Department of Chemistry

Indian Institute of Technology Palakkad&nbsp;(IIT Palakkad or IIT PKD) is a public autonomous&nbsp;engineering&nbsp;and&nbsp;research&nbsp;institute located in&nbsp;Palakkad,&nbsp;Kerala. It was&nbsp;one of the five new&nbsp;IITs&nbsp;proposed in the&nbsp;2014 Union budget of India. The campus was inaugurated on 3 August 2015. The institute has 94 faculty, 978 students, and 63 non-teaching staffs.

IT Palakkad currently offers four-year Bachelor of Technology (B.Tech) and two years MS programmes in 8 different engineering disciplines including&nbsp;Computer Science, Electrical, Mechanical, Civil among others.

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IIT Palakkad

The major route for elimination of 4-hydroxy-2-(E)-nonenal (4-HNE) has long been considered to be through glutathionylation and eventual excretion as a mercapturic acid conjugate. To better quantitate the glutathionylation process, we developed a sensitive LC-MS/MS method for the detection of glutathione (GSH) conjugates of 4-hydroxy-2-(E)-alkenal enantiomers having a carbon skeleton of C5 to C12. The newly developed method enabled us to quantify 4-hydroxy-2-(E)- alkenal-glutathione diastereomers in various organs, i.e., liver, heart, and brain. We identified the addition of iodoacetic acid as a critical step during sample preparation to avoid an overestimation of glutathione-alkenal conjugation. Specifically, we found that in the absence of a quenching step reduced GSH and 4-hydroxy-2-(E)-alkenals react very rapidly during the extraction and concentration steps of sample preparation. Rat liver perfused with d11-4-hydroxy-2-(E)-nonenal (d11-4-HNE) revealed enantioselective conjugation with GSH and transportation out of the liver. In the d11-4-HNE-perfused rat livers, the amount of d 11-(S)-4-HNE-GSH released from the rat liver was higher than that of d11-(R)-4-HNE-GSH, and more d11-(R)-4-HNE-GSH than d 11-(S)-4-HNE-GSH remained in the perfused liver tissues. Overall, the glutathionylation pathway was found to account for only 8.7% of the disposition of 4-HNE, whereas catabolism to acetyl-CoA, propionyl-CoA, and formate represented the major detoxification pathway. © 2014 Elsevier Inc.

World University root node

Free Radical Biology and Medicine

Glutathionylated 4-hydroxy-2-(E)-alkenal enantiomers in rat organs and their contributions toward the disposal of 4-hydroxy-2-(E)-nonenal in rat liver

CHEMICAL COMMUNICATIONS

Chloride sensing via suppression of excited state intramolecular proton transfer in squaramides (vol 49, pg 1633, 2013)

A new design strategy is described for chloride ion sensors based on suppression of excited state intramolecular proton transfer in squaramides as a fluorescence “turn on” mechanism. © 2013 The Royal Society of Chemistry.

Chemical Communications

Chloride sensing via suppression of excited state intramolecular proton transfer in squaramides

With the objective of investigating the direct conversion of inorganic carbonates such as CaCO3 to hydrocarbons, assisted by transition metal ions, we have carried out studies on CaCO3 in an intimate admixture with iron oxides (FeCaCO) with a wide range of Fe/Ca mole ratios (x), prepared by co-precipitation. The hydrogen reduction of FeCaCO at 673 K gives up to 23% yield of the hydrocarbons CH4, C2H4, C2H6 and C3H8, leaving solid iron residues in the form of iron metal, oxides and carbide particles. The yield of hydrocarbons increases with x and the conversion of hydrocarbons occurs through the formation of CO. While the total yield of hydrocarbons obtained by us is comparable to that in the Fischer-Tropsch synthesis, the selectivity for C 2-C3 hydrocarbons reported here is noteworthy. © The Royal Society of Chemistry 2013.

