Synthesis,characterization and nucleic acid binding studies of mononuclear copper(II) complexes derived from azo containing O,O donor ligands

Abstract

Azo linked salicyldehyde and a new 2-hydroxy acetophenone based ligands (HL¹ and HL²) with their copper(II) complexes [Cu(L¹)₂] (1) and [Cu(L²)₂] (2) were synthesized and characterized by spectroscopic methods such as ¹H, 13C NMR, UV–Vis spectroscopy and elemental analyses. Calculation based on Density Functional Theory (DFT), have been performed to obtain optimized structures. Binding studies of these copper (II) complexes with calf thymus DNA (ct-DNA) and torula yeast RNA (t-RNA) were analyzed by absorption spectra, emission spectra and Viscosity studies and Molecular Docking techniques. The absorption spectral study indicated that the copper(II) complexes of 1 and 2 had intrinsic binding constants with DNA or RNA in the range of 7.6?±?0.2?×?10³?M^?1 or 6.5?±?0.3?×?10³M^?1 and 5.7?±?0.4?×?10⁴ M^?1 or 1.8?±?0.5?×?10³ M^?1 respectively. The synthesized compounds and nucleic acids were simulated by molecular docking to explore more details mode of interaction of the complexes and their orientations in the active site of the receptor.     

Structure-activity relationship on DNA binding and anticancer activities of a family of mixed-ligand oxidovanadium(V) hydrazone complexes

The title family of mixed-ligand oxidovanadium(V) hydrazone complexes are [V^VO(HL¹)(hq)] (1) and [V^VO(HL²)(hq)] (2), where (HL¹)^2? and (HL²)^2? are the dinegative form of 2-hydroxybenzoylhydrazone of acetylacetone (H₃L¹) and benzoylacetone (H₃L²), respectively, and hq^? is the mononegative form of 8-hydroxyquinoline (Hhq). Complexes were used to determine their binding constant with CT DNA using various spectroscopic techniques namely, electronic absorption, fluorescence and circular dichroism spectroscopy. The binding constant values suggest the intercalative mode of binding with the CT DNA and follow the order: 2 > 1. The bulky size as well as electron withdrawing property of the phenyl group (which is present in the β-diketone part of the hydrazone moiety in complex 2 in place of a CH₃ group in complex 1) is responsible for the higher activity of 2 than 1. Complexes were screened for cytotoxic activity on cervical cancer cells and were found to be potentially active (IC₅₀ value for 1 and 2 is 33 and 29 μM, respectively), even better than the widely used cis-platin (IC₅₀ = 63.5 μM) and carboplatin (IC₅₀ = > 200 μM) which is evident from the respective IC₅₀ value. Nuclear staining experiment suggests that these complexes kill the SiHa cancer cells through apoptotic mode. The molecular docking study also suggested the intercalative mode of binding of these complexes with CT DNA and HPV 18 DNA.     

Evolution of 1, 3, 5-trisubstituted bipyrazole scaffold based platinum(II) complexes as a biological active agent

Abstract

Square planar mononuclear platinum(II) complexes having general formula [Pt(Lⁿ)Cl₂], (where, Lⁿ?=?L^1–4) were synthesized with neutral bidentate heterocyclic 1,3,5-trisubstituted bipyrazole based ligands. The synthesized compounds were characterized by physicochemical method such as TGA, molar conductance, micro-elemental analysis and magnetic moment, and spectroscopic method such as, FT-IR, UV–vis, ¹H NMR, ¹³C NMR and mass spectrometry. Biological applications of the compounds were carried out using in vitro brine shrimp lethality bioassay, in vitro antimicrobial study against five different pathogens, and cellular level cytotoxicity against Schizosaccharomyces pombe (S. Pombe) cells. Pt(II) complexes were tested for DNA interaction activities using electronic absorption titration, viscosity measurements study, fluorescence quenching technique and molecular docking assay. Binding constants (K_b) of ligands and complexes were observed in the range of 0.23–1.07?×?10⁵?M^?1 and 0.51–3.13?×?10⁵?M^?1, respectively. Pt(II) complexes (I–IV) display an excellent binding tendency to biomolecule (DNA) and possess comparatively high binding constant (K_b) values than the ligands. The DNA binding study indicate partial intercalative mode of binding in complex-DNA. The gel electrophoresis activity was carried out to examine DNA nuclease property of pUC19 plasmid DNA.     

