Pattuparambil R. Rajamohanan

LCST in poly(N-isopropylacrylamide) copolymers: high resolution proton NMR investigations

A series of copolymers of N-isopropylacrylamide (NIPA) and acryloyl amino acids were synthesized and conjugated with p-aminobenzamidine (PABA). The values of lower critical solution temperatures (LCSTs) of these polymers estimated by 1 H NMR were in agreement with those estimated by the turbidometric methods. The apparent shifts in the peak positions for the polymer with increasing temperature reported in the past are shown to be artifacts resulting from the deuterium lock experiment. The 1 H- 1 H NOESY experiments were carried out to distinguish the interactions between the protons in: (a) 6-amino caproic acid (6ACA) and NIPA and (b) PABA and NIPA. These explain the variation in the LCST of the polymers based on the contributions of the two monomers to the magnitude of the polymer-polymer interactions. The findings are further supported by proton spin-lattice relaxation time measurements.

Transition‐Metal‐Free Multicomponent Reactions Involving Arynes, N‐Heterocycles, and Isatins

Mix and match: With isoquinoline as the nucleophilic trigger, multicomponent reactions afforded spirooxazino isoquinoline derivatives, proceeding through 1,4-dipolar intermediates. The use of pyridine as a nucleophile furnished indolin-2-one derivatives, with the reaction likely proceeding through a pyridylidene intermediate.

Isolation, Purification and Characterization of Vinblastine and Vincristine from Endophytic Fungus Fusarium oxysporum Isolated from Catharanthus roseus

Endophytic fungi reside in a symbiotic fashion inside their host plants, mimic their chemistry and interestingly, produce the same natural products as their hosts and are thus being screened for the production of valuable compounds like taxol, camptothecin, podophyllotoxin, etc. Vinblastine and vincristine are excellent anti-cancer drugs but their current production using plants is non-abundant and expensive. In order to make these drugs readily available to the patients at affordable prices, we isolated the endophytic fungi from Catharanthus roseus plant and found a fungus AA-CRL-6 which produces vinblastine and vincristine in appreciable amounts. These drugs were purified by TLC and HPLC and characterized using UV-Vis spectroscopy, ESI-MS, MS/MS and 1H NMR. One liter of culture filtrate yielded 76 µg and 67 µg of vinblastine and vincristine respectively. This endophytic fungal strain was identified as Fusarium oxysporum based upon its cultural and morphological characteristics and internal transcribed spacer (ITS) sequence analysis.

Unusual retardation and enhancement in polymer dissolution : role of disengagement dynamics

This work addresses the issue of resolution of some unusual observations in the swelling-dissolving problem in polymers. There are observations showing several fold increase in the rate of dissolution when the residual solvent content is increased only marginally. Additionally, by using an in situ NMR technique to study dissolution, we have found the existence of an intermediate plateau in the dissolution curve indicating an unusual retardation in the rate of dissolution under certain conditions. Interestingly, this plateau disappears on either increasing the molecular weight of the polymer or on doing dissolution under shearing rather than under stagnant conditions. An improved model is proposed to explain these results, which cannot be explained by the existing models. The new feature is the incorporation of a kinetic model to relate the disengagement rate to the swelling rate, through the changing mobility of the disengaging macromolecule at the gel-liquid interface. The present study thus enables a clearer elucidation of the role of disengagement dynamics in the dissolution process.

Assembly of polyethyleneimine in the hexagonal mesophase of nonionic surfactant: effect of pH and temperature.

We investigate the dispersion of a pH responsive polymer, polyethyleneimine, PEI, in a hexagonal (H(1)) mesophase of a nonionic surfactant, C(12)E(9), and water, at pH ranging from basic (pH = 12.8) to acidic (pH = 1). While the C(12)E(9)/H(2)O phase behavior is independent of pH, we demonstrate that, in the PEI/C(12)E(9)/H(2)O system, changing the pH influences PEI-C(12)E(9) interactions, and thus, influences the isotropic-H(1) phase transition. With decrease in pH, there is increasing protonation of the PEI chain, and consequently, the chain extends. We show, using a combination of SAXs, optical microscopy and visual experiments, that the inclusion of PEI in a 1:1 surfactant-water mixture, lowers the hexagonal-isotropic transition temperature, T(HI). At higher pH = 12.8, T(HI) shows a pronounced decrease from 50 to 13 °C on addition of PEI, and the PEI/C(12)E(9)/H(2)O system forms a transparent gel. At pH = 1, we observe qualitatively different behavior and an opaque gel forms below T(HI) = 25 °C. The isotropic-H(1) transition, in turn, influences the phase separation of PEI chains from the C(12)E(9)/H(2)O system. 2D NMR ROESY data provides evidence that there are strong surfactant-PEI interactions at high pH that significantly reduce at lower pH. The NMR data is in accord with molecular dynamics simulations that show that surfactants strongly aggregate with unprotonated PEI chains, but not with fully protonated chains; thus, in this system, the pH controls a cascade of microstructural organization: increasing pH decreases chain protonation and increases polymer-surfactant interactions, resulting in suppression of the isotropic-H(1) transition to lower temperatures, thus, influencing the phase separation of PEI from the surfactant/water system.

