The natural abundance carbon-13 nuclear magnetic resonance spectra of 29 nucleosides, including those naturally occurring, are described. The spectra may be divided into two regions: that due to the nitrogen base ( -37-33 ppm) and that due to the ribose moiety (37-89 ppm). The relative invariance of the ribose carbon shifts with nitrogen base has enabled their assignment independent of base. Total assignments are also given for the carbon atoms in the pyrimidine and purine bases. The observed shifts for the naturally occurring nucleosides correlate at least qualitatively with MO parameters derived for the parent bases. Consequently, it is apparent that the electronic structure of the nucleosides is reflected in the carbon-13 shifts. Furthermore, the shifts correlate reasonably well with the known chemical reactivity of these molecules. A cautionary note is added to prevent misconceptions relating to the simplicity of the factors contributing to the carbon-13 chemical shift.Recent advances in the theory and instrumentation of nuclear magnetic resonance have made this technique most promising for studies of bioorganic and even biopolymer molecules. Since the pioneering work of the Jardetzkys,2 much progress has been made in the area of proton magnetic resonance (pmr) studies on the pyrimidine and purine bases, nucleosides, and nucleotides.3•4 The few protons on the pyrimidine or purine rings generally lead to well-resolved and easily interpretable pmr spectra which are dependent upon concentration, pH, and temperature, as well as other factors.4The pmr technique is limited in this area due to the need for sites in the molecular framework to be proton bearing.Carbon-13 magnetic resonance spectroscopy (cmr) affords an opportunity to study in detail the structure of the molecular framework, with only the exception of the heteroatom sites. The carbon-13 spectra of the unsubstituted bases purine5 and pyrimidine6 have been determined. The spectrum of purine5 provided the first example of the analysis of carbon-13 spectra of biologically important molecules and the ordering of the chemical shifts C-2, C-8, and C-6 differed from that noted for the corresponding directly bonded protons (6,2,8).7 A gross correlation of the carbon-13 shift data with theoretical estimates of charge density was observed suggesting that pmr shifts are somewhat less reliable in considerations of the relation between shift and charge. More recently correlation of the carbon-13 shifts with total charge has been shown to be more reliable.8 Further, the variation in the ordering of the (1) (a)

The circular dichroism data on 38 pyrimidine nucleosides, selected to provide a basis for a reliable index of furanose conformation as a function of its optical activity, are presented. The functional dependency of the B2u Cotton effect on the sugar-base torsion angle and on the specific pentose conformation is determined from theory and compared with experimental data. The theoretical description of the rotational strength as a function of the torsion angle agrees in every respect with available experimental data. Substituent effects on the signed magnitudes of the B2u rotational strength generally correlate quite well with theoretical expectations. The success of the theoretical calculations depend on giving up the Kirkwood-Tinoco coupled oscillator scheme where the transition moment vector is located at the center of gravity of the chromophore and, instead, breaking down the electric transition moment into bond contributions.In paper VIII of this series,1 it was shown that an analysis of the -* * Cotton effects of cyclopyrimidine nucleosides and several other rigid systems predicts their absolute stereochemical configuration. The method of analysis is an extension of the classical coupled oscillator theory of optical activity of Kuhn,2 which was reformulated in quantum mechanical terms

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The synthesis and Class III antiarrhythmic activity of a series of 4-[(methylsulfonyl)amino]benzamides and sulfonamides are described. Selected compounds show a potent Class III activity and are devoid of effects on conduction both in vitro (dog Purkinje fibers) and in vivo (anesthetized dogs). Compounds having a 2-aminobenzimidazole group were found to be the most potent, and one compound having this heterocycle (5, WAY-123,398) was selected for further characterization. Compound 5 was shown to have good oral bioavailability and a favorable hemodynamic profile to produce a 3-fold increase of the ventricular fibrillation threshold and to terminate ventricular fibrillation, restoring sinus rhythm in anesthetized dogs. Voltage-clamp studies in isolated myocytes show that 5 is a potent and specific blocker of the delayed rectifier potassium current (IK) at concentrations that cause significant prolongation of action potential duration.