Bovine Serum Albumin Binding Research Articles

Novel 1,2,4-triazoles as anti-enzymatic agents: Microwave versus conventional synthesis, characterization, docking and BSA binding studies

In the drug development process, 1,2,4-triazoles have become widely acknowledged as an effective structural motif. Through both classical and microwave supported approaches, analogues based on 1,2,4-triazole were synthesized, and they have the potential to act as strong anti-enzymatic agents. Starting from 4‑methoxy benzensulfonyl chloride (1), subsequent carboxylate (3), carbohydrazide (4), 1,2,4-triazole (5) and their hybrids,7a-j, were successfully synthesized in attractive yields. All the synthesized analogs were characterized by 1H NMR, 13CNMR and IR spectral data. The enzymes acetyl cholinesterase (AChE), butyryl cholinesterase (BChE), and lipoxygenase (LOX), which are in charge of a variety of problems in people's daily lives, were considered in the biological assessment. Compounds,7g(IC50 (µM)=3.15±0.13) and 7h(IC50 (µM)=3.48±0.11) were outstanding against AChE while compounds, 7g(IC50 (µM)=39.17±0.29) and 7j(IC50 (µM)=35.42±0.41)against BChE comparative to Eserine(IC50 (µM)=0.19±0.05, 0.62±0.08)used as a standard respectively against both enzymes respectively. Inhibition potential against LOX was found excellent by compounds 7a(IC50 (µM)=12.53±0.25) and 7j(IC50 (µM)=19.28±0.46) among all the tested compoundsrelative to Quercetin(IC50 (µM)=2.34±0.35) used as a standard. The molecular docking and BSA (bovine serum albumin) binding studies further supported the physiologically active anti-enzymatic behaviors of synthesized compounds and they could be the future anti-enzymatic drugs after further assessments.

Effect of fatty acids and pH on the binding of BSA to silica and polystyrene.

Bovine serum albumin (BSA) is a frequently used blocking agent for in-vitro diagnostic (IVD) applications. Fatty acid stabilized (FAS) and fatty acid free (FAF) BSA are the common grades of BSA commercially offered for blocking. It is known that both fatty acid presence and pH influence the conformation of BSA. Previous adsorption studies have examined the effect of fatty acids or pH on BSA blocking, but little data is available for how these factors together impact function. In this study, we used Quartz Crystal Microbalance with Dissipation (QCM-D) to further understand of how pH and fatty acids impact BSA adsorption to IVD relevant surfaces.

Acidic pH impact on BSA domains I & II adsorption to a silica dioxide surface.

Bovine Serum Albumin (BSA) is a protein used as a passive blocker, adsorbing to various surfaces to reduce nonspecific interactions. BSA contains three structurally homologous domains but comprised of a different number of basic/acidic amino acids, causing each domain to respond to pH changes differently. At neutral pH, domain I contains many negatively charged residues producing a total net charge of −17. At pH 5.2, these residues become protonated, shifting the net charge to +1. The change in pH alters the charge of BSA and therefore may affect protein-surface interactions. Silica is a common surface used in bead-based immunoassays. Experimental observations suggest that adsorption occurs when both BSA and silica are negatively charged but the mechanism is not fully understood. By using theoretical techniques like molecular dynamics (MD) simulations we can analyze this protein-surface interaction and begin to understand it on a molecular level. In this study, we investigated how the change in pH can impact the adsorption of BSA to silica using MD simulations. BSA binding to silica at pH 5.2 and pH 7.0 were compared by performing simulations using NAMD. We observed that at pH 5.2, domains I and II orient closer to the surface to create many intermolecular interactions, while at pH 7.0 only domain II interacted with the silica surface. This interaction could be due to the change in surface charge of domain I at pH 7.0 and pH 5.2. At pH 7.0 domain I is highly negatively charged impacting the electrostatic interactions that are observed at pH 5.2, where domain I is less negatively charged. With MD simulations, we found pH impacts protein-surface interaction and can affect the mechanism of protein adsorption.