Fulltext

RSC Advances

Direct conversion of calcium carbonate to C1-C3 hydrocarbons

We recently reported that levulinate (4-ketopentanoate) is converted in the liver to 4-hydroxypentanoate, a drug of abuse, and that the formation of 4-hydroxypentanoate is stimulated by ethanol oxidation. We also identified 3 parallel β-oxidation pathways by which levulinate and 4-hydroxypentanoate are catabolized to propionyl-CoA and acetyl-CoA. We now report that levulinate forms three seven-carbon cyclical CoA esters by processes starting with the elongation of levulinyl-CoA by acetyl-CoA to 3,6-diketoheptanoyl-CoA. The latter γ-diketo CoA ester undergoes two parallel cyclization processes. One process yields a mixture of tautomers, i.e., cyclopentenyl- and cyclopentadienyl-acyl-CoAs. The second cyclization process yields a methyl-pyrrolyl-acetyl-CoA containing a nitrogen atom derived from the ε-nitrogen of lysine but without carbons from lysine. The cyclic CoA esters were identified in rat livers perfused with levulinate and in livers and brains from rats gavaged with calcium levulinate ± ethanol. Lastly, 3,6-diketoheptanoyl-CoA, like 2,5-diketohexane, pyrrolates free lysine and, presumably, lysine residues from proteins. This may represent a new pathway for protein pyrrolation. The cyclic CoA esters and related pyrrolation processes may play a role in the toxic effects of 4-hydroxypentanoate. © 2012 American Chemical Society.

Chemical Research in Toxicology

Metabolomics and mass isotopomer analysis as a strategy for pathway discovery: Pyrrolyl and cyclopentenyl derivatives of the pro-drug of abuse, levulinate

Sirt5, localized in the mitochondria, is a member of sirtuin family of NAD +dependent deacetylases. Sirt5 was shown to deacetylate and activate carbamoyl phosphate synthase 1. Most recently, Sirt5 was reported to be the predominant protein desuccinylase and demalonylase in the mitochondria because the ablation of Sirt5 enhanced the global succinylation and malonylation of mitochondrial proteins, including many metabolic enzymes. In order to determine the physiological role of Sirt5 in metabolic homeostasis, we generated a germline Sirt5 deficient (Sirt5-/-) mouse model and performed a thorough metabolic characterization of this mouse line. Although a global protein hypersuccinylation and elevated serum ammonia during fasting were observed in our Sirt5-/-mouse model, Sirt5 deficiency did not lead to any overt metabolic abnormalities under either chow or high fat diet conditions. These observations suggest that Sirt5 is likely to be dispensable for the metabolic homeostasis under the basal conditions.

Scientific Reports

Metabolic characterization of a Sirt5 deficient mouse model

Thermolysis of [(Cp*RuCO)2B2H6] (1; Cp* = η5-C5Me5) with [Ru 3(CO)12] yielded the trimetallaborane [(Cp*RuCO) 3(μ3-H)BH] (2) and a number of homometallic boride clusters: [Cp*RuCO{Ru(CO)3}4B] (3), [(Cp*Ru)2{Ru2(CO)8}BH] (4) and [(Cp*Ru)2{Ru4(CO)12}BH] (5). Compound 2 is isoelectronic and isostructural with the triply bridged borylene compounds [(μ3-BH)(Cp*RuCO)2(μ-CO){Fe(CO)3}] (6) and [(μ3-BH)(Cp*RuCO)2(μ-H)(μ-CO) {Mn(CO)3}] (7), where the [μ3-BH] moiety occupies the apical position. To test if compound 2 undergoes hydroboration reactions with alkynes, as observed with 6, we performed the reaction of 2 with the same set of alkynes under photolytic conditions. However, neither 2 nor 7 undergoes hydroboration to yield a vinyl-borylene complex. On the other hand, thermolysis of 6 with trimethylsilylethylene yielded the novel diruthenacarborane [1,1,7,7,7-(CO)5-2,3-(Cp*)2-μ-2,3-(CO) -μ3-1,2,3-(CO)-5-(SiMe3)-pileo-1,7,2,3,4,5-Fe 2Ru2C2BH] (8). The solid-state X-ray diffraction results suggest that 8 exhibits a pentagonal -bipyramidal geometry with one additional CO capping one of its faces. Cluster 3 is a boride cluster where boron is in the interstitial position of a square-pyramidal geometry, whereas compound 4 can be described as a tetraruthenium boride in which the Ru4 butterfly skeleton has an interstitial boron atom. Electronic structure calculations of compound 2 employing density functional theory (DFT) generate geometries in agreement with the structure determinations. The existence of a large HOMO-LUMO gap in 2 is in agreement with its high stability. Bonding patterns in the structure have been analyzed on the grounds of DFT calculations. Furthermore, the B3LYP-computed 11B and 1H chemical shifts for compound 2 precisely follow the experimentally measured values. All the compounds have been characterized by IR and 1H, 11B and 13C NMR spectroscopy and the geometries of the structures were unambiguously established by crystallographic analyses of 2-4 and 8. © 2013 American Chemical Society.

