complex against only three bacterial strains S. enterica, E. faecalis and S. pneumoniae showed its bactericidal nature. Cu(II) complex showed less than 2% hemolysis on human RBCs indicating its non toxic nature. The results of antioxidant assay demonstrated that scavenging activity of Cu(II) complex is higher as compared to ligand and ascorbic acid as standard.

Binding Mode of Cationic Porphyrin with CT-DNA: Importance of the Location and the Number of Positively Charged of Periphery Cationic Ions of Porphyrin.

The binding modes of o-, m-, and p-trans-BMPyP with DNA were studied using their spectroscopic properties. Also, the binding modes were compared based on the location and number of periphery cationic methylpyridine ions of the cationic porphyrins. The optical absorption spectra of the o-, m-, and p-trans-BMPyP when bound to DNA presented red shifts and hypochromicity compared to the optical absorption spectrum of DNA-free cationic porphyrins. m-trans-BMPyP–DNA presented the largest red shifts and hypochromicity. The results of the circular dichroism spectral analysis indicated positive and negative bisignate absorption bands in the Soret band of the porphyrins in the case of all concentration ratios of o- and p-trans-BMPyP–DNA, and two negative absorption bands were observed in m-trans-BMPyP–DNA. Compared to the size of the absorption band of the DNA optical absorption spectrum, the results of the reduced linear (LDr) spectral analysis indicated mainly small sizes of Soret absorption bands (the absorption spectrum of porphyrins) and positive LDr values for o- and p-trans-BMPyP–DNA. In consideration of several of such spectroscopic properties, the binding of o- and p-trans-BMPyP with DNA can be said to be distant to insertion modes. Although the case of m-trans-BMPyP to DNA is an insertion mode, the m-trans-BMPyP molecular surface presented much tilt within the intercalation pocket. The results of comparing the binding modes of TMPyP having four periphery cationic methylpyridine ions of cationic porphyrin indicated that regardless of the number of periphery cationic methylpyridine ions of cationic porphyrin, in the case of the ortho-position, nonplanarity due to steric hindrance of the periphery cationic methylpyridine ions presented outside or groove-binding modes indicative of interaction with DNA phosphates. Unlike the ortho-position, the para-position presented different binding modes based on the number of periphery cationic methylpyridine ions. Only cationic porphyrins having four periphery cationic methylpyridine ions were inserted into the DNA. Lastly, regardless of the number of periphery cationic methylpyridine ions, all meta-positions were inserted into the DNA. This indicated that at the least the location and the number of periphery cationic methylpyridine ions of the porphyrins used in this experiment were important elements that determine insertion into DNA base pairs.

Synthesis of a new Pt(II) complex containing valganciclovir drug and calf-thymus DNA interaction study using multispectroscopic methods

A new complex, [Pt(valcyte)(DMSO)Cl]Cl, in which valcyte (trade name) served as valganciclovir hydrochloride drug ([2-[(2-amino-6-oxo-3H-purin-9-yl)methoxy]-3-hydroxypropyl](2S)-2-amino-3-methylbutanoate), was synthesized and characterized by different physicochemical methods. Binding interaction of this complex with calf-thymus DNA (ct-DNA) has been investigated by multispectroscopic techniques. The complex displays significant binding properties with ct-DNA. The results of fluorescence and UV–vis absorption spectroscopy indicated that this complex interacted with ct-DNA in a groove-binding mode, and the binding constant was 3.8 × 104 M−1. Furthermore, the complex induced detectable changes in the CD spectrum of ct-DNA and slightly changed its viscosity which verified the groove-binding mode. Finally, all results indicated that Pt(II) complex interact with DNA via groove-binding mode.