Carboxy‐thioether‐thiolato titanium–graphene oxide nanocomposite as drug delivery system for targeted cancer therapy: Design, characterization, bovine serum albumin binding study, and biological evaluation

Carboxy‐thioether‐thiolato Ti (IV) complex (TiCTT) and its graphene oxide nanocomposite (GO–TiCTT) were prepared and characterized for the development of novel compounds with enhanced antibacterial and anticancer capabilities, and the loading ratio of TiCTT was found to be approximately 33.3%. Thermal studies and zeta potential revealed that GO–TiCTT is more stable than GO, whereas SEM and TEM revealed efficient TiCTT adsorption on the surface of GO. Various biophysical procedures were used to investigate the interactions of CTT, TiCTT, GO, and GO–TiCTT nanocomposite with bovine serum albumin (BSA). The results revealed that the intrinsic fluorescence quenching of BSA resulting from low concentrations was caused by the formation of stable BSA adducts via the binding interaction with BSA. The stable adduct had a stoichiometry of 1:1 and binding constants (Kb) in the order of 105 M1 at 310 K for CTT, TiCTT, and GO–TiCTT, indicating a very strong binding interaction with BSA. Based on the sign and magnitude of the free energy change (G#), it can be concluded that the binding process with BSA was spontaneous, with van der Waals force and hydrogen bonding interaction as the main interaction forces. A combined quenching process was observed at higher concentrations of these compounds. Using the stopped‐flow technique, the TiCTT release behavior from the nanocomposite was investigated, and the GO–TiCTT system demonstrated pH‐responsive and sustained drug release. Furthermore, when compared to GO, CTT, TiCTT, and GO–TiCTT nanocomposite demonstrated good antibacterial activity against both Gram‐positive and Gram‐negative bacteria. They also have higher cytotoxicity against HepG2 human liver cancer cells than CTT. The calculated BSA‐binding constants matched the antimicrobial and cytotoxic results well. As a result, this research could lead to the development of a drug delivery system.

Preliminary investigation on biological possessions of Saquinavir‐modified quinoline‐derived azadipeptidomimetics

AbstractHerein, azadipeptidomimetic molecules were designed and synthesized using a quinoline‐histidine‐amino acid sequence with terminal amino acid modification. In‐silico studies were carried out to evaluate the compound's HIV protease‐1 inhibition temperament. In‐vitro anti‐proliferative possessions of the test compounds were studied by executing a series of experiments, namely DNA binding, bovine serum albumin (BSA) binding capability, and cytotoxicity assay on MCF‐7 cells. The molecule 5j exhibited remarkable results in all experiments; it has an excellent DNA binding constant (3.76 × 105), higher serum albumin unbound concentration of 5.96%, and a significant antiproliferative effect on MCF‐7 cells with IC50 value 0.31 nM.

GAS CHROMATOGRAPHY-MASS SPECTROMETRY PROFILING, ANTI-INFLAMMATORY EVALUATION, AND MOLECULAR DOCKING STUDIES OF ESSENTIAL OIL AND SCENTED EXTRACT FROM THE Porana volubilis Burm. f. FLOWER

Volatile components of Porana volubilis Burm. f. flowers from Bangkok were extracted by using steam distillation and solvent extraction prior to analysis by gas chromatography-mass spectrometry (GC-MS) and their antiinflammatory activity was assessed in vitro and in silico. Forty-two compounds were identified with essential oil. The key volatile components were detected in the hexane-scented extract. Twenty-one compounds were detected with major volatile components of octacosanaol, dodecanoic acid, nonacosane, n-hexadecanoic acid, and tetratriacontane for ethanolic scented extract. The essential oil and extract were evaluated for their in vitro anti-inflammatory effect by protein denaturation assay. The essential oil showed the most potent anti-denaturation activity with IC50 values of 537.6 g/mL. The primary components of essential oil were submitted ta molecular docking research based on their anti-inflammatory effect. The obtained results revealed that the main components were found as the crucial interactions for binding in the bovine serum albumin (BSA) binding site. The results obtained demonstrated the essential oil of P. volubilis is the potential source for the anti-inflammatory agent.

