Pal, Samanwita

Analysis of the interaction of pesticides and their metabolites with the cellular proteins has drawn considerable attention in past several years to understand the effect of pesticides on environment and mankind. In this study, we have investigated the binding interaction of Bovine Serum Albumin (BSA) with a widely used organophosphorous insecticide chlorpyrifos (CPF), and its stable metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) to provide a comparative analysis of the two molecules by employing various spectroscopic techniques viz., UV–vis absorption, Circular Dichroism (CD), and Fluorescence spectroscopy. The fluorescence quenching studies of BSA emission in two different solvents viz., water and methanol in presence of CPF and TCPy have led to the revelation of several interesting facts about the pesticide-protein interaction. It has been found that both the molecules cause static quenching of BSA emission as seen from the Stern-Volmer constant (Ksv) irrespective of the solvent used for the analysis. While TCPy is a stronger quencher in water, it exhibits comparable quenching capacity with CPF in methanol. The solvent dependent differential binding interaction of the two molecules finally indicates possibility of diverse bio-distribution of the pesticides within human body. The UV–vis and CD spectra of BSA in presence of the test molecules have unravelled that the molecules formed ground state complex that are highly reversible in nature and have minimal effect on the protein secondary structure. Furthermore it is also understood that structural changes of BSA in presence of CPF is significantly higher compared to that in presence of TCPY.

The present study aims to investigate the motional dynamics of risperidone within polylactic co-glycolic acid (PLGA) microsphere by employing solution state 1H and 19F nuclear magnetic resonance (NMR) measurements. Risperidone, a second-generation fluorinated antipsychotic drug used for the treatment of schizophrenia is commercially marketed as PLGA microsphere formulation resulting in prolonged release of the drug in solution. Although the current trend in the pharmaceutical market is to develop drug formulation with long-acting release (LAR) products, complete physicochemical characterization of such formulations are scarce. Especially the effects of microsphere encapsulation on the motional properties and diffusion behavior of the drugs are not discussed adequately in any of the earlier reports. We therefore, have employed NMR relaxation and diffusion measurements to decipher the interaction of PLGA cavity water with risperidone. A detailed analysis of NMR relaxation rates confirmed the event of encapsulation and the presence of local motion in the non-fluorinated end of risperidone. Further, the relaxation data indicated a significant alteration in 19F chemical shift anisotropy (CSA) and CSA/dipole-dipole (DD) cross-correlated relaxation mechanism and decreased effect of solvent relaxation pointing out reduced water concentration within the microsphere cavity. 1H and 19F diffusion coefficients of risperidone led to the information about hydrodynamic radius of risperidone in free and encapsulated states. Measurement of hydrodynamic radius supported the presence of limited water in PLGA cavity allowing higher translational mobility of risperidone after the encapsulation.

Emeraldine Hydrochloride salt is coated on copper substrate and studied for hydrogen storage and hydrogen evolution reaction in 1 M NaOH. Phenomenological thermodynamic approach demonstrated elsewhere in conjunction with the cyclic voltammetry data is employed to calculate the solvent modified work function for polyaniline coated copper in alkaline medium as −0.65 eV. The solvated work function is in satisfactory agreement with the band gap difference of π−π* transition in emeraldine base and π- polaron transition in emeraldine salt ca −0.6 eV as reported in the literature. 13C and 1H NMR studies revealed that polyaniline undergoes switching between emeraldine salt and emeraldine base, before and after hydrogen evolution respectively. The volume of hydrogen evolved on polyaniline coated copper is 1.64 times than that on copper as demonstrated by Gas chromatography. Thus emeraldine salt, when stored in NaOH act as hydrogen storage medium and upon electrochemical perturbation can release hydrogen at controlled rate depending on the scan rate employed.