Spectroscopic investigation on the interaction of DNA with superparamagnetic iron oxide nanoparticles doped with chromene via dopamine as cross linker

Objective(s): The interaction of DNA with iron oxide nanoparticles (SPIONs) was studied to find out the interaction mechanism and design new drug delivery systems. Materials and Methods: The interaction of calf thymus DNA (ctDNA) with SPIONs doped with 2H-chromene via dopamine as cross linker (SPIONs@DA-Chr) was studied using the UV absorption spectroscopy, viscosity measurement, circular dichroism, fluorescence and FT-IR spectroscopic techniques. Results: UV absorption study showed hyperchromic effect in the spectra of DNA. Few changes were observed in the viscosity of ctDNA in the presence of different concentration of SPIONs@DA-Chr. The result of circular dichroism (CD) suggested that SPIONs@DA-Chr can change the secondary structure of DNA. Further, fluorescence quenching reaction of ctDNA with SPIONs@DA-Chr and competitive fluorescence spectroscopy studied by using methylene blue, have shown that the SPIONs@DA-Chr can bind to ctDNA through non-intercalative mode. FT-IR spectroscopy confirmed the binding of SPIONs@DA-Chr and ctDNA. Conclusion: These results suggested that SPIONs@DA-Chr binds to DNA via groove binding mode.

Non-covalent interaction between CA–TAT and calf thymus DNA: Deciphering the binding mode by in vitro studies

CA–TAT, a novel peptide analog, was modified at the N-terminus of TAT (47–57), the cell-penetrating peptide transacting activator of transcription, by attaching cecropin A (1–7). CA–TAT, TAT (47–57), and cecropin A (1–7) were synthesized using standard Fmoc solid-phase peptide synthesis procedures, purified using reversed-phase high performance liquid chromatography (RP–HPLC), and characterized using ESI–MS. CA–TAT demonstrated antibacterial activities against bacteria with low hemolysis (MHC > 128 μM). The minimum inhibitory concentration (MIC) values of CA–TAT were in the range of 1–16 μM, which completely inhibited both gram-positive and gram-negative bacteria. The interactions between CA–TAT or TAT (47–57) and calf thymus DNA (ct-DNA) were investigated using multi-spectroscopic techniques and viscometry. The results showed that both CA–TAT and TAT (47–57) can interact with DNA via the minor groove-binding mode, and binding constant was calculated to be 2.83 × 105 L mol−1 at 310 K, which is lower than that with the classical intercalation binder ethidium bromide (EB). Compared with TAT (47–57) or cecropin A (1–7), CA–TAT combined with DNA much closer. The study results suggest that CA–TAT can be used as a novel antibacterial peptide in the development of new antibiotics because of its antibacterial activity that targets intracellular DNA.

Multi-spectroscopic and molecular docking studies on the interaction of darunavir, a HIV protease inhibitor with calf thymus DNA

Molecular interaction of darunavir (DRV), a HIV protease inhibitor with calf thymus deoxyribonucleic acid (ct-DNA) was studied in physiological buffer (pH7.4) by multi-spectroscopic approaches hand in hand with viscosity measurements and molecular docking technique. The UV absorption and fluorescence results together revealed the formation of a DRV–ct-DNA complex having binding affinities of the order of 103M−1, which was more in keeping with the groove binding. The results that DRV bound to ct-DNA via groove binding mode was further evidenced by KI quenching studies, viscosity measurements, competitive binding investigations with EB and Rhodamine B and CD spectral analysis. The effect of ionic strength indicated the negligible involvement of electrostatic interaction between DRV and ct-DNA. The thermodynamic parameters regarding the binding interaction of DRV with ct-DNA in terms of enthalpy change (ΔH0) and entropy change (ΔS0) were −63.19kJ mol−1 and −141.92J mol−1K−1, indicating that hydrogen bonds and van der Waals forces played a predominant role in the binding process. Furthermore, molecular simulation studies suggested that DRV molecule was prone to bind in the A-T rich region of the minor groove of DNA.