Mononuclear discrete Ag(I) complexes of aryl substituted (E)-N-phenyl-1-(pyridin-3-yl)methanimine: In vitro biological activities and interactions with biomolecules

The synthesis of three pyridinyl imines (L1-L3) with electron-donating and electron-withdrawing functional groups, as well as their silver(I) complexes (1a-3a, 1b-3b and 1c-3c), resulted from our ongoing search for novel metallodrugs with potential pharmacological activity. Various analytical and spectroscopic analyses were used to characterize the Ag(I) complexes. The single crystal X-ray diffraction analysis of complexes 3a and 3b in the solid state confirmed their linear geometry around the Ag(I) center. In vitro antibacterial properties of the complexes evaluated using the minimum inhibitory concentration (MIC) method revealed that complexes containing either a Me- or an F-substituent exhibited greater activity. The ferric-reducing antioxidant power (FRAP) experiment revealed that complexes with hydroxyl substituents have high antioxidant potential. These complexes with IC50 values ranging from 0.86 to 2.47 mg mL-1 outperformed ascorbic acid, with an IC50 of 2.68 mg mL-1. The reported complexes bound to CT-DNA via intercalation mode with significant binding constants for complexes whose ligands bore the OH- substituent. Bovine serum albumin (BSA) binding affinity to the complexes ranges from moderate to high. The studied complexes with methyl substituents are promising anti-cervical cancer candidates.

Synthesis, crystal studies, antimicrobial activity, and BSA binding studies of metal complexes derived from pyridyl-based hydrazone: Multi-spectroscopic and DFT approach

We describe herein the synthesis of a pyridyl-benzothiazole hydrazone ligand (BP) and its metal complexes (BP1–BP4) incorporating Co(II), Ni(II), Cu(II), and Zn(II) cations. The molecular structures of BP and two of its complexes, BP1 and BP3, have been determined by single-crystal X-ray diffraction analysis. Octahedral complexation of the central metal ion by the NNN donor ligand in a 1:2 stoichiometry has been confirmed by various spectroscopic techniques, that is, IR spectroscopy, NMR spectrometry, and UV/Vis spectrophotometry, and corroborated by electrospray-ionization mass spectrometry and cyclic voltammetry. Diffuse-reflectance spectra revealed the presence of d-d transitions in all of the complexes, except in the case of BP4, which has no unpaired electron. The thermal stabilities of the complexes have been assessed by thermogravimetry and differential thermogravimetry, which revealed stepwise decomposition. Significant differences in the morphologies of the complexes have been discerned by FE-SEM analysis. Hirshfeld surface analysis has revealed the establishment of N⋅⋅⋅H, H⋅⋅⋅H, and C⋅⋅⋅H noncovalent interactions. Density functional theory (DFT)-based calculations have been applied to investigate the chemical reactivities and optimized structures of BP and BP1–BP4. A 1,3-proton shift in BP was confirmed and the HOMO-LUMO energy gap was assessed through DFT-based methods. Photophysical studies have revealed a large Stokes shift for BP, which is reduced upon complexation with metal ions. In vitro anti-microbial screening of the prepared compounds has been performed against four bacterial strains (Bacillus cereus, Staphylococcus aureus, Escherichia coli, and Xanthomonas campestris) and two fungal strains (Candida albicans and Fusarium oxysporum), which revealed most potent inhibition of bacterial and fungal growth, with minimum inhibitory concentrations of 128 and 256 μg/mL, by BP1 and BP3, respectively. BP1 exhibits broad-spectrum anti-bacterial activity exceeding that of the standard drug chloramphenicol. Spectroscopic methods have been utilized to explore the interaction between BP1 and bovine serum albumin (BSA). A hypsochromic shift in fluorescence intensity and a hyperchromic shift in the absorption band of BSA with different concentrations of BP1 have yielded significant binding information. BSA binding studies have revealed a negative value of Gibbs free energy, confirming the spontaneity of BSA–BP1 complex formation.

Electroanalysis of Ibuprofen and Its Interaction with Bovine Serum Albumin.