In this report, our main focus is to introduce a set of one-dimensional (1D) NMR methods based on chemical shift, relaxation, and magnetization transfer, namely, NOE and chemical exchange involving selective pulse excitation to study the solution dynamics of drug in free and encapsulated state within polymeric microsphere. In this regard 5-fluorouracil (5-FU) loaded poly lactic-co-glycolic acid (PLGA) microspheres are prepared as model system via standard water-in-oil-in-water emulsification method. One-dimensional 1H and 19F nuclear magnetic resonance (NMR) spectra of 5-FU in presence of PLGA microspheres presented a significant change in linewidth and relaxation rates compared with free 5-FU confirming encapsulation. Furthermore, loss of coupling pattern in 1H and 19F NMR of PLGA encapsulated 5-FU as compared with free 5-FU suggests an enhanced –NH and –H2O protons exchange dynamics in the interior of the microsphere indicating hydrated microsphere cavity. Quantification of exchange dynamics in case of free and PLGA-encapsulated 5-FU was attempted employing 1D selective NOESY and 1D multiply selective inversion recovery experiments. Analysis of the exchange rates confirmed existence of more than one kind of water population within the cavity as mentioned in an earlier solid state NMR report.

The present study aims to characterize the molecular interaction and photo-degradation behaviour of halogen (–F and –Cl) containing novel insecticide, flupyradifurone, (FPD) in the presence of humic acid (KHA), isolated from Karwar, western Rajasthan, India. Time-dependent photo-degradation kinetics of UV-exposed FPD is quantified in the absence and presence of KHA employing one dimensional 1H and 19F solution-state NMR. The pseudo first-order photo-degradation rate constant quantified for FPD showed a significant decrease in the presence of KHA. Interestingly, variable degradation rates are found from 1H and 19F NMR spectral changes indicating chemical moiety wise degradation of FPD. Further, NMR saturation transfer difference (STD), relaxation, and diffusion experiments have been employed for the complete evaluation of binding interactions of KHA with FPD and its major degradation product difluoroacetic acid (DFA). STD experiments revealed that FPD binds to KHA through the chlorinated pyridine ring while the –F containing moiety of FPD does not show any detectable interaction. Relevant kinetic parameters, namely association constants and Gibbs free energy of interaction are quantified at neutral pH conditions by diffusion experiments depicting a stronger and more spontaneous association of FPD with KHA (KA = 55.55 M−1) compared to that of DFA-KHA (KA = 10.90 M−1). Both FPD and DFA bind with KHA through weak non-covalent interaction indicating the encapsulation of these molecules within KHA hindering the photo-degradation process of FPD. Concomitantly, it is also envisaged that FPD will be more persistent in soil compared to DFA that may leach out to groundwater.

In Vitro analysis of the interaction of organophosphate pesticides (OP) with bovine serum albumin (BSA) is crucial to understand their potential effects at the molecular level. In this context, we have employed Saturation Transfer Difference (STD) NMR experiments in conjunction with molecular docking studies to unravel the binding interaction of the OP chlorpyrifos (CPF), diazinon (DZN) and parathion (PA) in solution. The relative STD (%) suggested the detailed epitope mapping of these OP with BSA while the concentration-dependent STD NMR studies were performed to obtain the complex dissociation constant (KD) of the OP-BSA complexes; KD=1.81×10−4 M, 1.30×10−3 M and 1.11×10−3 M for CPF, DZN and PA were extracted respectively. Similar binding modes were identified for all the three OP using STD site-marker experiment. ITC experiments were performed as a complementary method that revealed a high binding affinity of OP-BSA complexes through non-covalent interaction. Molecular docking confirmed the possible interacting chemical groups of OP-BSA complexes. These significant results furnish valuable information about the toxicity risk of OP to proteins. Communicated by Ramaswamy H. Sarma.

The present study aims to establish a simple approach involving multi-field multinuclear longitudinal relaxation (R1) analysis of the solvents to decipher solute-solvent interactions during the solvation of model carbohydrates in aqueous trifluoroethanol (TFE) co-solvent systems (TFE:D2O). The behavior of D2O and TFE is monitored around β-CD (β-cyclodextrin) and glucose throughR1D(2H) andR1F(19F), respectively. Correlation times (τc) are estimated for D2O and TFE for various % (v/v) compositions of TFE:D2O mixtures. The differential trends of theR1orτcratio for D2O and TFE (in the presence and absence of carbohydrates) revealed that both β-CD and glucose undergo selective solvation by TFE in comparison to D2O. Owing to its encapsulation properties, β-CD exhibited a comparatively higher tendency to undergo solvation by TFE than glucose. The maximum transfer of solute bound water to bulk solvent appears in the 20-30% (v/v) TFE range. The current approach emerges as being straightforward in contrast to traditional methods that primarily focus on solute behavior to unravel the preferential solvation dynamics.

