Imtiyaz Ahmad Bhat

Bio-physicochemical analysis of ethylene oxide-linked diester-functionalized green cationic gemini surfactants

A novel series of oxy-diester-functionalized gemini surfactants (Cm-E2O-Cm) was synthesized and the physicochemical parameters were evaluated by surface tension and steady-state fluorescence measurements. Negative values of Gibbs free energy change of adsorption and micellization indicate that adsorption and micellization of Cm-E2O-Cm gemini surfactants are spontaneous. These surfactants have lower Krafft points and thus better solubility. Besides, they exhibit excellent foam and micro-emulsion stability. Interestingly, these geminis show low cytotoxicity, as revealed by HC50 analysis. FT-IR spectra after alkaline treatment confirm their cleavable nature. Moreover, a fascinating feature of these geminis is their considerably high biodegradability. Thus, a comprehensive study of the synthesized gemini surfactants has been carried out that may be significant for potential applications in various fields, more specifically in biomedicine and cosmetics, where efficiency and safety are strictly connected.

Conformational alterations induced by novel green 16-E2-16 gemini surfactant in xanthine oxidase: Biophysical insights from tensiometry, spectroscopy, microscopy and molecular modeling

Herein we report the interaction of a biodegradable gemini surfactant, ethane-1,2-diyl bis(N,N-dimethyl-N-hexadecylammoniumacetoxy) dichloride (16-E2-16) with bovine milk xanthine oxidase (XO), employing tensiometry, fluorescence spectroscopy, UV spectroscopy, far-UV circular dichroism spectroscopy (CD), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and computational molecular modeling. Surface tension results depict substantial changes in the micellar as well as interfacial parameters (CMC, ΠCMC, γCMC, Γmax, Amin, ΔGmic° and ΔGads°) of 16-E2-16 gemini surfactant upon XO combination, deciphering the interaction of XO with the gemini surfactant. Fluorescence measurements reveal that 16-E2-16 gemini surfactant causes quenching in the xanthine oxidase (XO) fluorescence spectra via static procedure and the values of various evaluated binding parameters (KSV, Kb, kq, ΔGb° and n) describe that 16-E2-16 effectively binds to XO. Three dimensional fluorescence, 8-anilino-1-naphthalene sulfonic acid (ANS) binding, F1F3 ratio, UV, CD, FTIR, SEM and TEM results delineate changes in the secondary structure of xanthine oxidase. Molecular docking results provide complement to the steady-state fluorescence findings and support the view that quenching occurs due to non-polar environment experienced by aromatic residues of the enzyme. The results of this study can help scientists to tune the conformation of an enzyme (XO) with biocompatible amphiphilic microstructures, which will help to unfold further understanding in the treatment modes of various diseases like gout, hyperuricemia, liver and brain necrosis.

Self-Aggregation of Surfactant Ethane-1,2-diyl bis(N,N-dimethyl-N-hexadecylammoniumacetoxy) Dichloride: Tensiometric, Microscopic, and Spectroscopic Studies

We have investigated the effect of salt additives (NaCl, Na₂SO₄, Na₃PO₄, NaTos, and NaAn) on the aggregation behavior of a cleavable biodegradable ester-bonded dicationic gemini surfactant, ethane-1,2-diyl bis(N,N-dimethyl-N-hexadecylammoniumacetoxy) dichloride (16-E2-16). A multitechnique approach employing tensiometry, fluorescence, proton magnetic resonance (¹H NMR), transmission electron microscopy (TEM), absorption spectrophotometry (UV), and Fourier transform infrared spectroscopy (FTIR) was utilized to probe physicochemical fluctuations. Appreciable changes were observed in various physicochemical parameters, viz., critical micelle concentration (CMC), surface excess concentration (Γ(max)), minimum area per headgroup (A(min)), free energy of micellization (ΔG(mic)°), free energy of adsorption (ΔG(ads)°), and aggregation number (N(agg)). Counter ions were found to affect through electrostatic and hydrophobic influence obeying the overall trend as NaAn > NaTos > Na₃PO₄ > Na₂SO₄ > NaCl. ¹H NMR, TEM, UV, and FTIR results reveal microstructure evolution and phase transitions. These results thus provide deeper insights in understanding of self-aggregation and microstructure evolution of biocompatible (green) aqueous systems of the gemini surfactant and their implications in the biomedical and pharmaceutical world, which could be helpful to improve their bioavailability and other biochemical aspects like drug delivery and gene transfection.

Interaction of a green ester-bonded gemini surfactant with xanthine oxidase: Biophysical perspective.