Multi-spectroscopic and voltammetric evidences for binding,conformational changes of bovine serum albumin with thiamine

The interaction between thiamine hydrochloride (TA) and bovine serum albumin (BSA) was investigated by fluorescence, FTIR, UV–vis spectroscopic and cyclic voltammetric techniques under optimised physiological condition. The fluorescence intensity of BSA is gradually decreased upon addition of TA due to the formation of a BSA–TA complex. The binding parameters were evaluated and their behaviour at different temperatures was analysed. The quenching constants (K_sv) obtained were 2.6 × 10⁴, 2.2 × 10⁴ and 2.0 × 10⁴ L mol^?1 at 288, 298 and 308 K, respectively. The binding mechanism was static-type quenching. The values of ΔH° and ΔS° were found to be 26.87 kJ mol^?1 and 21.3 J K^?1 mol^?1, and indicated that electrostatic interaction was the principal intermolecular force. The changes in the secondary structure of BSA upon interaction with TA were confirmed by synchronous and 3-D spectral results. Site probe studies reveal that TA is located in site I of BSA. The effects of some common metal ions on binding of BSA–TA complex were also investigated.     

Study on the interaction of fisetholz with BSA/HSA by multi-spectroscopic,cyclic voltammetric,and molecular docking technique

The interaction of fisetholz with bovine serum albumin (BSA) and human serum albumin (HSA) was investigated by multi-spectroscopic, cyclic voltammetric, and molecular docking technique. The results revealed that there was a static quenching of BSA/HSA induced by fisetholz. The binding constants (K_a) and binding sites (n) were calculated at different temperatures (293, 303, and 311?K). The enthalpy change (ΔH) were calculated to be –17.20?kJ mol^?1 (BSA) and –18.28?kJ mol^?1 (HSA) and the entropy change (ΔS) were calculated to be 35.41?J mol^?1 (BSA) and 24.02?J mol^?1 (HSA), respectively, which indicated that the interaction between fisetholz and BSA/HSA was mainly by electrostatic attraction. Based on displacement experiments using site probes, indomethacin and ibuprofen, the binding site of fisetholz to BSA/HSA was identified as sub-domain IIIA, which was further confirmed by molecular docking method. There was little effect of K⁺, Ca²⁺, Cu²⁺, Zn²⁺, and Fe³⁺ on fisetholz-BSA or fisetholz-HSA complex. The spectra of synchronous fluorescence, circular dichroism (CD) and Fourier transform infrared (FT-IR) all showed that fisetholz binding to BSA/HSA leads to secondary structures change of the two serum albumins. According to the Förster non-radiation energy transfer theory, the binding distance between fisetholz and BSA/HSA was 2.94/4.68?nm. The cyclic voltammetry as a supporting tool also indicated that fisetholz interacted with protein.

Communicated by Ramaswamy H. Sarma     

Tris-chelated complexes of nickel(II) with bipyridine derivatives: DNA binding and cleavage,BSA binding,molecular docking,and cytotoxicity