Improving activity of anticancer oxalipalladium analog by the modification of oxalate group with isopentylglycine

In this article, we describe the influence of structure on biological behavior of amino acid-Pd complex and compare it with oxalipalladium. A new water-soluble oxalipalladium analog with formula of [Pd(DACH)(isopentylgly)](NO3), where DACH is 1R,2R-diaminocyclohexane, has been synthesized and characterized by elemental analysis, conductivity measurements, IR, UV–Vis, and 1H NMR spectroscopies. The interactions of oxalipalladium and its amino acid derivative with highly polymerized calf-thymus DNA have been extensively studied by spectroscopic methods. The high binding constants of oxalipalladium (0.38 × 104 M−1) and new amino acid-Pd complex (0.65 × 104 M−1) were determined using absorption measurements. Also circular dichroism (CD) studies show that Pd complex causes more disturbances on DNA structure rather than oxalipalladium. The experimental results proposed that [Pd(DACH)(isopentylgly)](NO3) is bound to DNA by groove-binding mode as well as partially covalent interaction, while oxalate analog binds covalently to DNA after hydrolysis. Interaction of the two metal derivative complexes was studied by molecular docking simulation. The results showed that amino acid-Pd complex has higher negative docking energy and higher tendency for interaction with DNA, and exert more structural change on DNA. Finally, the anticancer and growth inhibitory activities of synthesized complexes were investigated against human colon cancer cell line of HCT116 after 24 h incubation time using MTT assay. Results show that the complex [Pd(DACH)(isopentylgly)](NO3) showed enhanced anticancer and growth inhibitory activities against human colon can cell line HCT116.

Probing the Binding Pathway of BRACO19 to a Parallel-Stranded Human Telomeric G-Quadruplex Using Molecular Dynamics Binding Simulation with AMBER DNA OL15 and Ligand GAFF2 Force Fields.

Human telomeric DNA G-quadruplex has been identified as a good therapeutic target in cancer treatment. G-quadruplex-specific ligands that stabilize the G-quadruplex have great potential to be developed as anticancer agents. Two crystal structures (an apo form of parallel stranded human telomeric G-quadruplex and its holo form in complex with BRACO19, a potent G-quadruplex ligand) have been solved, yet the binding mechanism and pathway remain elusive. In this study, we simulated the binding of a free BRACO19 molecule to the apo form of the G-quadruplex using the latest AMBER DNA (OL15) and ligand (GAFF2) force fields. Three binding modes have been identified: top stacking, bottom intercalation, and groove binding. Bottom intercalation (51% of the population) resembles the bottom binding pose in the complex crystal structure very well. The groove binding mode is less stable than the bottom binding mode and is likely to be an intermediate state leading to the bottom binding mode. A flip-insertion mechanism was observed in the bottom intercalation mode, during which flipping of the bases outward makes space for ligand insertion, after which the bases flip back to increase the stability of the complex. In addition to reproducing the base-flipping behavior for some loop residues upon ligand binding, the direct alignment type of the ATAT-tetrad was observed in our simulations for the first time. These successes provide initial support for using this combination of the OL15 and GAFF2 force fields to study quadruplex-ligand interactions.

Thermodynamics of interaction ofmeso-tetra-(4N-oxyethylpyridyl) porphyrin and its Cu(II)- and Co(II)- containing derivatives with A and B forms of DNA

The interaction of water soluble meso-tetra-(4N-oxyethylpyridyl) porphyrin (TOEPyP4) and its Cu(II)- and Co(II)-containing derivatives (CuTOEPyP4 and CoTOEPyP4) with A and B forms of DNA at low ionic strength was studied via UV-vis spectrophotometry and Circular Dichroism. It is shown that the binding constant of TOEPyP4 and CuTOEPyP4 with A–DNA is two times larger than with B–DNA, and the binding constant of CoTOEPyP4 does not depend on the form of DNA. The thermodynamical analysis based on spectral data indicates the preferable entropic character of porphyrins binding with both forms of DNA. This result shows that at low ionic strength the external groove binding mode is a preferred binding mechanism of these porphyrins with both forms of DNA.