A Synthetic Zipper Peptide Motif Orchestrated via Co-operative Interplay of Hydrogen Bonding, Aromatic Stacking, and Backbone Chirality

Here, we report on a new class of synthetic zipper peptide which assumes its three-dimensional zipper-like structure via a co-operative interplay of hydrogen bonding, aromatic stacking, and backbone chirality. Structural studies carried out in both solid- and solution-state confirmed the zipper-like structural architecture assumed by the synthetic peptide which makes use of unusually remote inter-residual hydrogen-bonding and aromatic stacking interactions to attain its shape. The effect of chirality modulation and the extent of noncovalent forces in the structure stabilization have also been comprehensively explored via single-crystal X-ray diffraction and solution-state NMR studies. The results highlight the utility of noncovalent forces in engineering complex synthetic molecules with intriguing structural architectures.

Proton magnetic resonance imaging in hydrogels: volume phase transition in poly(N-isopropylacrylamide)

Proton Magnetic Resonance (PMR) Imaging has been used to study the volume-phase-transition in a thermoreversible gel. This is demonstrated in the LCST polymer poly(N-isopropylacrylamide), swollen in water. The volume-phase-transition is conveniently monitored through one-dimensional proton images. PMR images, derived from relaxation and diffusion weighted planar spin-echo experiments, provide insights on the hydration state of water and the motional state of polymer, in the fully swollen and collapsed states of the gel.

Self-diffusion of water in thermoreversible gels near volume transition: Model development and PFG NMR investigation*

Pulsed filed gradient spin echo (PFG-SE) NMR technique has been used to measure the self-diffusion coefficient (Dself) of water in a thermoreversible hydrogel, Poly(N-isopropylacrylamide). Dself, was measured as a function of temperature (−5–50°C) and hydration level. A theoretical model to predict Dself was built by using a combination of lattice fluid hydrogen bond theory and free volume theory. The fully swollen gel did not show any discontinuous change in Dself with temperature, Whereas, a partially swollen gel, showing the existence of two kinds of water having diffusivities differing by order of magnitude, exhibits a discontinuous change in Dself. These results were explained within the theoretical framework developed by us. The present work thus enables an elucidation of diffusion phenomenon at the volume transition point for the first time.

Oxidative Intramolecular 1,2-Amino-Oxygenation of Alkynes under AuI/AuIII Catalysis: Discovery of a Pyridinium-Oxazole Dyad as an Ionic Fluorophore

Oxidative intramolecular 1,2-amino-oxygenation reactions, combining gold(I)/gold(III) catalysis, is reported. The reaction provides efficient access to a structurally unique ionic pyridinium-oxazole dyad with tunable emission wavelengths. The application of these fluorophores as potential biomarkers has been investigated.

Tuning Emission Responses of a Triphenylamine Derivative in Host–Guest Complexes and an Unusual Dynamic Inclusion Phenomenon

A newly synthesized triphenylamine derivative (1Cl3) shows significant differences in inclusion complex formation with two different macrocyclic hosts, cucurbit[7]uril (CB[7]) and β-cyclodextrin (β-CD). Detailed investigations by NMR spectroscopy reveal that CB[7] forms a 1:3 host-guest complex ([1·3{CB[7]}]Cl3) in which three arms of 1Cl3 are bound to three host molecules. On the other hand, β-CD forms a dynamic 1:1 inclusion complex ([1·{β-CD}]Cl3) by binding to only one of the three arms of 1Cl3 at a given time. The formation of a 1:1 host-guest complex with β-CD and 1:3 host-guest complex with CB[7] was also confirmed from the results of the isothermal titration calorimetric studies. Interestingly, 1Cl3 exhibits a rare dual emission property in solution at room temperature with the lower and higher energy bands arising from a locally excited state and an intramolecular charge-transfer transition, respectively. The difference in inclusion complex formation behavior of 1Cl3 with the two macrocyclic hosts results in the stabilization of different emission states in the two inclusion complexes. The fundamental difference in the electrostatic surface potentials, cavity polarities, and shapes of the two macrocyclic hosts could account for the formation of the different inclusion complexes with distinct luminescence responses.