Abstract

Two nickel(II) complexes with substituted bipyridine ligand of the type [Ni(NN)₃](ClO₄)₂, where NN is 4,4′-dimethyl-2,2′-bipyridine (dimethylbpy) (1) and 4,4′-dimethoxy-2,2′-bipyridine (dimethoxybpy) (2), have been synthesized, characterized, and their interaction with DNA and bovine serum albumin (BSA) studied by different physical methods. X-ray crystal structure of 1 shows a six-coordinate complex in a distorted octahedral geometry. DNA-binding studies of 1 and 2 reveal that both complexes sit in DNA groove and then interact with neighboring nucleotides differently; 2 undergoes a partial intercalation. This is supported by molecular-docking studies, where hydrophobic interactions are apparent between 1 and DNA as compared to hydrogen bonding, hydrophobic, and π–π interactions between 2 and DNA minor groove. Moreover, the two complexes exhibit oxidative cleavage of supercoiled plasmid DNA in the presence of hydrogen peroxide as an activator in the order of 1?>?2. In terms of interaction with BSA, the results of spectroscopic methods and molecular docking show that 1 binds with BSA only via hydrophobic contacts while 2 interacts through hydrophobic and hydrogen bonding. It has been extensively demonstrated that the nature of the methyl- and methoxy-groups in ligands is a strong determinant of the bioactivity of nickel(II) complexes. This may justify the above differences in biomolecular interactions. In addition, the in vitro cytotoxicity of the complexes on human carcinoma cells lines (MCF-7, HT-29, and U-87) has been examined by MTT assay. According to our observations, 1 and 2 display cytotoxicity activity against selected cell lines.

Communicated by Ramaswamy H. Sarma     

Metal complexes of naphthoquinone based ligand: synthesis,characterization, protein binding,DNA binding/cleavage and cytotoxicity studies

Protein binding, DNA binding/cleavage and in vitro cytotoxicity studies of 2-((3-(dimethylamino)propyl)amino)naphthalene-1,4-dione (L) and its four coordinated M(II) complexes [M(II) = Co(II), Cu(II), Ni(II) and Zn(II)] have been investigated using various spectral techniques. The structure of the ligand was confirmed by spectral and single crystal XRD studies. The geometry of the complexes has been established using analytical and spectral investigations. These complexes show good binding tendency to bovine serum albumin (BSA) exhibiting high binding constant values (10⁵ M^?1) when compared to free ligand. Fluorescence titration studies reveal that these compounds bind strongly with CT-DNA through intercalative mode (K_app 10⁵ M^?1) and follow the order: Cu(II) > Zn(II) > Ni(II) > Co(II) > L. Molecular docking study substantiate the strength and mode of binding of these compounds with DNA. All the complexes efficiently cleaved pUC18-DNA via hydroxyl radical mechanism and the Cu(II) complex degraded the DNA completely by converting supercoiled form to linear form. The complexes demonstrate a comparable in vitro cytotoxic activity against two human cancer cell lines (MCF-7 and A-549), which is comparable with that of cisplatin. AO/EB and DAPI staining studies suggest apoptotic mode of cell death, in these cancer cells, with the compounds under investigation.     

Detection of interaction between lysionotin and bovine serum albumin using spectroscopic techniques combined with molecular modeling

A combination of fluorescence, UV–Vis absorption, circular dichroism (CD), Fourier transform infrared (FT-IR) and molecular modeling approaches were employed to determine the interaction between lysionotin and bovine serum albumin (BSA) at physiological pH. The fluorescence titration suggested that the fluorescence quenching of BSA by lysionotin was a static procedure. The binding constant at 298 K was in the order of 10⁵ L mol^?1, indicating that a high affinity existed between lysionotin and BSA. The thermodynamic parameters obtained at different temperatures (292, 298, 304 and 310 K) showed that the binding process was primarily driven by hydrogen bond and van der Waals forces, as the values of the enthalpy change (ΔH°) and entropy change (ΔS°) were found to be ?40.81 ± 0.08 kJ mol^?1 and ?35.93 ± 0.27 J mol^?1 K^?1, respectively. The surface hydrophobicity of BSA increased upon interaction with lysionotin. The site markers competitive experiments revealed that the binding site of lysionotin was in the sub-domain IIA (site I) of BSA. Furthermore, the molecular docking results corroborated the binding site and clarified the specific binding mode. The results of UV–Vis absorption, CD and FT-IR spectra demonstrated that the secondary structure of BSA was altered in the presence of lysionotin.     

