Samita Basu

Magnetic Field Effect Corroborated with Docking Study to Explore Photoinduced Electron Transfer in Drug-Protein Interaction

Conventional spectroscopic tools such as absorption, fluorescence, and circular dichroism spectroscopy used in the study of photoinduced drug-protein interactions can yield useful information about ground-state and excited-state phenomena. However, photoinduced electron transfer (PET) may be a possible phenomenon in the drug-protein interaction, which may go unnoticed if only conventional spectroscopic observations are taken into account. Laser flash photolysis coupled with an external magnetic field can be utilized to confirm the occurrence of PET and authenticate the spin states of the radicals/radical ions formed. In the study of interaction of the model protein human serum albumin (HSA) with acridine derivatives, acridine yellow (AY) and proflavin (PF(+)), conventional spectroscopic tools along with docking study have been used to decipher the binding mechanism, and laser flash photolysis technique with an associated magnetic field (MF) has been used to explore PET. The results of fluorescence study indicate that fluorescence resonance energy transfer takes place from the protein to the acridine-based drugs. Docking study unveils the crucial role of Ser 232 residue of HSA in explaining the differential behavior of the two drugs towards the model protein. Laser flash photolysis experiments help to identify the radicals/radical ions formed in the due course of PET (PF(•), AY(•-), TrpH(•+), Trp(•)), and the application of an external MF has been used to characterize their initial spin-state. Owing to its distance dependence, MF effect gives an idea about the proximity of the radicals/radical ions during interaction in the system and also helps to elucidate the reaction mechanisms. A prominent MF effect is observed in homogeneous buffer medium owing to the pseudoconfinement of the radicals/radical ions provided by the complex structure of the protein.

Characterization of the triplet charge-transfer state of 4-amino- N -methylphthalimide in aprotic and protic media by laser flash photolysis

The intermediate charge-transfer (CT) transients of 4-amino-N-methylphthalimide (4-AMP) have been attempted to be characterized mainly by laser flash photolysis and other steady-state and time-resolved fluorescence studies. Previously, the singlet intramolecular-charge-transfer (ICT) states have been investigated for various phthalimides using fluorescence techniques. This is probably the first attempt to identify the triplet state of CT transients of 4-AMP by laser flash photolysis studies. The various photophysical parameters have been estimated in different aprotic, protic and heterogeneous media to differentiate the types of CT character in the different media. In aprotic solvents ICT predominates but in protic media the formation of a twisted intramolecular-charge-transfer (TICT) state from the ICT state is facilitated owing to reduction of the torsional barrier. Hence, in polar protic solvents some of the non-radiative deactivation channels, especially internal conversion (IC) from the excited singlet state to the ground state, become effective, which reduces the fluorescence quantum yield and lifetime of the singlet ICT species. Moreover, in protic and micellar media, formation of semiquinone radical takes place through hydrogen abstraction from the media by triplet 4-AMP as further confirmed by application of an external magnetic field.

Time-resolved studies of the effect of a magnetic field on exciplex luminescence

Time-resolved studies of the magnetic field effect on pyrene-dimethylaniline exciplex luminescence in non-alcoholic solvent mixtures (dielectric constant of 16) have been performed with the help of a time-correlated single-photon counting technique. The shape of the time-variation curve is interpreted in terms of a simple analytical model.

Interactions of guanine and guanosine hydrates with quinones: a laser flash photolysis and magnetic field effect study.

Laser flash photolysis and an external magnetic field have been used to study the interaction of two quinone molecules, namely, 9,10-anthraquinone (AQ) and 2-methyl 1,4-naphthoquinone, commonly known as menadione (MQ), with one of the DNA bases, guanine (G) and its nucleoside guanosine hydrate (dG). In organic homogeneous medium, it has been observed that G undergoes a predominant hydrogen (H) abstraction reaction with both the quinones while dG supports photoinduced electron transfer (PET) along with H abstraction. On the other hand, in SDS medium, G supports PET with AQ but not with MQ. However, behavior of dG remains unperturbed toward AQ and MQ with the change in medium. All of these observations have been explained on the basis of stabilization of radical ion pair and difference in size of the quinones, which can affect the distance of approach among the interacting molecules.

Magnetic field effect on exciplex luminescence in liquids

Abstract The effect of a magnetic field on the luminescence of unlinked as well as linked exciplex systems has been discussed. The magnetic field modulated luminescence. (Δφ/φ) is not only dictated by the hyperfine interaction in the radical ion pair, but also by the environment, such as viscosity and dielectric constant (ϵ) of the medium and presence of other molecules in the neighbourhood of the exciplex. A complex interplay between spin evolution, radical pair recombination and diffusion determine the magnitude and nature of the magnetic field effect (MFE). The dependence of (Δφ/φ) on the ϵ could be explained on the basis of simple theoretical models. The concept of Heisenberg spin exchange has been invoked to rationalise the quenching of MFE by lanthanide ions. Time-resolved studies provide useful information regarding the dynamics of the spin-evolution of the system. In viscous medium the rotational diffusion slows down and the MFE becomes dependent on the direction of the field with respect to the exciplex.