The current work presents a sensitive, selective, cost-effective, and environmentally benign protocol for the detection of ibuprofen (IBP) by an electrochemical probe made of a glassy carbon electrode modified with Ag-ZnO and MWCNTs. Under optimized conditions, the designed sensing platform was found to sense IBP up to a 28 nM limit of detection. The interaction of IBP with bovine serum albumin (BSA) was investigated by differential pulse voltammetry. IBP-BSA binding parameters such as the binding constant and the stoichiometry of complexation were calculated. The results revealed that IBP and BSA form a single strong complex with a binding constant value of 8.7 × 1013. To the best of our knowledge, this is the first example that reports not only IBP detection but also its BSA complexation.

Protein interactions, molecular docking, antimicrobial and antifungal studies of terpyridine ligands

Resistance to antibiotics/antibacterials/antifungals in pathogenic microbes has been developing over the past few decades and has recently become a commonplace public-health peril. Thus, alternative nontoxic potent antibiotic agents are covertly needed to control antibiotic-resistant outbreaks. In an effort to combat the challenges posed by the co-occurrence of multidrug resistance, two terpyridine ligands 4′-(4-N,N′-dimethylaminophenyl)-2,2′:6′,2″-terpyridine (L1) and 4′-(4-tolyl)-2,2′:6′,2″-terpyridine (L2) have been designed, prepared and confirmed their structure by spectral studies. Thereafter, antimicrobial assay was performed against gram positive and negative bacterial strains along with fungal strains. Both compounds L1 and L2 exhibited remarkable inhibitory activities against bacteria, Escherichia coli and Staphylococcus aureus at MIC values 6.25 and 3.125 µg/ml, respectively. In addition, in silico molecular docking studies were ascertained with bacterial DNA gyrase and fungal demethylase. Furthermore, both L1 and L2 could bind Bovine Serum Albumin (BSA) protein and binding interaction has been studied with the help of UV-Visible and fluorescence spectroscopy. While fluorescence of BSA unperturbed in the presence of L2, an addition of L1 to the solution of BSA resulted significant quenching. The binding constant calculations at different temperature confirmed that the fluorescence quenching between BSA and L1 is predominantly static in nature. The toxicity of L1 and L2 was checked using Drosophila melanogaster. The toxicity analysis suggest both the dyes are non-cytotoxic in nature. Communicated by Ramaswamy H. Sarma

Spectroscopic studies on binding of ibuprofen and drotaverine with bovine serum albumin

The interaction between ibuprofen (analgesic) and drotaverine (smooth muscle relaxant) drugs with bovine serum albumin (BSA) was investigated using both experimental (UV–Vis, fluorescence, and circular dichroism spectroscopy) and theoretical (molecular mechanics) methods. Both drugs quench the intrinsic fluorescence of BSA through static processes. The binding constant of the BSA–drotaverine complex is found to be relatively higher than that of the BSA–ibuprofen complex. The binding distance between BSA and ibuprofen/drotaverine was calculated to be 1.7 and 3.1 nm, respectively. Both fluorescence and circular dichroism spectral studies confirmed conformational changes in the BSA upon binding with these drugs. From both displacement competition studies and molecular docking, it was found that drotaverine can displace ibuprofen at higher concentrations, but ibuprofen can bind to other sites on the BSA. Circular dichroism showed that drotaverine has a stabilizing effect on the secondary structure of BSA in the presence of ibuprofen, which on its own leads to an increase in the disordered fraction at high concentrations.These observations imply that concurrent administration of these two drugs can be effective as a combination therapy in the management of pain due to primary dysmenorrhea, even when the disease tends to gain resistance to the NSAIDs; their competition for the BSA binding sites should be taken into account.