Macrocyclic complexes: synthesis,characterization, antitumor and DNA binding studies

Abstract

The present paper deals with the synthesis of novel macrocyclic complexes of the type [MLX]X, where [(M?=?Co(II) (1), and Ni(II) (2) X?=?(Cl₂)]. The complexes are synthesized by the reaction of ligand(L)diquinolineno[1,3,7,9]tetraazacyclododecine-7,15-ethane(14H,16H)-benzene with the corresponding metal salts. The synthesized complexes are thoroughly characterized by elemental analysis, FT-IR, ¹H-NMR, Mass and electronic spectra. The complexes (1) and (2) were evaluated for in vitro cytotoxicity against human breast adenocarcinoma cell (MCF-7). MTT cytotoxicity studies shows both the complexes are most effective. The binding properties of these complexes with calf thymus-DNA were studied by absorption, emission spectra, viscosity measurements, and thermal denaturation studies. On binding to CT-DNA, the absorption spectrum undergoes bathochromic and hypochromic shifts. The absorption spectral results indicate that the intrinsic binding constant (K_b) are 4.8?×?10⁵?M^?1 for (1) and 3.9?×?10⁵?M^?1 for (2) respectively, suggesting that complex (1) binds more strongly to CT-DNA than complex (2). The viscosity measurement results revealed the viscosity of sonicated rod like DNA fragments increased when the complex was added to the solution of CT-DNA. The synthesized ligand and its metal complexes are screened for antibacterial and antifungal activities.     

In vitro study on binding interaction of quinapril with bovine serum albumin (BSA) using multi-spectroscopic and molecular docking methods

The binding interaction between quinapril (QNPL) and bovine serum albumin (BSA) in vitro has been investigated using UV absorption spectroscopy, steady-state fluorescence spectroscopic, synchronous fluorescence spectroscopy, 3D fluorescence spectroscopy, Fourier transform infrared spectroscopy, circular dichroism, and molecular docking methods for obtaining the binding information of QNPL with BSA. The experimental results confirm that the quenching mechanism of the intrinsic fluorescence of BSA induced by QNPL is static quenching based on the decrease in the quenching constants of BSA in the presence of QNPL with the increase in temperature and the quenching rates of BSA larger than 10¹⁰ L mol^?1 s^?1, indicating forming QNPL–BSA complex through the intermolecular binding interaction. The binding constant for the QNPL–BSA complex is in the order of 10⁵ M^?1, indicating there is stronger binding interaction of QNPL with BSA. The analysis of thermodynamic parameters together with molecular docking study reveal that the main binding forces in the binding process of QNPL with BSA are van der Waal’s forces and hydrogen bonding interaction. And, the binding interaction of BSA with QNPL is an enthalpy-driven process. Based on Förster resonance energy transfer, the binding distance between QNPL and BSA is calculated to be 2.76 nm. The results of the competitive binding experiments and molecular docking confirm that QNPL binds to sub-domain IIA (site I) of BSA. It is confirmed there is a slight change in the conformation of BSA after binding QNPL, but BSA still retains its secondary structure α-helicity.     

Spectroscopic investigations on DNA binding profile of two new naphthyridine carboxamides and their application as turn-on fluorescent DNA staining probes

Abstract

Two new 10-methoxydibenzo[b,h][1,6]naphthyridine-2-carboxamide derivatives (R1 and R2) have been synthesized and characterized using different spectral techniques. The binding of these probes with DNA was investigated using spectral (Electronic, fluorescence, ¹H NMR and circular dichroism) and molecular docking studies. These probes exhibited a strong fluorescence around 440?nm upon excitation around 380?nm. Electronic and competitive fluorescence titration studies, in HEPES [(4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid)] buffer/dimethyl sulfoxide (pH 7.4) medium, suggest that these probes bind strongly to DNA, which is substantiated by ¹H NMR study. The binding constants are calculated to be 5.3?×?10⁷ and 6.8?×?10⁶ M^?1 for R1 and R2, respectively. From the results of spectral studies, it is proposed that the mechanism of binding of these probes with DNA is through minor groove binding mode, which is further confirmed by circular dichroism and molecular docking studies. Initial cell viability screening using MTT (3-[4,5-methylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay shows that normal Vero cells are viable towards these probes at nano molar concentration, which is the concentration range employed in the present study for DNA staining (IC₅₀ in the order of 0.023?mM). The enhancement in fluorescence intensity of these probes upon binding with DNA enables the staining of DNA in agarose gel in gel electrophoresis experiment. The sensitivity of these probes is comparable with that of ethidium bromide and DNA amounts as low as 4 nano gram are detectable.

