Design and Synthesis of Imidazole and Triazole Pyrazoles as Mycobacterium Tuberculosis CYP121A1 Inhibitors

The emergence of untreatable drug-resistant strains of Mycobacterium tuberculosis is a major public health problem worldwide, and the identification of new efficient treatments is urgently needed. Mycobacterium tuberculosis cytochrome P450 CYP121A1 is a promising drug target for the treatment of tuberculosis owing to its essential role in mycobacterial growth. Using a rational approach, which includes molecular modelling studies, three series of azole pyrazole derivatives were designed through two synthetic pathways. The synthesized compounds were biologically evaluated for their inhibitory activity towards M. tuberculosis and their protein binding affinity (K_D). Series 3 biarylpyrazole imidazole derivatives were the most effective with the isobutyl ( 10 f ) and tert-butyl ( 10 g ) compounds displaying optimal activity (MIC 1.562 μg/mL, K_D 0.22 μM ( 10 f ) and 4.81 μM ( 10 g )). The spectroscopic data showed that all the synthesised compounds produced a type II red shift of the heme Soret band indicating either direct binding to heme iron or (where less extensive Soret shifts are observed) putative indirect binding via an interstitial water molecule. Evaluation of biological and physicochemical properties identified the following as requirements for activity: LogP >4, H-bond acceptors/H-bond donors 4/0, number of rotatable bonds 5–6, molecular volume >340 ų, topological polar surface area <40 Ų.     

Unravelling the Role of Water in Ultrafast Excited-State Relaxation Dynamics within Nano-Architectures of Chlorophyll a

Water plays a pivotal role in structural stability of supramolecular pigment assemblies designed for natural light harvesting (for example, chlorosome antenna complex) as well as their artificial analogs. However, the dynamic role of water in the context of excite-state relaxation has not been explored till date, which we report here. Using femtosecond transient absorption spectroscopy, we investigate the excited-state dynamics of two types of nano-scale assemblies of chlorophyll a with different structural motifs, rod-shaped and micellar assemblies, that depend on the water content. We show how water participates in excess energy dissipation by vibrational cooling of the non-thermally populated Q_y band at different rates in different types of clusters but exhibits no polar solvation dynamics. For the micelles, we observe a bifurcation of stimulated emission line shape, whereas a positive-to-negative switching of differential absorption is observed for the rods; both these observations are correlated with their specific structural aspects. Density functional theory calculations reveal two possible stable ground state geometries of dimers, accounting for the bifurcation of line shape in micelles. Thus, our study elucidates water-mediated structure–function relationship within these pigment assemblies.     

Localization of fringes produced by rotation of the recording plate in focused-image holography

The equations determining the localization of interference fringes produced by rotation of the photographic plate in ‘focused-image holography’ are derived for an arbitrary cylindrical surface. The important properties of fringe localization are discussed and are experimentally verified.     

Experimental study of transient heat transfer characteristics of single-phase natural convection in multidimensional porous bed with volumetric heat generation

Natural convection in an internally heated porous bed of height and diameter of 450 mm and 500 mm, respectively, and superposed with the fluid layer has been experimentally investigated. The onset of natural convection in the bed is indicated by change in the rate of temperature rise within the bed. An empirical model based on local Nusselt number and local Rayleigh number has been developed. A comparison of the present model with the models in literature is made to draw out the differences between the local heat transfer of large multidimensional beds and the average heat transfer of small beds.     

One Pot One Step Photoconversion of Pulvinic Acid Dilactone to p-Methoxyvulpinic Acid

The utility of singlet oxygen-methanol as a reagent for nuclear methoxylation of complex organic natural products is illustrated by a one pot one step photoconversion of pulvinic acid dilactone to p-methoxyvulpinic acid. The study is important from biogenetic considerations.     

Calix[4]arene-based ditopic receptors for simultaneous recognition of fluoride and cobalt(II) ions

A series of calix[4]arene based ditopic receptors possessing bipyridyl and hydrazone units have been synthesized and evaluated for ionic recognition. It has been observed that the synthesized derivatives function as allosteric receptors for simultaneous recognition of Co²⁺and F^? ions through non-covalent interactions. Significant bathochromic shifts in the UV–visible spectrum with a profound colour change promise their use to engineer novel applications.     

Identification of groundwater discharge in Cuddalore coast,Tamil Nadu using radium isotopes

For the optimal exploitation and management of coastal aquifers of Tamil Nadu, it is essential to evaluate the groundwater outflow into the sea also called as submarine groundwater discharge. In this study, radium isotopes (^223,224Ra) were employed to understand the groundwater discharge in coastal areas of Cuddalore district, Tamil Nadu. Sea water samples (100 L) were collected from various locations of Cuddalore coast in October 2011 and passed through Mn-impregnated acrylic fiber columns. These acrylic columns were analyzed for ^223,224Ra activities using radium delayed coincidence counter. The observed higher activities of ^223,224Ra excess (0.02 ± 0.001–3.28 ± 0.16 and 64 ± 3–380 ± 19 mBq/100 L respectively) indicate that groundwater discharge occurs in this coastal region.     

An organocatalytic synthesis of N-sulfonyl imines using chloramine-T in aqueous medium

N-Sulfonyl imines have been synthesized in good to excellent yields from aldehydes and chloramine-T using proline as an organocatalyst in aqueous medium at ambient temperature. The protocol is applicable to a wide range of aldehydes, especially enals exhibit remarkable efficiency in the reaction. The reaction presumably occurs via iminium activation and opens new avenues for the synthesis of N-sulfonyl imines under environmentally benign and mild conditions.