Using the modified-INDO finite perturbation theory of l3C chemical shifts, a set of "computer experiments" was performed to explore the geometrical dependence of the shielding of methyl groups in systems where steric effects may be expected. The conformational dependences of the computed methyl-group l3C shielding constants in «-butane and 2-butene systems were found to be substantial and to be qualitatively consistent with trends that have been popularly referred to as the 7 effect. However, inspection of the computed electron density distributions and details of the geometrical dependences lead to the suggestion that the mechanism of the 7 effect may be considerably more complex than the popularly accepted C-H bond polarization by nonbonded H~*H interactions. Calculations on systems in which two methane or ethane molecules are brought close enough together to emphasize intermolecular ~ interactions and calculations on «-pentane conformers similarly lead to a conclusion that the nature and conformational relationship of the bonding connecting the interacting methyl groups may be at least as important as the proximity of nonbonded hydrogens.(A) Steric Effects on 13C Shielding and the 7 Effect. In the early 1960's, as Paul and Grant1 were examining the l3C chemical shifts of linear alkanes with attention focused upon the possible existence of additivity relationships, an interesting pattern was uncovered. As Grant and Paul noted, and as can be seen in Table I in proceeding down the series from methane to propane, the chemical shift of the terminal carbon (Ci) moves increasingly toward lower shielding. The trend is reversed, however, for butane, in which the terminal carbon is more shielded than the terminal carbon of propane. This apparent reversal in trend has been noted in many saturated systems and has become known as "the 7 effect". This effect, as noted by Woolfenden and Grant,2 is also present in the alkenes but not in cumulenes or aromatics. An example of the 7 effect in alkenes is included in Table I, where it can be seen that the methyl carbons on both isomers of 2-butene are more shielded than the methyl carbon on propene. The effect is far greater for the cis isomer. This type of data led Woolfenden and Grant2 to suggest that the 7 effect was due to a through space interaction of "groups which have coiled back upon one another". Grant et al.2•3 went on to propose that this effect arose from electron repulsions between interacting C-H systems, which cause significant increases in the electron density about the carbon nucleus and, hence, it was argued, an increase in shielding. As a shorthand notation, we will refer to this as the "C-«-H-~*H-*-C" interpretation. As a specific example, let us consider «-butane, which is shown in both cis and trans configurations in Figure 1. In a gauche or cis configuration, the hydrogen atoms on the terminal methyl groups are close enough to one another to give rise, in the popular interpretation of the 7 effect, to electronic repulsions, inducing a polarization of electr...
13C chemical shifts and Jc,h coupling constants are reported for 17 5-substituted uracils. Overall, the chemical shifts at C-5 and C-6 of the 5-substituted uracils exhibit no obvious correlation with substituent electronegativity. Instead, when the 5-substituted uracils are considered as trisubstituted ethylenes, the chemical shift data are shown to be rationalized in terms of the ability of the C-5 substituent to behave as a mesomeric acceptor or donor. It is also demonstrated that the correlation of the chemical shifts at C-6 can be used to identify two categories of 5-substituted uracils whose parent deoxynucleotide derivatives are inhibitors of the enzyme, thymidylate synthetase. It is suggested that 13C nmr spectroscopy is a potentially useful tool for predicting the effectiveness of certain modified substrates as enzymatic inhibitors.Uracil and certain of its 5-substituted analogs are involved in a number of biochemically significant roles (i.e., constituents of RNA and DNA) in all(1) Presented in part at the 162nd National Meeting of the American
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