RESUMEN
The conformational properties of three pyridoxine derivatives were studied by 1 H dynamic NMR spectroscopy. Conformational exchange caused by a rotation of 2-nytrophenyl group around one single C-C bond, of 2,4-dinitrophenyl substituent around two single C-O bonds, and twist-twist transformations of the seven-membered ketal cycle was observed by NMR experiments at low temperatures. Meanwhile, the conformational exchange of the acetal ring remains fast in the NMR timescale even at 198 K. The energy barriers for all observed conformational exchange processes were determined by the lineshape analysis of dynamic NMR spectra. The activation barriers of the 2-nitrophenyl group rotation were almost the same for all studied compounds, about 40-41 kJ/mol. The energy barriers of the conformational exchange processes of the 2,4-nitrophenyl group and the ketal cycle increased significantly up to 10 kJ/mol in comparison with previously studied compounds with similar structure. Copyright © 2016 John Wiley & Sons, Ltd.
RESUMEN
A series of pyridoxine derivatives was investigated by (1) H and 2D nuclear overhauser enhancement spectroscopy (NOESY) NMR. The free energies of activation for the pyridyl-oxygen rotation of the 2,4-dinitrophenyl ether of the seven-membered acetals of pyridoxine were measured by dynamic NMR. A conformational exchange between the chair and twist forms of the seven-membered acetal ring was confirmed by dynamic NMR and STO3G computations.
RESUMEN
Pluronic block copolymers L61 and L121 were reacted with succinic anhydride to produce, respectively, their mono- and bisderivatives with succinic acid. The critical micelle concentration of Pluronics decreased after modification. The modification of Pluronic L61 promoted its association with the plasma membrane of human cells and increased membrane damage, while the membranotropic activity of modified Pluronic L121 reduced compared to the initial copolymer. Modified Pluronics interfered with the viability, apoptosis induction and metabolism of A549 cells and skin fibroblasts to a much lesser extent presumably due to the introduction of succinic acid residue inhibited intracellular penetration of copolymers. Modified Pluronic L121 promoted the cellular uptake of doxorubicin and rhodamine 123 in A549 cells attributed to the inhibition of membrane P-glycoprotein. Our study provides an approach to assessing the mechanism of interaction of amphiphilic polymers with living cells and demonstrates that Pluronic-succinic acid conjugates can be used as safe and efficient modulators of intracellular drug delivery.