The present study aims at the development and characterization of zinc oxide (ZnO) nanoparticles as a carrier for various anti-cancerous drugs viz. 5-Fluorouracil (5-FU), Doxorubicin (DOX) and Daunorubicin (DNR). ZnO nanoparticles were prepared by standard precipitation method. The measurement of optical band gap using UV-Visible Diffuse Reflectance Spectroscopy (DRS) analysis reveals the lowering of ZnO band gap after the drug loading. Crystallite size of free and drug loaded ZnO nanoparticles were determined using X-ray Diffraction (XRD) analysis. The crystallite size of ZnO nanoparticles increases after the drug loading. Both the techniques confirm the adsorption of drug molecules on ZnO surface.

A well-defined controlled selective edge functionalization of graphene oxide (GO) is of high interest because it allows tuning the chemical and physical properties of graphene oxide with minimal damage to the carbon at the basal plane. The present work reports a rapid one-step synthesis of edge fluorinated graphene oxide (FGO) from GO in an aqueous medium. A selective fluorination of the tertiary carbon at the edge of GO was achieved by chemoselective substitution of the carboxylic acid with fluorine in one hour following a decarboxylative fluorination technique using 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (SELECTFLUOR) and silver ion catalyst. The structure and composition of FGO were characterized by multiple analytical techniques, such as TEM, SEM, XRD, EDS, FTIR, XPS, Raman spectroscopy, etc. As observed in XPS and NMR analysis, the decarboxylative fluorination of GO resulted in the formation of covalent C–F bonds at the edge. The absence of the peak associated with the C–F group on the basal plane in 19F NMR clearly indicates the fluorination at the edge of GO. Most importantly, similar linewidth and spectral patterns in proton-decoupled 19F{1H} and proton-coupled 19F NMR spectra of FGO suggest that the fluorine atoms are bonded to the tertiary carbon atom. The selective functionalization of the tertiary carbon at the edges of GO achieved here, is unprecedented. The fluorine group at the edge of GO can act as a new reaction center for subsequent chemical modification. This simple edge-controlled fabrication method described here provides a facile pathway to fabricate multifunctional GO and expand their potential applications. Graphical abstract: [Figure not available: see fulltext.].

The present study aims to comprehend the adsorption behavior of a set of anticancer drugs namely 5-fluorouracil (5-FU), doxorubicin and daunorubicin on ZnO nanoparticles (ZnO NPs) proposed as drug delivery systems employing solid state (ss) NMR, FTIR and Cyclic Voltammetry (CV) analysis. FTIR and 1H MAS ssNMR data recorded for bare ZnO nanoparticle confirmed the presence of adsorbed –OH groups on the surface. 13C CP-MAS NMR spectra recorded for free and ZnO surface adsorbed drug samples exhibited considerable line broadening and chemical shift changes that complemented our earlier report on UV-DRS and XRD data of surface adsorption in case of 5-FU. Moreover, a remarkable enhancement of 13C signal intensity in case of loaded 5-FU was observed. This clearly indicated rigid nature of the drug on the surface allowing efficient transfer of 1H polarization from the hetero nitrogen of 5-FU to ZnO to form surface hydroxyl (–OH) groups and the same has been observed in the quantum chemical calculations. To further analyze the motional dynamics of the surface adsorbed 5-FU, longitudinal relaxation times (T1) were quantified employing Torchia method that revealed significant enhancement of 13C relaxation rate of adsorbed 5-FU. The enhanced rate suggested an effective role of quadrupolar contribution from 67Zn to the 13C relaxation mechanism of ZnO_5-FU. The heterogeneous rate constant (khet), average free energy of activation (∆G≠) and point of zero charge (PZC) measured for free and drug loaded ZnO NPs samples using CV further support the SS-NMR results.