Communicated by Ramaswamy H. Sarma     

Insights into the binding interaction between copper ferrite nanoparticles and bovine serum albumin: An effect on protein conformation and activity

The binding affinity between bovine serum albumin (BSA) and copper ferrite (CuFe₂O₄) nanoparticles in terms of conformation, stability and activity of protein was studied using various spectroscopic methods. The quenching involved in BSA–CuFe₂O₄ NP interaction was static quenching as analysed by different techniques (steady‐state and time‐resolved fluorescence along with temperature‐dependent fluorescence measurements). Among all types of possible interactions, it was revealed that the major binding forces were van der Waals interaction and hydrogen bonding, which were explored from negative values of enthalpy change (?H = ?193.85 kJ mol^?1) and entropy change (?S = ?588.88 J mol^?1 K^?1). Additionally, synchronous, circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy measurements confirmed the conformational changes in BSA upon the addition of CuFe₂O₄ NP. Furthermore, thermal denaturation observations were consistent with the circular dichroism results. The interaction of CuFe₂O₄ NP with BSA decreased the esterase activity in the BSA assay, revealing the affinity of copper ferrite towards the active site of BSA.     

Synthesis,DNA/BSA binding studies and in vitro biological assay of nickel(II) complexes incorporating tridentate aroylhydrazone and triphenylphosphine ligands

Abstract

Two new nickel (II) triphenylphosphine complexes derived from tridentate aroylhydrazone ligands [H₂L¹ = 2-hydroxy-3-methoxybenzylidene)benzohydrazone and H₂L² = N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone] and triphenylphosphine were prepared and their molecular structures were determined by single crystal X-ray diffraction analysis. Both nickel(II) complexes showed slightly distorted square planar geometry with one tridentate aroylhydrazone ligand coordinated through ONO donor atoms and one triphenylphosphine ligand coordinated to the nickel center through the phosphorus atom. DNA interaction studies indicated that both complexes possessed higher affinity to herring sperm DNA (HS-DNA) than the corresponding free aroylhydrazone ligand. Molecular docking investigations showed that both complexes could bind to DNA through intercalation of the phenyl rings between adjacent base pairs in the double helix. Meanwhile, bovine serum albumin (BSA) binding studies revealed the complexes could effectively interact with BSA and change the secondary structure of BSA. Further pharmacological evaluations of the synthesized complexes by in vitro antioxidant assays demonstrated high antioxidant activity against NO· and O₂˙^? radicals. The anticancer activity of each complex was assessed through in vitro cytotoxicity assays (CCK-8 kit) toward A549 and MCF-7 cancer cell and normal L-02 cell lines. Significantly, the Ni(II) complex derived from H₂L¹ ligand was found to be more effective cytotoxic toward MCF-7cancerous cell with the IC₅₀ value equaled 9.7?μM, which showed potent cytotoxic activity over standard drug cisplatin.

Abbreviations A549 human lung carcinoma cell

BSA bovine serum albumin

CCK-8 Cell Counting Kit-8

DFT density functional theory

DNA deoxyribonucleic acid

DPPH˙ 2,2-diphenyl-1-picrylhydrazyl

H₂L¹ 2-hydroxy-3-methoxybenzylidene)benzohydrazone N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone

H₂L² N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone

HOMO highest occupied molecular orbital

IC₅₀ the 50% activity

L-02 human normal liver cell

LOMO lowest unoccupied molecular orbital (LUMO)