A multi technique approach was utilized to explore the interaction between a novel green gemini surfactant, ethane-1,2-diyl bis(N,N-dimethyl-N-tetradecylammoniumacetoxy) dichloride (14-E2-14), with bovine milk xanthine oxidase (XO). Tensiometric, spectroscopic, microscopic and molecular modeling results demonstrate significant interaction and structural change of native xanthine oxidase upon 14-E2-14 combination. The results obtained in this study may be beneficial for scientists to calibrate conformation of the enzyme by novel biodegradable/green microstructures; consequently, it would likely add new impetus in understanding the treatment modes of various diseases like gout, hyperuricemia, liver and brain necrosis. Moreover, the 14-E2-14-XO interaction assists to unfurl new routes in the designing/selection of green-surfactant-protein mixtures widely used in food processing, cosmetics, and pharmaceutical industries.

Anti-fibrillation propensity of a flavonoid baicalein against the fibrils of hen egg white lysozyme: potential therapeutics for lysozyme amyloidosis.

More than 20 human diseases involve the fibrillation of a specific protein/peptide which forms pathological deposits at various sites. Hereditary lysozyme amyloidosis is a systemic disorder which mostly affects liver, spleen and kidney. This conformational disorder is featured by lysozyme fibril formation. In vivo lysozyme fibrillation was simulated under in vitro conditions using a strong denaturant GdHCl at 3 M concentration. Sharp decline in the ANS fluorescence intensity compared to the partially unfolded states, almost 20-fold increase in ThT fluorescence intensity, increase in absorbance at 450 nm suggesting turbidity, negative ellipticity peak in the far-UVCD at 217 nm, red shift of 50 nm compared to the native state in Congo red assay and appearance of a network of long rope-like fibrils in transmission electron microscope (TEM) analysis suggested HEWL fibrillation. Anti-fibrillation potency of baicalein against the preformed fibrils of HEWL was investigated following ThT assay in which there was a dose-dependent decrease in ThT fluorescence intensity compared to the fibrillar state of HEWL with the maximum effect observed at 150-μM baicalein concentration, loss of negative ellipticity peak in the far-UVCD region, dip in the Rayleigh scattering intensity and absorbance at 350 and 450 nm, respectively, together with a reduction in the density of fibrillar structure in TEM imaging. Thus, it could be suggested that baicalein could prove to be a positive therapeutics for hereditary human lysozyme amyloidosis. Graphical abstract

New insights into binding interaction of novel ester-functionalized m-E2-m gemini surfactants with lysozyme: a detailed multidimensional study

In this article fluorescence spectroscopy, UV-visible spectroscopy, circular dichroism (CD), isothermal titration calorimetry (ITC), transmission electron microscopy (TEM) and molecular docking methods have been used to examine the interaction between dicationic ester-bonded gemini surfactants (m-E2-m) and hen egg white lysozyme (HEWL). The fluorescence and UV-visible absorption spectral measurements indicate m-E2-m–HEWL complex formation via static procedure. Binding isotherms reveal mainly cooperative binding of m-E2-m surfactants to HEWL. Circular dichroism, and pyrene fluorescence depict conformational changes in HEWL upon m-E2-m combination. Synchronous fluorescence shows that addition of m-E2-m has a remarkable effect on the micropolarity of aromatic residues (Tyr/Trp) of HEWL. Far-UV CD spectra demonstrate that the α-helical network of HEWL is disrupted and its content decreases from 30.68% to 20.83%/20.40%, respectively, upon 12-E2-12/14-E2-14 combination. ITC confirms the endothermicity of m-E2-m–HEWL interactions while slight exothermicity was observed in the 14-E2-14–HEWL system at higher molar ratios of surfactant. TEM micrographs reveal structural change in HEWL upon m-E2-m addition. Molecular docking illustrates that 14-E2-14 binds principally near to predominant fluorophores of lysozyme viz. Trp-108 and Trp-62 while 12-E2-12 binds in proximity of Trp-123. This study provides an important insight, particularly the contribution of Trp-123 in the fluorescence besides already known predominant fluorophores, Trp-62 and Trp-108. Moreover, this study would be significant in context of protein–surfactant interactions in terms of special m-E2-m molecular structure, which is essential in determining their future use as excipients in pharmaceutical/drug delivery related compilations.

