RESUMEN
The synthesis of a series of vinylated analogues of sphingosine-1-phosphate together with their unambiguous configurational assignment by VCD methods is reported. Among them, compound RBM10-8 can irreversibly inhibit human sphingosine-1-phosphate lyase (hS1PL) while behaving also as an enzyme substrate. These findings, together with the postulated mechanism for S1PL activity, reinforce the role of RBM10-8 as a new mechanism-based hS1PL inhibitor.
Asunto(s)
Aldehído-Liasas/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Aldehído-Liasas/química , Secuencia de Aminoácidos , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Estructura Molecular , EstereoisomerismoRESUMEN
The implementation of a strategy comprising the use of vibrational circular dichroism spectroscopy and DFT calculations allows determination of the solution-state conformational distribution in (-)-S-cotinine, giving further proof of the extra conformer-discriminating potential of this experimental technique, which may offer unique molecular fingerprints of subtly dissimilar molecular conformers of chiral samples. Natural bond orbital electronic structure calculations of the rotational barrier height between the two main conformers of the species indicate that hyperconjugative effects are the key force governing the conformational equilibrium. The negligible effect of the solvent's polarity over both structure and conformational energy profile supports this result.
RESUMEN
The gas-phase molecular structure of iodotrimethylsilane (ITMS) has been determined from electron diffraction data. Infrared and Raman spectra have been completely assigned. The experimental work is supported by ab initio HF and MP2 calculations for the gas-phase structure determination and DFT(B3LYP) calculations, combined with Pulay's SQM method, for the vibrational spectra data.