MCF-7 human breast carcinoma cell

NO˙ nitric oxide

O₂˙^? superoxide anion

SOD superoxide dismutase

Communicated by Ramaswamy H. Sarma     

A trigonal-prismatic Ag(I) complex and an octahedral Cu(II) complex incorporating with oxamide Ni(II) complex ligand: Syntheses, crystal structures and oxidative nuclease activities

A mononuclear macrocyclic complex Ni^IIL^3a (L^3a = dianion of 2,3-dioxo-5,6:13,14-dibenzo-9,10-cyclohexyl-7,12-bis(methoxycarbonyl)-1,4,8,11-tetraazacyclotetradeca-7,11-diene), which shows high DNA cleavage activity in the presence of H₂O₂, was reported in our previous work. Considering that many systems for natural enzyme-mediated DNA cleavage contain two or more metal active sites, two new trinuclear complexes [Cu(NiL^3a)₂(dca)₂]·2CH₃OH (abbreviated as Cu(NiL^3a)₂) and [Ag(NiL^3a)₂(NO₃)]·2CH₃OH·0.5H₂O (abbreviated as Ag(NiL^3a)₂) were synthesized in this work, where dca is the dicyanamide. The complexes were structurally characterized by single crystal X-ray analysis. The central Cu(II) or Ag(I) atom is linked to two [NiL^3a] ligands by oxamido bridges forming a trinuclear structure. In Cu(NiL^3a)₂, the central Cu(II) ion is in an octahedral coordination geometry. Whereas in Ag(NiL^3a)₂, the central Ag(I) ion is in a rarely reported trigonal-prismatic coordination geometry. The DNA cleavage behavior of the complexes in the presence of H₂O₂ was studied in detail. Comparing with the NiL^3a, the trinuclear complex Ag(NiL^3a)₂ nearly has no ability to cleave DNA, whereas Cu(NiL^3a)₂ is a much better DNA cleavage agent. Cu(NiL^3a)₂ can efficiently convert supercoiled DNA to nicked DNA with a rate constant of 0.074 ± 0.002 min⁻¹ when 40 μM Cu(NiL^3a)₂ and 0.6 mM H₂O₂ are used. The cleavage mechanism between the complex Cu(NiL^3a)₂ and plasmid DNA is likely to involve singlet oxygen as reactive oxygen species. Circular dichroism (CD) and fluorescence spectroscopy indicate that both Cu(NiL^3a)₂ and NiL^3a bind to DNA by a groove binding mode, and the binding between Cu(NiL^3a)₂ and DNA is much stronger than that between NiL^3a and DNA. The present results may provide some information for the design of efficient multinuclear artificial nucleases.     

Synthesis,DNA and protein interactions and human topoisomerase inhibition of novel Spiroacridine derivatives

Nine new spiroacridine derivatives were synthetized by introducing cyano-N-acylhydrazone group between the acridine and phenyl-substituted rings followed by spontaneous cyclization. The new compounds were assayed for their DNA binding properties, human topoisomerase IIα inhibition and bovine serum albumin (BSA) interaction. Besides, docking analysis were performed in order to better understanding the biomolecule-compounds interactions. All compounds interacted with BSA which was demonstrated by the fluorescence suppression constant of 10⁴?M^?1. Compounds with chloro and NO₂ substituents at that para-position on phenyl ring demonstrated the best results for BSA interaction. DNA binding constant determined by UV–vis data demonstrated high values for AMTAC-11 and AMTAC-14, 1.1?×?10⁸?M^?1 and 4.8?×?10⁶?M^?1, respectively, and all others presented constant values of 10⁵?M^?1. AMTAC-06 with chloro at para-position on phenyl ring presented a topoisomerase II inhibition of 84.34% in comparison to the positive controls used. Docking studies indicated that AMTAC-06 is able to intercalate the DNA base pairs at topoisomerase IIα active site, preventing DNA connection after break, in a process known as poisoning. Topoisomerase enzyme inhibition result was correlated to BSA interaction profile, since AMTAC-06 showed the best results in both analysis. The findings obtained here proved that methoxy or chloro substitution on phenyl ring at para-position is fundamental for in vitro activity of new spiroacridine derivatives, and indicates that AMTAC-06 is a promising entity and should serve as a lead compound in the development of new DNA and protein binders, as well as human topoisomerase II inhibitors.     