Binding Studies of Isoxsuprine Hydrochloride to Calf Thymus DNA Using Multispectroscopic and Molecular Docking Techniques.

In the present work, the interaction of Isoxsuprine (ISX) with Calf thymus DNA (ct-DNA) under physiological conditions (Tris-HCl buffer of pH 7.4) was investigated by using electronic absorption, circular dichroism, viscosity, electrochemical studies, fluorescence techniques, salt effect studies and computational studies. Competitive fluorimetric studies with Hoechst 33258 have shown that ISX exhibit the ability to displace the DNA-bound Hoechst 33258, indicating that it binds to ct-DNA in strong competition with Hoechst 33258 for the minor groove binding. Furthermore, the resulting data showed that ISX cannot displace methylene blue or acridine orange, which are the common intercalator molecules. The viscosity of ct-DNA solution was almost unchanged on addition of ISX and circular dichroism (CD) spectra of ct-DNA showed small changes in the presence of ISX which is in agreement with groove binding mode of interaction. Thus all above studies showed that the ISX drug binds to ct-DNA in a groove binding mode.The salt-effect studies showed the non-electrostatic nature of binding of ISX to ct-DNA. Moreover, molecular docking results support the above experimental data and suggest that ISX prefers to bind on the minor groove of ct-DNA.

Molecular modeling of cationic porphyrin-anthraquinone hybrids as DNA topoisomerase IIβ inhibitors

Human DNA Topoisomerase II has been regarded as a promising target in anticancer drug discovery. In the present study, we designed six porphyrin-anthraquinone hybrids bearing pyrazole or pyridine group as meso substituents and evaluated their potentials as DNA Topoisomerase IIβ inhibitor. First, we investigated the binding orientation of porphyrin hybrids into DNA topoisomerase IIβ employing AutoDock 4.2 and then performed 20-ns molecular dynamics simulations to see the dynamic stability of each porphyrin-Topo IIβ complex using Amber 14. We found that the binding of porphyrin hybrids occured through intercalation and groove binding mode in addition interaction with the amino acid residues constituting the active cavity of Topo IIβ. Each porphyrin-Topo IIβ complex was stabilized during 20-ns dynamics simulations. The MM-PBSA free energy calculation shows that the binding affinities of porphyrin hybrids were modified with the number of meso substituent. Interestingly, the affinity of all porphyrin hybrids to Topo IIβ was stronger than that of native ligand (EVP), indicating the potential of the designed porphyrin to be considered in experimental research.

Synthesis and bioelectrochemical behavior of aromatic amines

Four aromatic amines 1-amino-4-phenoxybenzene (A1), 4-(4-aminophenyloxy) biphenyl (A2), 1-(4-aminophenoxy) naphthalene (A3) and 2-(4-aminophenoxy) naphthalene (A4) were synthesized and characterized by elemental, spectroscopic (FTIR, NMR), mass spectrometric and single crystal X-ray diffraction methods. The compounds crystallized in monoclinic crystal system with space group P21. Intermolecular hydrogen bonds were observed between the amine group and amine/ether acceptors of neighboring molecules. Electrochemical investigations were done using cyclic voltammetry (CV), square wave voltammetry (SWV) and differential pulse voltammetry (DPV). CV studies showed that oxidation of aromatic amines takes place at about 0.9 V (vs. Ag/AgCl) and the electron transfer (ET) process has irreversible nature. After first scan reactive intermediate were generated electrochemically and some other cathodic and anodic peaks also appeared in the succeeding scans. DPV study revealed that ET process is accompanied by one electron. DNA binding study of aromatic amines was performed by CV and UV–visible spectroscopy. These investigations revealed groove binding mode of interaction of aromatic amines with DNA.

