Dhrubajyoti Talukdar

A green synthesis of symmetrical bis(indol-3-yl)methanes using phosphate-impregnated titania catalyst under solvent free grinding conditions

Abstract An efficient, chemoselective method for the preparation of bis(indol-3-yl)methanes from aldehydes and indoles using phosphate-impregnated titania as the reusable catalyst under solvent-free grinding conditions is reported. The desired products were obtained in excellent yields with tolerability to functional groups such as −OMe, −Me, −Cl, −NO2, and −OH in a simple and environmentally benign procedure.

A Small Insulinomimetic Molecule Also Improves Insulin Sensitivity in Diabetic Mice

Dramatic increase of diabetes over the globe is in tandem with the increase in insulin requirement. This is because destruction and dysfunction of pancreatic β-cells are of common occurrence in both Type1 diabetes and Type2 diabetes, and insulin injection becomes a compulsion. Because of several problems associated with insulin injection, orally active insulin mimetic compounds would be ideal substitute. Here we report a small molecule, a peroxyvanadate compound i.e. DmpzH[VO(O2)2(dmpz)], henceforth referred as dmp, which specifically binds to insulin receptor with considerable affinity (KD-1.17μM) thus activating insulin receptor tyrosine kinase and its downstream signaling molecules resulting increased uptake of [14C] 2 Deoxy-glucose. Oral administration of dmp to streptozotocin treated BALB/c mice lowers blood glucose level and markedly stimulates glucose and fatty acid uptake by skeletal muscle and adipose tissue respectively. In db/db mice, it greatly improves insulin sensitivity through excess expression of PPARγ and its target genes i.e. adiponectin, CD36 and aP2. Study on the underlying mechanism demonstrated that excess expression of Wnt3a decreased PPARγ whereas dmp suppression of Wnt3a gene increased PPARγ expression which subsequently augmented adiponectin. Increased production of adiponectin in db/db mice due to dmp effected lowering of circulatory TG and FFA levels, activates AMPK in skeletal muscle and this stimulates mitochondrial biogenesis and bioenergetics. Decrease of lipid load along with increased mitochondrial activity greatly improves energy homeostasis which has been found to be correlated with the increased insulin sensitivity. The results obtained with dmp, therefore, strongly indicate that dmp could be a potential candidate for insulin replacement therapy.

Constructing two dimensional amide porous polymer to promote selective oxidation reactions

The covalent organic polymer synthesis is an elegant way to design materials with various topologies and explore new structures and properties. Herein, we report the synthesis of a novel porous polymer framework with the [3 + 2] structure motif via the condensation of 1,3,5-benzenetricarbonyl trichloride and p-phenylenediamine. The resulting highly stable mesoporous 2D framework material exhibits continuous conjugation of π-electronic system. Apart from gas adsorption properties, this material shows remarkable catalytic activity manifested by the conjugated π-cloud and amide functionality in selective oxidation reactions. Utmost selectivity of the reaction that exclusively yields aldehydes from benzyl alcohols via a free radical pathway is proposed and demonstrated. This is one of the rare cases of any organic polymer material acting as an outstanding organic catalyst with no metal add-ons.

Attenuation of macrophage accumulation and polarisation in obese diabetic mice by a small molecule significantly improved insulin sensitivity

Accumulation and polarization of anti-inflammatory M2 to proinflammatory M1 macrophage in the adipose tissue of obese diabetic mice is an important pathogenic signature. It worsens lipid induced inflammation and insulin resistance. Here we demonstrate that a small molecule, a peroxyvanadate compound i.e. DmpzH [VO(O2)2 (dmpz)] or dmp, could robustly decrease macrophage infiltration, accumulation and their polarization in high fat diet (HFD) induced obese diabetic mice. In searching the underlying mechanism it was revealed that SIRT1 level was strikingly low in the inflamed adipose tissue of HFD mice as compared to mice fed with standard diet (SD). Administration of dmp markedly increased SIRT1 level by inducing its gene expression with a consequent decrease in macrophage population. Elevation of SIRT1 coincided with the decrease of MCP1, Fetuin-A (FetA) and IFNγ. Since MCP1 and FetA drive macrophage to inflamed adipose tissue and IFNγ promotes M2 to M1 transformation, both recruitment and M1 induced inflammation were found to be significantly repressed by dmp. In addressing the question about how dmp induced excess SIRT1 could reduce MCP1, FetA and IFNγ levels, we found that it was due to the inactivation of NFκB because of its deacetylation by SIRT1. Since NFκB is the transcriptional regulator of these molecules, their expressions were significantly suppressed and that caused sharp decline in macrophage recruitment and their polarity to M1. This effected a marked fall in proinflammatory cytokine level which significantly improved insulin sensitivity. dmp is likely to be the first molecule that rescues inflammatory burden contributed by macrophage in obese diabetic mice adipose tissue which causes significant increase in insulin sensitivity therefore it may be a meaningful choice to treat type 2 diabetes.

Tapping electronic properties of amide porous polymer to promote selective oxidation reactions

Covalent organic framework materials are crystalline polymers with periodic ordering of organic building blocks and/or linkers exhibit wonderful applications in gas storage, conductive materials, energy storage and conversion, and to promote catalysis [1-3]. We report here the synthesis of a novel porous polymer framework with [3+2] structure motif via the condensation of 1,3,5-benzenetricarbonyl trichloride and p-phenylenediamine and characterized by FT-IR, TGA, PXRD, BET, SEM, TEM, 13C-CPMAS etc. The resulting highly stable mesoporous 2D framework material exhibits continuous conjugation of πelectronic system confirmed by solid state UV-Vis DR spectroscopy. Apart from gas adsorption properties, this material shows remarkable catalytic activity manifested by extremely low band gap of the conjugated π-cloud. The reaction pathway of benzyl alcohols via the formation of free radicals to only the corresponding aldehydes is highly selective supported by calculations on Dmol3 and Gaussian09 platforms. This is one of the rare cases of any organic polymer material acting as an outstanding organic catalyst with no metal add-ons. [1] Côté, A. P. et al. (2005). Science. 310, 1166−1170. [2] Shinde, D. B. et al. Chem. Commun. 2015, 51, 310─313. [3] Khatioda, R. et al. communicated 2017.