Spectroscopic Studies on the Interaction of Fluorine Containing Triazole with Bovine Serum Albumin

The binding of one fluorine including triazole (C₁₀H₉FN₄S, FTZ) to bovine serum albumin (BSA) was studied by spectroscopic techniques including fluorescence spectroscopy, UV–Vis absorption, and circular dichroism (CD) spectroscopy under simulative physiological conditions. Fluorescence data revealed that the fluorescence quenching of BSA by FTZ was the result of forming a complex of BSA–FTZ, and the binding constants (K _a) at three different temperatures (298, 304, and 310 K) were 1.516?×?10⁴, 1.627?×?10⁴, and 1.711?×?10⁴?mol L^?1, respectively, according to the modified Stern–Volmer equation. The thermodynamic parameters ΔH and ΔS were estimated to be 7.752 kJ mol^?1 and 125.217 J?mol^?1?K^?1, respectively, indicating that hydrophobic interaction played a major role in stabilizing the BSA–FTZ complex. It was observed that site I was the main binding site for FTZ to BSA from the competitive experiments. The distance r between donor (BSA) and acceptor (FTZ) was calculated to be 7.42 nm based on the Förster theory of non-radioactive energy transfer. Furthermore, the analysis of fluorescence data and CD data revealed that the conformation of BSA changed upon the interaction with FTZ.     

Probing into the binding interaction between medroxyprogesterone acetate and bovine serum albumin (BSA): spectroscopic and molecular docking methods

To further understand the mechanism of action and pharmacokinetics of medroxyprogesterone acetate (MPA), the binding interaction of MPA with bovine serum albumin (BSA) under simulated physiological conditions (pH 7.4) was studied using fluorescence emission spectroscopy, synchronous fluorescence spectroscopy, circular dichroism and molecular docking methods. The experimental results reveal that the fluorescence of BSA quenches due to the formation of MPA–BSA complex. The number of binding sites (n) and the binding constant for MPA–BSA complex are ~1 and 4.6 × 10³ M^?1 at 310 K, respectively. However, it can be concluded that the binding process of MPA with BSA is spontaneous and the main interaction forces between MPA and BSA are van der Waals force and hydrogen bonding interaction due to the negative values of ΔG⁰, ΔH⁰ and ΔS⁰ in the binding process of MPA with BSA. MPA prefers binding on the hydrophobic cavity in subdomain IIIA (site II′′) of BSA resulting in a slight change in the conformation of BSA, but BSA retaining the α‐helix structure. Copyright © 2016 John Wiley & Sons, Ltd.     

Density functional theory molecular modelling,DNA interactions,antioxidant, antimicrobial,anticancer and biothermodynamic studies of bioactive water soluble mixed ligand complexes

A novel series of bioactive water soluble mixed ligand complexes (1–5) [M^II(L)(phen)AcO]. nH₂O {where M?=?Cu (1) n?=?2; Co (2), Mn (3), Ni (4), n?=?4 and Zn (5) n?=?2} were synthesized from 2-(2-Morpholinoethylimino) methyl)phenol Schiff base ligand (LH), 1, 10-phenanthroline and metal(II) acetate salt in a 1:1:1 stoichiometric ratio and characterized by several spectral techniques. The obtained analytical and spectral data suggest the octahedral geometry around the central metal ion. Density functional theory calculations have been further supportive to explore the optimized structure and chemical reactivity of these complexes from their frontier molecular orbitals. Gel electrophoresis result indicates that complex (1) manifested an excellent DNA cleavage property than others. The observed binding constants with free energy changes by electronic absorption technique and DNA binding affinity values by viscosity measurements for all compounds were found in the following order (1)?>?(2)?>?(4)?>?(5)?>?(3) > (LH). The binding results and thermodynamic parameters are described the intercalation mode. In vitro antioxidant properties disclose that complex (1) divulges high scavenging activity against DPPH^?, ^?OH, O₂^?? NO^?, and Fe³⁺. The antimicrobial reports illustrate that the complexes (1–5) were exhibited well defined inhibitory effect than ligand (LH) against the selected different pathogenic species. The observed percentage growth inhibition against A549, HepG2, MCF-7, and NHDF cell lines suggest that complex (1) has exhibited superior anticancer potency than others. Thus, the complex (1) may contribute as potential anticancer agent due to its unique interaction mode with DNA.GRAPHICAL ABSTRACT

