Comparative biophysical studies of sartan class drug molecules losartan and candesartan (CV-11974) with membrane bilayers.

The interactions of the antihypertensive AT(1) antagonists candesartan and losartan with membrane bilayers were studied through the application of DSC, Raman, and solid state (31)P NMR spectroscopies. (1)H and (13)C NMR resonances of candesartan were assigned on the basis of 1D and 2D NMR spectroscopy. A (31)P CP NMR broadline fitting methodology in combination with ab initio computations was implemented and, in conjunction with DSC and Raman results, provided valuable information regarding the perturbation, localization, orientation, and dynamic properties of the drugs in membrane models.

EPR line-shape anisotropy and hyperfine shift of methyl radicals in solid Ne, Ar, Kr, and p-H2 gas matrices.

Earlier studies have shown that pure quantum mechanical effects on the "light" methyl radical at low temperature minimize the anisotropy of CW EPR spectra to a high resolution character, and new experiments under different conditions display a small additional electron paramagnetic resonance (EPR) line-shape anisotropy. In this work the effects of the solid H(2) quantum matrix and three other typical solid noble-gas matrices on the spectral anisotropy and the hyperfine interaction (hfi) constant of trapped methyl radicals presented as matrix shifts (deviation from the value in free space) are studied in some detail. Experimental EPR data at liquid-He temperatures were used to explore the dependence of the additional broadening and the spectral anisotropy of the hosted methyl radicals and to correlate the experimental spectral anisotropy to the matrix-radical interaction.

Development of a CP 31P NMR broadline simulation methodology for studying the interactions of antihypertensive AT1 antagonist losartan with phospholipid bilayers.

A cross-polarization (CP) (31)P NMR broadline simulation methodology was developed for studying the effects of drugs in phospholipids bilayers. Based on seven-parameter fittings, this methodology provided information concerning the conformational changes and dynamics effects of losartan in the polar region of the dipalmitoylphosphatidylcholine bilayers. The test molecule for this study was losartan, an antihypertensive drug known to exert its effect on AT(1) transmembrane receptors.