Molecular spectroscopic and docking analysis of the interaction of fluorescent thiadicarbocyanine dye with biomolecule bovine serum albumin

Binding studies of the water-soluble thiadicarbocyanine dye 3,3’-diethylthiadicarbocyanine acetate (DTC) with bovine serum albumin (BSA) were examined under physiological conditions using spectroscopic techniques like fluorescence, UV-Visible, circular dichroism (CD), FT-IR and molecular docking methods. Compiled experimental results envisage that DTC quench the fluorescence intensity of BSA. The increasing binding constants (K) were found to be in the order of 103 Mol−1 as a function of temperature, as calculated from the fluorescence quenching data. The quenching mechanism, thermodynamic parameters (ΔH0, ΔS0 and ΔG0) and the number of binding sites have been explored. CD values showed that the secondary structure of the BSA has been altered upon binding to DTC. Displacement experiments were carried out with different site probes to find out the binding site of DTC on BSA and it was found that binding interaction at site II of sub-domain IIIA. The interference of common metal ions on the interaction of DTC with BSA has also been studied. The experimental data exhibit that DTC interacts with BSA by hydrophobic forces. The experimental findings from BSA binding studies were validated by using in silico molecular docking technique. The results of the investigations were accurately supported by studies on molecular docking. The optimal shape of the molecular probe demonstrated the affinity as a free binding energy release of −7.37 Kcal/mol. The present research report endeavors to the approachable nature of water-soluble DTC dye and paves way for targeted biological interactions. Communicated by Ramaswamy H. Sarma

Manipulating the distribution of surface charge of PEDOT toward zwitterion-like antifouling properties

Poly(3,4-ethylenedioxythiophene) (PEDOT) has been regarded as one of the most attractive conductive materials for making bioelectronics. Surface modification is one of the most important methods to enhance the performance of PEDOT-based bioelectronics. To investigate the surface charge effect on the behavior of protein binding on PEDOT, we develop a new positively charged functionalized EDOT monomer, EDOT-N+, to copolymerize with another negatively charged carboxylic acid-modified EDOT monomer, EDOT-COOH. The poly(EDOT-N+-co-EDOT-COOH) film is prepared by the electropolymerization method. By mixing the two monomers with different feed ratios, we can tune the distribution of surface charges. The actual composition of the copolymer is determined by toluidine blue O staining. Based on the result of TBO staining, a copolymer with a 1:1 ratio of EDOT-N+ to EDOT-COOH is obtained when the monomer solution of composition at [EDOT-N+]: [EDOT-COOH] = 8 : 2, which is due to a slower polymerization rate of EDOT-N+ compared to EDOT-COOH. To further testify the antifouling property of poly(EDOT-N+-co-EDOT-COOH), nonspecific protein binding of bovine serum albumin and lysozyme were measured in situ by using a quartz crystal microbalance. The results also show that at [EDOT-N+]: [EDOT-COOH] = 8 : 2, poly(EDOT-N+-co-EDOT-COOH) presented good antifouling property. Therefore, we propose a zwitterion-like antifouling property from the poly(EDOT-N+-co-EDOT-COOH) with an equal density of both positive and negative functional groups.

A magnetostrictive self-powered biosensor based on Au-BaTiO3-FeGa & PDMS

Piezoelectric flexible sensors have been used to detect biomolecules such as sweat and glucose because of their passive, simple structure and high sensitivity. This paper proposes a novel flexible piezoelectric Au-BaTiO3-FeGa & PDMS biosensor in which magnetostrictive deformation amplifies the surface stress generated by biomolecules combining on the thin film. The modification process of bovine serum albumin (BSA) binding with the sensor was initially determined by the first principles approach. Then, the sensing mechanism was verified by finite-element simulation. Based on the simulation results, flexible Au-BaTiO3-FeGa & PDMS biosensors were prepared, modified, and measured. The structure, modification, and detection of the sensors were analyzed by digital microscopy, Fourier transform infrared spectrometry (FTIR), atomic force microscopy (AFM), and scanning electron microscopy (SEM). The responses of the biosensors detecting different BSA solution concentrations under magnetic fields were then investigated. Experimental results indicate that the biosensor has the highest sensitivity under a magnetic field of 30 mT.