The Interaction Mode of Groove Binding Between Quercetin and Calf Thymus DNA Based on Spectrometry and Simulation.

Quercetin, a ubiquitous flavanoid, has numerous pharmacological effects, such as antioxidant and antitumor. Previous studies showed nucleic acids were the potential biological targets for antitumor medicine. For exploring the mechanism of DNA-target medicine, the interaction between quercetin and calf thymus DNA was studied based on the method of spectrometry and simulation in our study. Firstly, the interaction between quercetin and calf thymus DNA was confirmed by fluorescence spectrometry. Furthermore, circular dichroism, fluorescence polarization, competitive displacement assay, and salt concentration dependence assay were applied to search the interaction mode of quercetin-calf thymus DNA, which proved the existence of groove binding and electrostatic interaction. Meanwhile, quenching constant Ksv , binding constant Ka and the number of binding sites n was calculated, inferring that the fluorescence quenching occurred by static quenching process, and the main acting force was hydrogen bond. Finally, molecular docking was used to simulate and analyze the interaction between quercetin and calf thymus DNA.

Synthesis, characterization and biological screening studies of mixed ligand complexes using flavonoids as precursors

Flavonoids are a group of plant phenolics that provide various health benefits through cell signalling pathways and antioxidant effects. In the present study, a new series of mixed ligand complexes of Co(II), Ni(II), Cu(II) and Zn(II) were synthesized by incorporating curcumin and quercetin flavonoid precursors. The structural features of the synthesized complexes were explored using elemental analysis, thermogravimetric analysis, UV–visible, infrared, NMR, mass and electron paramagnetic resonance spectral analyses and conductivity measurements. These data support an octahedral geometry of the synthesized complexes. In silico biological activity score for the ligand was predicted using PASS online software. ADMET properties were studied using VLS3D online software. Anti‐inflammatory and antioxidant activities were experimentally validated which prove that theoretical predictions are in agreement with the experimental results. Interestingly the synthesized complexes interact with calf thymus DNA through groove binding mode. Moreover, they have good potential to cleave pUC19 DNA. Minimum inhibitory concentration values of the synthesized complexes reveal that they have better antimicrobial efficacy than the ligands.

Synthesis, spectral characterization, theoretical, antimicrobial, DNA interaction and in vitro anticancer studies of Cu(II) and Zn(II) complexes with pyrimidine-morpholine based Schiff base ligand

Novel Cu(II) (1) and Zn(II) (2) complexes with 4-(1-(4-morpholinophenyl)ethylideneamino)pyrimidine-5-carbonitrile) (L) have been synthesized and characterized by various spectroscopic and analytical techniques. DFT (density functional theory) studies result confirms that, LMCT mechanism have been done between L and M(II) ions. The antimicrobial studies indicate that the ligand L and complexes 1 &2 exhibit higher activity against the E. coli bacteria and C. albicans fungi. The groove binding mode of ligand L and complexes 1 &2 with CT-DNA have been confirmed by electronic absorption, competitive binding, viscometric and cyclic voltammetric studies. The electronic absorption titration of ligand L and complexes 1 &2 with DNA have been carried out in different buffer solutions (pH 4.0, 7.0 & 10.0). The Kb values of ligand L and complexes 1 &2 are higher in acidic buffer at pH 4.0 (Kb=2.42×105, L; 2.8×105, 1; 2.65×105, 2) and the results revealed that, the interaction of synthesized compounds with DNA were higher in the acidic medium than basic and neutral medium. Furthermore, CT-DNA cleavage studies of ligand L and complexes 1 &2 have been studied. The in vitro anticancer activities results show that complexes 1 &2 have moderate cytotoxicity against cancer cell lines and low toxicity on normal cell line than ligand L.

Monomeric and Dimeric Oxidomolybdenum(V and VI) Complexes, Cytotoxicity, and DNA Interaction Studies: Molybdenum Assisted C═N Bond Cleavage of Salophen Ligands.