Organometallics

Chemistry of homo-and heterometallic bridged-borylene complexes

Supramolecular interactions of polynitroxides with γ-cyclodextrin (γ-CD) were used to control intramolecular electron spin-spin exchange couplings in these stable radicals. In the absence of γ-CD, the binitroxide T2 and trinitroxide T3 showed strong spin-spin coupling as evidenced by the high exchange coupling constant of J = 120 MHz for T2 in its EPR spectra. Host/guest complexes are formed upon addition of γ-CD to the polynitroxides where the nitroxide moiety interacts with the γ-CD cavity, which causes suppression of spin exchange. By variation of the host/guest ratio, the nature of a trinitroxide spin system can be tuned from a three-spin to a two-spin to a one-spin system. In addition to the host/guest ratio, the spin exchange coupling can also be tuned by temperature, which shifts the equilibrium between CD-encapsulated nitroxides and free nitroxides. © 2013 The Royal Society of Chemistry.

Control of spin-spin exchange interactions in polynitroxides through inclusion within γ-cyclodextrin

Coordination self-assembly of a series of tetranuclear Pt(ii) macrocycles containing an organometallic backbone incorporating ethynyl functionality is presented. The 1:1 combination of a linear acceptor 1,4-bis[trans-Pt(PEt 3)2(NO3)(ethynyl)]benzene (1) with three different dipyridyl donor 'clips' (La-Lc) afforded three [2 + 2] self-assembled PtII4 macrocycles (2a-2c) in quantitative yields, respectively [La = 1,3-bis(3-pyridyl) isothalamide; Lb = 1,3-bis(3-pyridyl)ethynylbenzene; Lc = 1,8-bis(4-pyridyl)ethynylanthracene]. These macrocycles were characterized by multinuclear NMR (1H and 31P); ESI-MS spectroscopy and the molecular structures of 2a and 2b were established by single crystal X-ray diffraction analysis. These macrocycles (2a-2c) are fluorescent in nature. The amide functionalized macrocycle 2a is used as a receptor to check the binding affinity of aliphatic acyclic dicarboxylic acids. Such binding affinity is examined using fluorescence and UV-Vis spectroscopic methods. A solution state fluorescence study showed that macrocycle 2a selectively binds (KSV = 1.4 × 104 M-1) maleic acid by subsequent enhancement in emission intensity. Other aliphatic dicarboxylic acids such as fumaric, succinic, adipic, mesaconic and itaconic acids caused no change in the emission spectra; thereby demonstrating its potential use as a macrocyclic receptor in distinction of maleic acid from other aliphatic dicarboxylic acids. © 2013 The Royal Society of Chemistry.

Dalton Transactions

Coordination self-assembly of tetranuclear Pt(ii) macrocycles with an organometallic backbone for sensing of acyclic dicarboxylic acids

Room temperature photolysis of a triply-bridged borylene complex, {[}(3-BH)(Cp{*}RuCO)2(-CO)Fe(CO)3] (1a; Cp{*}=C5Me5), in the presence of a series of alkynes, 1,2-diphenylethyne, 1-phenyl-1-propyne, and 2-butyne led to the isolation of unprecedented vinyl-borylene complexes (Z)-{[}(Cp{*}RuCO)2(-CO)B(CR)(CHR)] (2: R, R=Ph; 3: R=Me, R=Ph; 4: R, R=Me). This reaction permits a hydroboration of alkyne through an anti-Markovnikov addition. In stark contrast, in the presence of phenylacetylene, a metallacarborane, closo-{[}1,2-(Cp{*}Ru)2(-CO)2\{Fe2(CO)5\}-4-Ph-4,5-C2BH2] (5a), is formed. A plausible mechanism has been proposed for the formation of vinyl-borylene complexes, which is supported by density functional theory (DFT) methods. Furthermore, the calculated 11BNMR chemical shifts accurately reflect the experimentally measured shifts. All the new compounds have been characterized in solution by mass spectrometry and IR, 1H, 11B, and 13CNMR spectroscopies and the structural types were unequivocally established by crystallographic analysis of 2, 5a, and 5b.

CHEMISTRY-A EUROPEAN JOURNAL

Syntheses and Characterization of New Vinyl-Borylene Complexes by the Hydroboration of Alkynes with {[}(μ3-BH)(Cp{*}RuCO)2(μ-CO)Fe(CO)3]