Interaction mechanism of benzophenone-type UV filters on bovine serum albumin: Insights from structure-affinity relationship

Benzophenone (BP)-type UV filters can cause structural changes of carrier protein in plasma. The binding process of five BP-type UV filters with bovine serum albumin (BSA) was investigated by multiple characterization methods, along with their structure-affinity relationship involving the structure of the five BP-type UV filters and their binding affinity for BSA. The BP-type UV filters investigated bound to BSA spontaneously, and altered conformation of BSA. The binding constants and number of binding sites between BP-type UV filters and BSA were 103–106 M−1 and 0.82–1.26, respectively. These BP-type UV filters and BSA interacted with the same binding forces and went through the similar binding process, suggesting that the benzophenone skeleton structure was primarily responsible for the BP-type UV filters and BSA binding, and changes in the structure of the BSA. The BP-type UV filters with hydroxyl substituent (BP-1 and BP-9) and non-polar molecules (BP-6) had a high affinity for binding BSA and had a greater impact on BSA conformation.

Antimicrobial and antibiofilm activities and bovine serum albumin binding properties of benzimidazolium derivative NHC salts and their Ag(I)‐NHC complexes

Benzimidazole type N‐heterocyclic carbene molecules and their metal complexes have well‐known biological activity. Elemental silver and silver complexes also have antibacterial and antifungal activity. In this study, silver complexes with 1‐allyl 5,6‐dimethylbenzimidazolium derivative ligands were analyzed for their antimicrobial and antibiofilm activities. Additionally, bovine serum albumin (BSA) binding properties of the molecules were analyzed by spectrophotometric methods, and the details of interactions of the molecules with BSA were investigated by molecular docking methods. While N‐heterocyclic carbene salts showed moderate antifungal and antibiofilm activity, silver complexes of these salts have strong antimicrobial activity with <1.9–15.6 μg/ml minimal inhibitory concentration (MIC) values. On the other hand, carbene salts have better affinity against BSA than the complexes. Additionally, the interaction of the optimized complexes with SarA and BSA were analyzed by molecular docking methods. According to in vitro and in silico evaluation, the studied Ag complexes may be utilized for advanced studies.

Lophine-cinnamoyl hybrids: Synthesis, photophysical properties and a spectroscopic and molecular dynamics approach towards interactions with bovine serum albumin

Lophine and cinnamic acid derivatives have gained considerable attention due their chemical, biological and fluorescence emission properties. Herein we reported the synthesis of a new family of lophine-cinnamoyl hybrids connected by a methylene chain with two to nine carbon atoms. The hybrids show absorption in the ultraviolet and emission in the blue-violet region independent of the length of the alkyl chain spacer. Non-covalent interactions of the hybrids to bovine serum albumin (BSA) were investigated by UV–Vis absorption and fluorescence spectroscopy. Overall, the hybrids display moderate affinities for BSA (binding constants in the range 10–14 × 104 M−1) and can be effectively employed as protein probes using BSA as a model. The theoretical calculations showed preferential interactions of the hybrids with the binding pocket located near to Trp213 and the number of binding sites equal to 1 are in agreement with the experimental data obtained through the Stern-Volmer approach.

A new heterotrimetallic sandwich‐like CuII–LaIII–CuII (3d–4f–3d) cluster as a model anticancer drug in interaction with FS‐DNA and BSA and as a new artificial catalyst for catecholase activity

A new heterotrimetallic sandwich‐like CuII–LaIII–CuII cluster, [(valpn)2Cu2La(NO3)2]NO3(H2O)1.8, (H2valpn = 1,3‐propanediylbis(2‐iminomethylene‐6‐methoxy‐phenol)), was synthesized by the reaction of [Cu(valpn)] with La (NO3)3.6H2O (1:1 M ratio) at room temperature. The resulted cluster was characterized by X‐ray diffraction, UV–Vis and IR spectroscopy, and elemental analysis (CHN). The crystal structure of the cluster revealed that La(III) ion was sandwiched between two [Cu(valpn)] moieties and located in the open compartments of two copper Schiff base complexes and being surrounded by 12 oxygen atoms. This cluster complex, as a model anticancer drug, was investigated in interaction with fish sperm deoxyribonucleic acid (FS‐DNA) using docking study and experimental methods such as fluorescence and UV–Vis spectroscopy, circular dichroism spectroscopy (CD), cyclic voltammetry (CV), viscosity measurements, and agarose gel electrophoresis. These investigations suggested intercalative interaction between the cluster complex and FS‐DNA. Plasma proteins are other targets for the anticancer drugs, so the cluster–bovine serum albumin (BSA) interaction was also investigated. For evaluating the binding, Stern–Volmer constants (KSV) and the number of binding sites (n) were calculated. It was proposed that the electrostatic interaction was the main force in the cluster–BSA binding. Cytotoxic activity was assayed by MTT assay toward LACaP, MCF‐7, and HeLa cancer cell lines. The IC50 values of the cluster for HeLa and LACaP cell lines were lower than for MCF‐7 cell lines. The docking studies were also performed for cluster–BSA and cluster–DNA interactions. The cluster was also investigated as an artificial enzyme in catechol oxidase activity, and kinetics of the oxidation of 3,5‐di‐tert‐butylcatechol catalyzed by the cluster was studied.

