Munna Sarkar

A library of IR bands of nucleic acids in solution.

This review presents a compilation and discussion of infrared (IR) bands characteristic of nucleic acids in various conformations. The entire spectral range 1800-800 cm(-1) relevant for DNA/RNA in aqueous solution has been subdivided into four sections. Each section contains descriptions of bands appearing from group specific parts of nucleic acid structure, such as nucleobase, base-sugar, sugar-phosphate and sugar moiety. The approach allows comparisons of information obtained from one spectral region with another. The IR band library should facilitate detailed and unambiguous assignment of structural changes, ligand binding, etc. in nucleic acids from IR spectra. is aimed at highlighting specific features that are useful for following major changes in nucleic acid structures. also concerns some recent results, where IR spectroscopy has been used to obtain semi-quantitative information on coexisting modes of sugar pucker in oligonucleotides.

Influence of different micellar environments on the excited-state proton-transfer luminescence of 3-hydroxyflavone

Abstract Excited-state proton-transfer and dual emission behaviour of 3-hydroxyflavone (3HF) have been investigated in representative micellar media. The relative yield of the green tautomer emission of 3HF shows pronounced enhancement in micelles, which suggests that the 3HF molecules are largely distributed in regions of low polarity, where external hydrogen-bonding perturbations are minimized. Further, the usefulness of the tautomer emission yield as a sensitive probe for estimation of critical micelle concentration values, is demonstrated. Preliminary results of studies on emission decay kinetics are also reported.

Spectroscopic studies of microenvironment dictated structural forms of piroxicam and meloxicam

Long acting non-steroidal anti-inflammatory drugs (NSAIDs) belonging to the oxicam group have attracted special interest because of their diverse biological functions. In this study we present the influence of microenvironment on the spectral properties of two oxicam drugs viz. piroxicam and meloxicam. For the two drugs, a high energy shift of the UV absorption maxima was observed with increasing drug concentrations both in protic solvent like ethanol and aprotic solvent like dimethyl sulfoxide (DMSO). Studies involving variation of percentage volume of water as well as pH, using absorption and steady state fluorescence spectroscopy, allow us to identify the principal species present at different concentrations of the drugs. It is found that even trace quantity of water present in the solvent becomes significant at low concentration of the drug making the water/drug ratio sufficiently large to support the formation of anion. As the concentration of the drug increases, the number of water molecules available per drug molecule decreases and most of the drug molecules face a relatively apolar environment in which zwitterionic/neutral species become predominant. This results in a concentration-dependent high-energy shift of the absorption maximum. This study demonstrates how microenvironments of these drugs guide the nature of the predominant form present in solution.

Membrane Fusion Induced by Small Molecules and Ions

Membrane fusion is a key event in many biological processes. These processes are controlled by various fusogenic agents of which proteins and peptides from the principal group. The fusion process is characterized by three major steps, namely, inter membrane contact, lipid mixing forming the intermediate step, pore opening and finally mixing of inner contents of the cells/vesicles. These steps are governed by energy barriers, which need to be overcome to complete fusion. Structural reorganization of big molecules like proteins/peptides, supplies the required driving force to overcome the energy barrier of the different intermediate steps. Small molecules/ions do not share this advantage. Hence fusion induced by small molecules/ions is expected to be different from that induced by proteins/peptides. Although several reviews exist on membrane fusion, no recent review is devoted solely to small moleculs/ions induced membrane fusion. Here we intend to present, how a variety of small molecules/ions act as independent fusogens. The detailed mechanism of some are well understood but for many it is still an unanswered question. Clearer understanding of how a particular small molecule can control fusion will open up a vista to use these moleucles instead of proteins/peptides to induce fusion both in vivo and in vitro fusion processes.

Incorporation of NSAIDs in micelles: implication of structural switchover in drug–membrane interaction

Non-steroidal anti-inflammatory drugs (NSAIDs) of oxicam group are not only effective as anti-inflammatory agents but also show diverse functions. Their principal targets are cyclooxygenases, which are membrane-associated enzymes. To bind with the targets these drugs have to pass through the membrane and hence their interactions with biomembranes should play a major role in guiding their interactions with cyclooxygenases. Here we have studied the interactions of three NSAIDs of oxicam group viz. piroxicam, meloxicam and tenoxicam with micelles having different headgroup charges, as simple membrane mimetic systems. Spectroscopic methods have been used to understand the interaction of these drugs with Cetyl N,N,N-trimethyl ammonium bromide (cationic), Sodium dodecyl sulphonate (anionic) and Triton X-100 (neutral) micelles. Our results demonstrate that the environment of the drugs i.e. the nature of the micelles plays a decisive role in choosing a specific prototropic form of the drugs for incorporation. Additionally it induces a switch over or change between different prototropic forms of piroxicam, which is correlated with the change in their reactivities in presence of different surface charges, given by the change in pK(a) values. These results together, indicate that in vivo, the diverse nature of biomembranes might play a significant role in choosing the particular form of oxicam NSAIDs that would be presented to their targets.