Four novel dimeric bis-μ-imido bridged metal-metal bonded oxidomolybdenum(V) complexes [MoV2O2L'21-4] (1-4) (where L'1-4 are rearranged ligands formed in situ from H2L1-4) and a new mononuclear dioxidomolybdenum(VI) complex [MoVIO2L5] (5) synthesized from salen type N2O2 ligands are reported. This rare series of imido-bridged complexes (1-4) have been furnished from rearranged H3L'1-4 ligands, containing an aromatic diimine (o-phenylenediamine) "linker", where Mo assisted hydrolysis followed by -C═N bond cleavage of one of the arms of the ligand H2L1-4 took place. A monomeric molybdenum(V) intermediate species [MoVO(HL'1-4)(OEt)] (Id1-4) was generated in situ. The concomitant deprotonation and dimerization of two molybdenum(V) intermediate species (Id1-4) ultimately resulted in the formation of a bis-μ-imido bridge between the two molybdenum centers of [MoV2O2L'21-4] (1-4). The mechanism of formation of 1-4 has been discussed, and one of the rare intermediate monomeric molybdenum(V) species Id4 has been isolated in the solid state and characterized. The monomeric dioxidomolybdenum(VI) complex [MoVIO2L5] (5) was prepared from the ligand H2L5 where the aromatic "linker" was replaced by an aliphatic diimine (1,2-diaminopropane). All the ligands and complexes have been characterized by elemental analysis, IR, UV-vis spectroscopy, NMR, ESI-MS, and cyclic voltammetry, and the structural features of 1, 2, 4, and 5 have been solved by X-ray crystallography. The DNA binding and cleavage activity of 1-5 have been explored. The complexes interact with CT-DNA by the groove binding mode, and the binding constants range between 103 and 104 M-1. Fairly good photoinduced cleavage of pUC19 supercoiled plasmid DNA was exhibited by all the complexes, with 4 showing the most promising photoinduced DNA cleavage activity of ∼93%. Moreover, in vitro cytotoxic activity of all the complexes was evaluated by MTT assay, which reveals that the complexes induce cell death in MCF-7 (human breast adenocarcinoma) and HCT-15 (colon cancer) cell lines.

Synthesis, crystal structures and DNA/human serum albumin binding of ternary Cu(II) complexes containing amino acids and 6‐(pyrazin‐2‐yl)‐1,3,5‐triazine‐2,4‐diamino

Two water‐soluble 6‐(pyrazin‐2‐yl)‐1,3,5‐triazine‐2,4‐diamino (pzta)‐based Cu(II) complexes, namely [Cu(l‐Val)(pzta)(H2O)]ClO4 (1) and [Cu(l‐Thr)(pzta)(H2O)]ClO4 (2) (l‐Val: l‐valinate; l‐Thr: l‐threoninate), were synthesized and characterized using elemental analyses, molar conductance measurements, spectroscopic methods and single‐crystal X‐ray diffraction. The results indicated that the molecular structures of the complexes are five‐coordinated and show a distorted square‐pyramidal geometry, in which the central copper ions are coordinated to N,N atoms of pzta and N,O atoms of amino acids. The interactions of the complexes with DNA were investigated using electronic absorption, competitive fluorescence titration, circular dichroism and viscosity measurements. These studies confirmed that the complexes bind to DNA through a groove binding mode with certain affinities (Kb = 4.71 × 103 and 1.98 × 103 M−1 for 1 and 2, respectively). The human serum albumin (HSA) binding properties of the complexes were also evaluated using fluorescence and synchronous fluorescence spectroscopies, indicating that the complexes could quench the intrinsic fluorescence of HSA in a static quenching process. The relevant thermodynamic parameters revealed the involvement of van der Waals forces and hydrogen bonds in the formation of complex–HSA systems. Finally, molecular docking technology was also used to further verify the interactions of the complexes with DNA/HSA.