K M Muraleedharan

The ability of α,β2,3-hybrid peptides with a heterochiral backbone to exist in a helical, extended, or partially folded state depending on the solvation conditions employed was investigated. The preference was found to be directly dictated by Cα-Cβ torsions in the β-residues. α,β-Hybrid peptides with a heterochiral backbone show the ability to exist in a helical, extended, or partially folded conformation depending on the solvation conditions employed.

The self-assembly of non-ionic amphiphiles with a hydroxylated oxanorbornane head-group was controlled using amino acid units as spacers between hydrophilic and lipophilic domains to get spherical supramolecular aggregates. The ability of these systems to harbour therapeutic agents like ibuprofen, and their drug-release profiles were evaluated. Apart from directing the assembly, the intervening amino acid unit was found to help in drug entrapment as well. The presence of cholesterol improved their drug-loading ability, and an encapsulation efficiency of up to 66% was shown by the formulation containing the phenylalanine residue as the spacer (NC1c). There was no burst release, and 45% drug release was observed at the end of 24 h in this case (cf. soyaphosphatidylcholine based formulation = 49%). The results from SEM, Cryo-TEM, PXRD and confocal microscopic studies with some insights into molecular packing in this class of aggregates are also included.

Peptide segments with centrally placed sulfamide groups showed a remarkable tendency to adopt a turn conformation and exhibited supramolecular topologies like 'helical stacks' and 'hairpin sheets' through a highly coordinated array of strong and weak hydrogen bonds. This journal is

The use of oxanorbornane-based sugar-like surfaces in the development of new amphiphilic systems is demonstrated. Crystallographic analysis and results from aggregation studies showed their close resemblance to glycolipids. © The Royal Society of Chemistry 2012.

A design approach that incorporates structural requirements for the formation of a 1D assembly, fibril stability, and fibril–fibril interactions for gelation was attempted by using amino acid-based sulfamides with the general structure Aa-NH-SO2-NH-Aa (Aa=amino acid). A preference for 1D assembly alone was not a sufficient condition for gelation, which became evident from studies involving sulfamide esters 1–5. Reducing the crystallization tendency without hindering unidirectional growth was executed through diacids of the sulfamide precursors with various amines that form an envelope around the sulfamide core through salt bridges. This strategy was fruitful, and gels of a wide variety of solvents could be formed by varying the acid and amine components. The use of dodecylamine or benzylamine, which could stabilize the molecular layers through alkylchain segregation or π–π interactions improved the gelation tendency, whereas the nature of the amino acid side chain, especially the rotational freedom and hydrophobicity, had a direct role in dictating the solvent preference. Crystallographic studies of these two-component systems gave molecular- level insight into the assembly and showed the importance of anisotropy in the distribution of secondary interactions in gelation.

A convenient synthetic approach toward nucleoside analogs where β-hydroxyphosphonate- or 1,2-dihydroxy units are connected to the nucleic acid base through a triazole spacer is discussed.

Unfolding of helical trans-β2,3-hybrid peptides with (α-β)nα composition, when executed by increasing solvent polarity or temperature, proceeded in a systematic manner with the turns unwinding sequentially; C-terminal region of these peptides were first to unwind and the process propagated towards N terminus with more and more β residues equilibrating from the gauche to the anti rotameric state across Cα£Cβ. This is evidenced by clear change in their CβH signal splitting, 3JCαH-CβH values, and sequential disappearance of i,i+2 NOEs. Helix-strand hybrid: Unfolding of helical trans-β2,3-hybrid peptides with (α-β)nα composition when executed by increasing solvent polarity or temperature, proceeded in a systematic manner with the turns unwinding sequentially; the C-terminal region of these peptides were first to unwind and the process propagated towards the N terminus with more and more β residues equilibrating from gauche to anti rotameric states across Cα£Cβ.

This report introduces N-methylpyrrolidone hydroperoxide (NMPOOH)/base as an excellent reagent system for hydroxy-directed syn selective epoxidation of electron-deficient olefins, characterized by high diastereoselectivity, short reaction times and remarkable chemoselectivity, especially in presence of oxidatively labile nitrogen or sulfur atoms. NMPOOH also proves efficient in the oxidation of electron-deficient aromatic aldehydes, in the removal of oxazolidinone chiral auxiliary, and in the functionalization of alkenes and alkynes, showing wide application potential. Something kinda HOO-: This report introduces N-methylpyrrolidone hydroperoxide/base as an excellent system for the hydroxy-directed syn-selective epoxidation of electron-deficient olefins, characterized by high diastereoselectivity, short reaction times and remarkable chemoselectivity, especially in the presence of oxidatively labile nitrogen or sulfur atoms.

Anticancer activities of a series of benzisothiazolones having alkyl, aryl and aralkyl substituents on the nitrogen atom and the mechanistic basis of cytotoxicity are presented. Cellular responses like DNA laddering, disruption of mitochondrial membrane potential and caspase-3 activation on incubation of HeLa cells with representative compounds from this group suggested the induction of apoptosis through an intrinsic pathway. Their ability to arrest the cell cycle at the G2/M phase was confirmed by flow cytometric analysis. © 2013 The Royal Society of Chemistry.

Chemical environment-dependent supramolecular assembly of 11-helical α,β2,3-hybrid peptide which give hexagonal or rod-like microcrystalline structures is demonstrated. Apart from the modulatory role by P123, sequential use of organic co-solvents during the initiation and propagation phases is shown to contribute to the size and shape regulation during molecular organization. Comparison of powder XRD data and thermal analysis results suggested that the molecular arrangement in these aggregates is similar to that in their crystals. © 2012 The Royal Society of Chemistry.