Communicated by Ramaswamy H. Sarma     

Combined spectroscopies and molecular docking approach to characterizing the binding interaction of enalapril with bovine serum albumin

The binding interaction between bovine serum albumin (BSA) and enalapril (ENPL) at the imitated physiological conditions (pH = 7.4) was investigated using UV–vis absorption spectroscopy (UV–vis), fluorescence emission spectroscopy (FES), synchronous fluorescence spectroscopy (SFS), Fourier transform infrared spectroscopy (FT‐IR), circular dichroism (CD) and molecular docking methods. It can be deduced from the experimental results from the steady‐state fluorescence spectroscopic titration that the intrinsic BSA fluorescence quenching mechanism induced by ENPL is static quenching, based on the decrease in the BSA quenching constants in the presence of ENPL with increase in temperature and BSA quenching rates >10¹⁰ L mol^?1 sec^?1. This result indicates that the ENPL–BSA complex is formed through an intermolecular interaction of ENPL with BSA. The main bonding forces for interaction of BSA and ENPL are van der Waal's forces and hydrogen bonding interaction based on negative values of Gibbs free energy change (ΔG ⁰), enthalpic change (ΔH ⁰) and entropic change (ΔS ⁰). The binding of ENPL with BSA is an enthalpy‐driven process due to |ΔH °| > |T ΔS °| in the binding process. The results of competitive binding experiments and molecular docking confirm that ENPL binds in BSA sub‐domain IIA (site I) and results in a slight change in BSA conformation, but BSA still retains its α‐helical secondary structure.     

Electronic and fluorescent studies on the interaction of DNA and BSA with a new ternary praseodymium complex containing 2,9-dimethyl 1,10-phenanthroline and antibacterial activities testing

In this study, fluorescence emission spectra, UV–vis absorption spectra, ethidium bromide (EB)-competition experiment, and iodide quenching experiment were used for the interaction study of the Fish salmon DNA (FS-DNA) with [Pr(dmp)2Cl3(OH2)] where dmp is 2,9-dimethyl 1,10-phenanthroline. The binding constant and the number of binding sites of the complex with FS-DNA were 6.09?±?0.04 M^?1 and 1.18, respectively. The free energy, enthalpy, and entropy changes (ΔG°, ΔH°, and ΔS°) in the binding process of the Pr(III) complex with FS-DNA were –8.02?kcal mol^?1, +39.44?kcal mol^?1, and +159.56?cal mol^?1 K^?1, respectively. Based on these results, the interaction process between FS-DNA with [Pr(dmp)2Cl3(OH2)] was spontaneous and the main binding interaction force was groove binding mode. Also, Fluorescence and electronic absorption spectroscopy were used in order to evaluate the binding characteristics, stoichiometry, and interaction mode of praseodymium(III) (Pr(III)) complex with bovine serum albumin (BSA). Title complex showed good binding propensity to BSA presenting moderately high Kb values. The fluorescence quenching of BSA by Pr(III) complex has been observed to be the static process. The positive ΔH° and ΔS° values showed that the hydrophobic interaction is the main force in the binding of Pr(III) complex and BSA. Eventually, the average aggregation number, <J>, of BSA potentially induced by title complex confirmed the 1:1 stoichiometry for title complex-BSA adducts. In vitro, antimicrobial activity of title complex was indicated that the complex is more active against both Escherichia coli and Enterococcus faecalis bacterial strains than Staphylococcus aureus, and Pseudomonas aeruginosa.

Communicated by Ramaswamy H. Sarma