Effect of reverse micelles on the intramolecular excited state proton transfer (ESPT) and dual luminescence behaviour of 3-hydroxyflavone

Abstract The excited-state proton transfer and dual emission behaviour of 3-hydroxyflavone (3HF) have been investigated in reverse micelles of sodium bis(2-ethylhexyl) sulphosuccinate (AOT)/ n -heptane at different values of water to surfactant molar ratio ( W O ). The green tautomet emission (λ max ≈ 524 nm) and blue-violet normal emission (λ max ≈ 400 nm) originate from two different ground state populations of 3HF molecules, which are located respectively in the apolar phase and at the interphase of the reverse micelles, proximal to the AOT head groups. With increasing W 0 the relative yield of the green emission band is enhanced with a concomitant decrease in that of the blue-violet emission. This is interpreted in terms of the population of 3HF molecules which are initially located in the interfacial region proximal to the polar head groups being “pushed” out into the apolar phase, where external hydrogen bonding perturbations are minimized.

Photophysical studies of oxicam group of NSAIDs: piroxicam, meloxicam and tenoxicam

Oxicam group of non steroidal anti-inflammatory drugs has been chosen as a prototype molecular group that shows diverse biological functions and dynamic structural features. Photophysical studies of three drugs from this group viz., piroxicam, meloxicam and tenoxicam have been carried out in different solvents with varying polarity, H-bond character and viscosity. The spectral responses of different prototropic forms of these drugs towards varying solvent parameters have been studied, with the aim to characterize their interaction in biomimetic environment non-invasively. The nature of the lowest transition has been identified. The extinction coefficient, quantum yield and viscosity dependence on the nature of the solvents, all indicate the extreme sensitivity of these drugs to their microenvironment.

Membrane fusion: a new function of non steroidal anti-inflammatory drugs.

Membrane fusion is an important event in many biological processes and is characterized by several intermediate steps of which content mixing between the two fusing vesicles signals the completion of the process. Fusion induced solely by small drug molecules is not a common event. Non Steroidal Anti-Inflammatory Drugs (NSAIDs), that control pain and inflammation, are also capable of exhibiting diverse functions. In this study we present a new function of NSAIDs belonging to the oxicam group, as membrane fusogenic agents. Small Unilamellar Vesicles (SUVs) formed by the phospholipid, dimyristoylphosphatidylcholine (DMPC), were used as model membranes. Fluorescence assays using terbium/dipicolinic acid (Tb/DPA) were used to monitor content mixing and corresponding leakage in presence of the drugs. Transmission Electron Microscope (TEM) was also used to image fusion bodies in drug treated vesicles as compared to the untreated ones. The results show that the three oxicam NSAIDs viz. Meloxicam, Piroxicam and Tenoxicam can induce fusion of DMPC vesicles and lead the fusion process to completion at a very low drug to lipid ratio (D/L) of 0.045. The oxicam drugs exhibit differential fusogenic behavior as reflected in the kinetics of content mixing and leakage, both of which can be described by a single exponential rate equation. Moreover, not all NSAIDs can induce membrane fusion. Indomethacin, an acetic acid group NSAID and ibuprofen, a propionic acid group NSAID, did not induce fusion of vesicles. This new property of NSAIDs has important applications in biochemical processes.

Luminescence behaviour of 7-hydroxyflavone: temperature-dependent effects

Abstract On excitation at 365 nm, 7-hydroxyflavone (7HF) emits a blue fluorescence (λmax ≈ 450 nm) in ethanol—methanol (1:1 by volume ) glass at 77 K. This fluorescence shifts to longer wavelengths, leading to a green emission (λmax ≈ 537 nm) at room temperature (298 K). The blue and green fluorescence is due to selective excitation of the same ground state species, namely the conjugate anion of 7HF (7HFA), which is present at low concentration in neutral alcohol solution. A large change in the excited state dipole moment of 7HFA compared with the ground state takes place; this has been calculated to be 13.7 ± 1 D using the solvatochromic shift method. The large blue shift of the steady state emission maximum on lowering the temperature from 289 to 77 K is rationalized in terms of solvent relaxation around the excited fluorophore.

Luminescence behaviour of 7-hydroxyflavone in aerosol OT reverse micelles: excited-state proton transfer and red-edge excitation effects

Abstract The fluorescence emission properties of 7-hydroxyflavone (7HF) are examined in reverse micelles of aerosol-OT (AOT) in n -heptane. Excited-state proton transfer (ESPT) leading to dual-emission behaviour ( λ max ≈ 396–417 nm and 545–550 nm which can be assigned to the normal and ESPT tautomer emission respectively) as well as red edge excitation shift (REES) of the normal fluorescence band are observed. Upon gradual addition of water to the 7HF-AOT- n -heptane solution, conspicuous enhancement of the ESPT tautomer emission intensity takes place together with a progressive red shift of the normal emission, that continues up to ([H 2 O]/[AOT]) = W 0 ≈ 8–10, beyond which no significant changes occur. Interestingly, with increasing value of W 0 , the changes observed in the magnitude of the REES effect, Δλ (Δ λ is the difference in λ max of the normal fluorescence as λ exc is shifted from midband ( λ = 310 nm) to red edge ( λ = 350 nm) of the absorption band) parallel to changes in the λ max of normal emission, as well as that of the relative intensity I T l N of the tautomer vs. normal emission bands. Even at high W 0 (e.g. W 0 = 36), these parameters do not reach the limiting values found in bulk water, indicating that 7HF is predominantly localized near the head groups of AOT, mostly in the bound water phase.