New ternary Fe(III)-8-hydroxyquinoline–reduced Schiff base complexes as selective anticancer drug candidates

Due to the growing prevalence of cancer diseases, new therapeutic options are urgently needed, and drugs based on metal ions other than platinum are alternatives with exciting possibilities. We report the synthesis, characterization and biological effect of mixed-ligand Fe(III)-aminophenolate complexes derived from salicylaldehyde and L-tryptophan with quinoline derivatives as co-ligands, namely 8-hydroxyquinoline (8HQ), [Fe(L)(8HQ)(H2O)] (1) and its 5-cloro derivative (Cl8HQ), [Fe(L)(Cl8HQ)(H2O)] (2). The complex bearing the aminophenolate and lacking the quinoline co-ligand, [Fe(L)(Cl)(H2O)2] (3), was prepared for comparison. The analytical and spectroscopic characterization revealed that 1 and 2 are octahedral Fe(III) complexes with the aminophenolate acting as a dianionic tridentate ligand and 8HQ co-ligands as bidentate chelates. Spectroscopic techniques and molecular docking studies were used to evaluate the ability of these complexes to bind bovine serum albumin (BSA) and calf thymus DNA. Complex 2 [Fe(L)(Cl8HQ)(H2O)] was the one showing higher affinity for both biomolecules. Cell viability was assessed in breast, colorectal and bone human cancer cell lines. 1 and 2 were found to be more active than cisplatin in all cell lines tested. A non-tumoral fibroblast line (L929, mouse non-tumoral fibroblasts) was used to evaluate selectivity. The results evidence that 2 shows much higher selectivity than 1 in all cell lines tested, but particularly in bone cancer cells in which selectivity index (SI) values are 8.0 and 18.8 for 1 and 2, respectively.

Unravelling the thermodynamics and binding interactions of bovine serum albumin (BSA) with thiazole based carbohydrazide: Multi-spectroscopic, DFT and molecular dynamics approach

In the present manuscript, a novel 2-((4-chlorophenyl)amino)-N'-(4-(diethylamino)-2-hydroxybenzylidene)thiazole-4-carbohydrazide (H1) has been synthesized and characterized using various spectroscopic techniques including 1D, 2D NMR, FT-IR and single-crystal XRD. Various electrostatic parameters such as frontier molecular orbital (FMO), natural bond orbital (NBO), Fukui functions and nonlinear optical (NLO) properties were explored by Density Functional Theory (DFT) using B3LYP/6-311+G(d,p) level of theory. The effect of solvent polarity on electronic absorption spectra was investigated using Time dependent-DFT. The thermodynamic parameters such as heat capacity, entropy and enthalpy were also investigated at different temperatures. Moreover, photophysical studies were performed to examine the effect of solvent polarity and viscosity. A positive solvatochromism and a 7 fold fluorescence enhancement were observed with the increase of solvent polarity and viscosity, respectively. The compound exhibit aggregation-induced emission in THF:H2O system. The binding interaction of H1 with BSA and its mechanism has been investigated using UV-visible absorption and fluorescence quenching techniques. The thermodynamics of binding suggest the presence of spontaneous hydrogen bonding interactions, as –ve values of ΔG, ΔS and ΔH were observed. The experimental results obtained from BSA binding studies were validated through in silico molecular docking and dynamics techniques. Molecular modelling studies perfectly corroborate the experimentally obtained results.