Unraveling the interaction of hemoglobin with a biocompatible and cleavable oxy-diester-functionalized gemini surfactant

Surfactant-protein mixtures have attracted considerable research interest in recent years at the interface of chemical biology and medicinal chemistry. Herein, the interaction between a green gemini surfactant (C16-E2O-C16) and a redox protein hemoglobin was examined through a series of in vitro experimental techniques with an attempt to provide a comprehensive knowledge of the surfactant-protein binding interactions. Quantitative appraisal of the fluorescence/CV data showed that the binding of C16-E2O-C16 to Hb leads to the formation of thermodynamically favorable non-covalent adduct with 1:1 stoichiometry. UV-vis spectra demonstrated that the effect of C16-E2O-C16 on Hb is highly concentration dependent. Far-UV and near-UV CD spectra together elucidated the formation of molten globule state of Hb upon C16-E2O-C16 addition. Temperature dependent CD explicated the effect of C16-E2O-C16 on the thermal stability of Hb. Furthermore, the structural investigation of Hb via pyrene/synchronous/three-dimensional fluorescence and FT-IR spectroscopy provided the complementary information related to its microenvironmental and conformational changes. Computational studies delineated that C16-E2O-C16 binds in the vicinity of β-37 Trp at the α1β2 interface of Hb. Overall, this study is expected to clarify the binding mechanism between Hb/other congeners and surfactant at the molecular level that are known to have immense potential in biomedical and industrial areas.

Synthesis, molecular docking and evaluation of antifungal activity of Ni(II), Co(II) and Cu(II) complexes of porphyrin core macromolecular ligand.

Porphyrin core dendrimeric ligand (L) was synthesized by Rothemund synthetic route in which p-hydroxy benzaldehyde and pyrrole were fused together. The prepared ligand was complexed with Ni(II), Cu(II) and Co(II) ions, separately. Both the ligand and its complexes were characterized by elemental analysis and spectroscopic studies (FT-IR, UV-Vis, (1)HNMR). Square planar geometries were proposed for Cu(II), Ni(II) and Co(II) ions in cobalt, Nickel and copper complexes, respectively on the basis of UV-Vis spectroscopic data. The ligand and its complex were screened on Candida albicans (ATCC 10231), Aspergillus fumigatus (ATCC 1022), Trichophyton mentagrophytes (ATCC 9533) and Pencillium marneffei by determining MICs and inhibition zones. The activity of the ligand and its complexes was found to be in the order: CuL ˃ CoL ≈ NiL ˃ L. Detection of DNA damage at the level of the individual eukaryotic cell was observed by commet assay. Molecular docking technique was used to understand the ligand-DNA interactions. From docking experiment, we conclude that copper complex interacts more strongly than rest two.

Biophysical perspective of the binding of ester-functionalized gemini surfactants with catalase.

Interaction of surfactants with biomacromolecules is an essential subject of biophysical chemistry to address their diverse applications in industry, biomedical, and cosmetic domains. In this context, we have examined the binding interactions of three ester-functionalized surfactants (m-E2-m) with bovine liver catalase (BLC, 10μM) by employing a multi-technique approach. The m-E2-m geminis quench fluorescence intensity of BLC through static procedure. The binding ability of concerned gemini surfactants was found to be in the order 12-E2-12 (Kb=2.3×10(2))>16-E2-16 (Kb=1.1×10(2))>14-E2-14 (Kb=1.0×10(2)). Quenching efficacy, as determined by Ksv values, were observed as 12-E2-12 (3.0×10(2))>16-E2-16 (1.4×10(2))>14-E2-14 (1.0×10(2)). The negative ΔG°b values (12-E2-12 (-13.48kJ/mol)>16-E2-16 (-11.65kJ/mol)>14-E2-14 (-11.41kJ/mol)) indicate spontaneous nature of m-E2-m-BLC interactions. UV-vis spectroscopy, circular dichroism (CD) and micropolarity (F1/F3) assessments indicate conformational changes in BLC upon m-E2-m combination. ITC confirms the stability of BLC upon gemini combination. Docking provides support to fluorescence results by presenting the localization site of m-E2-m surfactants near to aromatic residues (mainly Tyr, Trp and Phe). Moreover, since surfactant-protein interactions have essential miscellaneous implications, therefore, this study can be significant for industrial and biomedical realms.

In vitro disintegration of goat brain cystatin fibrils using conventional and gemini surfactants: Putative therapeutic intervention in amyloidoses.

Many protein misfolding diseases in mammalian system are characterised by the accumulation of protein aggregates in amyloid fibrillar forms. Several therapeutic approaches include reduction in the production of the amyloidogenic form of proteins, increase in the clearance rate of misfolded or aggregated proteins, and direct inhibition of the self-assembly process have been explained. One of the possible remedial treatments for such disorders may be to identify molecules which are capable of either preventing formation of fibrils or disintegrating the formed fibrils. In this work, we have studied the effect of conventional surfactants; sodium dodecylsulphate (SDS), cetyl trimethylammonium bromide (CTAB) and dicationic gemini (16-4-16) surfactant on the disintegration of the goat brain cystatin (GBC) fibrils above their critical micelle concentrations (CMC) using ThT fluorescence, CD, TEM, Congo red and turbidity approaches. The results obtained are significant and showing the best disintegrating potency on GBC fibrils with gemini surfactant. The outcome from this work will aid in the development and/or design of potential inhibitory agents against amyloid deposits associated with amyloid diseases.