Interaction of acridinedione dye with a globular protein in the presence of site selective and site specific binding drugs: Photophysical techniques assisted by molecular docking methods.

Photophysical investigations and molecular docking studies of photoinduced electron transfer (PET) based fluorophores of acridine family with a globular protein, Bovine Serum Albumin (BSA) bound to non-narcotic drugs like phenylbutazone (PB) and flufenamic acid (FA) were carried out in aqueous solution. PB and FA are site specific and site selective drugs, wherein PB predominantly binds at the site (I) whereas FA selectively orients towards site (II) of BSA. Acridinedione (AD) dyes, both resorcinol and dimedone based are hydrophobic in nature and exhibits a combination of both hydrophobic and hydrogen-bonding interactions that are based on the binding sites in BSA. The extent of displacement of AD from the binding sites of BSA by PB and FA are elucidated and established from variation in the fluorescence lifetime and relative amplitude distribution of free and dye bound in site (I) and site (II). The extent of binding affinity of PB-BSA and FA-BSA in the presence of AD is minimal when compared to other site I and II drugs. This is attributed to AD dye bound to several amino acid residues present in BSA such that the dye prefers multiple binding sites in BSA even in the presence of FA and PB. Further, the dye bound to several amino acid residues of BSA ascertains the combination of hydrogen-bonding, hydrophobic interactions, pi-pi and pi-alkyl interaction apart from the binding through sites (I) and (II) from molecular docking methods. The combination of fluorescence tools with molecular modelling techniques provides an excellent approach in determining the stability of these complexes containing competitive guest molecules in the presence of a fluorescence probe and the binding characteristics of dye in a micro heterogeneous environment.

Fluorescence and quantum mechanical approach on the interaction of amides and their role on the stability and coexistence of the rotamer conformations of L-tryptophan in aqueous solution.

Photophysical investigation on the fluorescence decay characteristics of L-tryptophan and a derivative N-acetyl-L-tryptophanamide (NATA) with alkyl amides were carried out in water. L-tryptophan exists in the zwitterionic form and exhibits a biexponential lifetime which is correlated to the existence of rotamer structures. Addition of formamide (F) and dimethylformamide (DMF) results in a decrease in the fluorescence lifetime and its proportion of the most stable structure of L-tryptophan wherein acetamide (ACM) results in an increase of the same. Interestingly, all the amides result in the formation of the lifetime of the rotamer whose lifetime doesn't exist initially and the lifetime and its distribution increases irrespective of the nature of amide. The interaction between L-tryptophan and amide is attributed to hydrogen-bonding such that these interactions influence the relative proportion of the existence of individual rotamers in the presence of amides.Strikingly, in the case of NATA that does not exhibit rotamer structures; the fluorescence lifetime is quenched in the presence of F, whereas ACM and DMF result in a larger fold of enhancement resulting in two different lifetimes. The variation in the fluorescence lifetime and amplitude of the various conformers of L-tryptophan and of NATA is completely governed by the concentration of the amides in solution such that the microenvironment surrounding the fluorophores are completely reorganised. The hydrogen-bonding functional groups in amides that are responsible for the coexistence of rotamers are elucidated and well supported by quantum mechanical (QM) studies. Time-correlated single-photon counting(TCSPC) technique is used as a probe as well as marker in establishing the variation in the lifetime properties of L-tryptophan and NATA with non-fluorescent hydrogen-bonding solutes in water which promotes this as fascinating field of research in the context of fluorescence properties of a complicated amino acid-like tryptophan.

Photophysical and Electrochemical Studies of 4-Dicyanomethylene 2,6-Dimethyl-4H-Pyran (DDP) Dye with Amides in Water.

Photophysical and electrochemical studies of DDP dye with Formamide and alkyl substituted amides were carried out in water. Addition of Formamide (F), Acetamide (ACM), N,N-Dimethylformamide (DMF), Dimethylacetamide (DMAC) to DDP dye result in an isosbestic point. A fluorescence enhancement of DDP dye is observed on the addition of amides. Apart from the fluorescence enhancement, the addition of formamide result in no significant shift in the position of emission maxima of DDP dye whereas addition of ACM and DMF result in a shift towards the blue and red region respectively. DDP dye exhibits three lifetime components which are unique in lifetime and amplitude. The fluorescence lifetime and relative amplitude of DDP dye varies significantly by addition of amides in aqueous solution which are influenced by amidewater hydrogen-bonding network and hydrophobic influences of the alkyl substituted amides. The nature of interaction between dye and amide be predominantly through hydrogen-bonding wherein the carbonyl oxygen (C=O) of amides are bonded to N-H hydrogen of DDP dye through water molecule. The existence of more than one microenvironment of DDP dye in aqueous phase is elucidated by Electrochemical Impedence Spectroscopy (EIS) through Nyquist plots wherein it signifies that there exist at least three different micro environments which support the existence of different fluorescence lifetimes. Fluorescence spectral technique is used as an efficient tool to elucidate the nature of interaction of water soluble probe with hydrogen-bonding solutes is established in our studies.

Pd-Catalyzed C-H arylation of pyridazine-based fused 1,2,4-triazoles: overriding selectivity at the usual position by undermining of preferred chelate formation.

The applicability of C-H functionalization to medicinally important 2-pyridyl-based N-heterocycles suffers from severe challenges owing to the high Lewis basicity of the N-atom. This arrests catalytic activity and yields undesirable positional selectivity due to preferential chelate formation. In this regard, we report a novel palladium(ii)-catalyzed arylation strategy on multiple-N-containing pyridazines by over-riding the functionalization due to a chelated palladacycle. We report a regioselective mono-arylation at the 8-position of diphenyl azolopyridazines without any ortho-C-H activation on the proximal phenyl groups. This methodology presents a broad arylation scope with uncompromised yield and positional selectivity, including the heteroarylation of N-heterocycles, which is an unprecedented feat for these types of molecules.

Expedient synthesis of new cinnoline diones by Ru-catalyzed regioselective unexpected deoxygenation-oxidative annulation of propargyl alcohols with phthalazinones and pyridazinones.

Ruthenium-catalyzed simple, cascade and one-pot synthesis of cinnoline-fused diones has been carried out by the C-H activation of phthalazinones/pyridazinones accomplished by the unusual deoxygenation of propargyl alcohols. The bond selectivity is accredited to the traceless directing nature of the hydroxyl group of propargyl alcohol. A sequential C-H activation, insertion and deoxy-oxidative annulation has been proposed based on the preliminary mechanistic study.