Use of zirconium phosphate as ion exchanger in some parent-daughter radioisotope separations

Zirconium phosphate as ion exchanger suitable for column operation has been prepared by mixing hot metaphosphoric acid solution with a solution of zirconium oxychloride when the white insoluble phosphate separated out which was dried and purified. The ratio of zirconium: phosphate was found to be 1:2. Separation of parent-daughter systems like115Cd-115mIn,144Ce-144Pr and210Pb-210Bi were carried out with this exchanger. γ-ray spectrum of the separated115mIn and the β-decay curve of144Pr and210Bi showed that all the daughter activities are radiochemically pure. The separation process in each case takes less than half an hour and the yield is quantitative.

Potency of photoinduced electron transfer and antioxidant efficacy of pyrrole and pyridine based Cu(II)-Schiff complexes while binding with CT-DNA

Here we report a systematic and comparative study to define a correlation between the structure and function of a series of simple, biologically active small inorganic Schiff base copper complexes for the occurrence of charge transfer phenomenon in calf thymus DNA (CT-DNA) using transient absorption spectroscopy corroborated with magnetic field effect. Four copper(II) Schiff base complexes with differently substituted heterocyclic ligands with antioxidant activity have been used. The binding constants of the order of ∼ 10(4) support the moderate binding affinity of the complexes towards CT-DNA. The methyl-substituted pyrrole complex shows maximum binding affinity (Kb: 8.33 × 10(4)) compared to others. The occurrence of photoinduced electron transfer (PET) from CT-DNA to pyrrole containing complexes has been confirmed by identifying the corresponding transient radical ions whereas the extent of PET with pyridine substituted complexes is too small to be observed. The increase of the yield of radical ions in presence of magnetic field depicts that the initial spin correlation in geminate radical ion pair is triplet. The difference between experimental and calculated B½ values, the measure of hyperfine interactions (HFI) present in the system, arises due to hole hopping through intrastrand and interstrand DNA bases. The unsubstituted pyrrole complexes cleave DNA much more than the methyl-substituted one. Therefore, the probability of intrastrand superexchange increases with methyl-substituted complexes, that reduces the rate of hole hopping and hence the B½ value.

Simultaneous occurrence of energy transfer and photoinduced electron transfer in interactions of hen egg white lysozyme with 4-nitroquinoline-1-oxide.

The carcinogenic drug 4‐nitroquinoline‐1‐oxide (4NQO) has been found to bind with the protein hen egg white lysozyme as evident from fluorescence quenching experiments. The binding constant and stoichiometry have been determined. The values of the thermodynamic parameters indicate that the interaction is an enthalpy‐driven spontaneous phenomenon. The experimental value of change in free energy is similar to that obtained from the docking study. The far UV circular dichroism spectra show some changes in the secondary structure of protein. The high value of bimolecular quenching constant leads to the possibility of Förster resonance energy transfer (FRET). Along with FRET, the photoinduced electron transfer (PET) from tryptophan residue of protein to 4NQO has also been evident from the transient absorption spectra obtained in laser flash photolysis experiments. The simultaneous occurrence of FRET and PET is the key factor for quenching of intrinsic fluorescence of the protein as it binds with the drug.

Laser flash photolysis studies and magnetic field effect on a new heteroexcimer between N-ethylcarbazole and 1,4-dicyanobenzene in homogeneous and heterogeneous media

The electron transfer (ET) process between a fluorophore (N-ethylcarbazole) and a quencher (1,4-dicyanobenzene) has been studied by absorption, steady-state and time-resolved fluorescence and laser flash photolysis techniques in homogeneous and micellar media. The effect of a magnetic field on the ET process of this system has also been carried out by flash photolysis. The results reflect the following unique features of this system. The reduction potentials of the acceptor and the donor are such that the exciplex formation is possible by ET, moreover, as the charge separation is small a weak exciplex is formed even in a highly polar solvent, e.g. acetonitrile (MeCN). Thus, the exciplex formation and solvent-separated ion pair (SSIP) formation in MeCN take place simultaneously. The experimentally obtained bimolecular quenching constant, kq, from the Stern–Volmer plot, agrees satisfactorily with theoretically calculated kq for an ET reaction applying Marcus theory. The exciplex formation inside the micellar medium enables us to study the magnetic field effect (MFE) on this exciplex system. The simultaneous occurrence of the exciplex and radical ion pair in MeCN as well as the formation of the exciplex within the micellar environment, most probably for the first time, ensure a special characteristic of this exciplex system. Another novel feature is the abnormal behaviour of this system in benzene, which has also been discussed here.

Effect of variation of dielectric constant on the magnetic field modulation of exciplex luminescence: Nontypical behavior of alcohols

The effect of variation of dielectric constant (e) on the relative magnetic field effect on singlet luminescence (Δφ/φ) has been studied using a typical exciplex system at a saturating field. The study indicates strong specificity in the perturbation of the magnetic field effect by alcoholic solvents. In constrast to alcohols where relative singlet magnetic field effect is of the order of 1% only, the magnetic field effect in non‐alcoholic medium reaches as high as 4.5%. Moreover, e variation in alcohols yields curves which are distinctly different from those in nonalcoholic media.