Carbon-13 Nuclear Magnetic Resonance Chemical Shift Calculation Protocol Applied to Rigid Triterpenes Molecules

Abstract

Nuclear magnetic resonance spectroscopy is one of the most powerful experimental techniques for obtaining three-dimensional structures of complex molecules, mainly for the analysis of the relative and absolute configurations of organic compounds. For this reason, this has become one of the most promising tools in the field of chemistry. From the theoretical point of view, advanced computational protocols have been developed for calculating nuclear magnetic resonance, mainly hydrogen-1 and carbon-13, parameters of isolated molecules, in which the environmental effects are neglected. These effects are predominantly related to the inherently large size of such systems, making conventional ab initio theories either very computationally demanding or even prohibitive. Despite the current advances in spectroscopic techniques, instances of revision of structures erroneously established for natural products are still common in the literature. Therefore, it is still necessary the development of quantum-chemical protocols that may assist in the correct structural determination of these compounds. This work aimed to test a universal scaling factor, based on a linear regression, for the calculation of carbon-13 nuclear magnetic resonance chemical shifts for rigid molecules, which has low computational cost and great accuracy to aid in the structural determination of natural products. The carbon-13 chemical shifts were calculated using the mPW1PW91/3-21G level of theory. Scaled chemical shifts were obtained according to the relation: 1.14x(calculated chemical shifts)–4.71. To test the application of the created scaling factor to problems related to stereochemistry, we investigated its ability to differentiate pentacyclic triterpenes regioisomers. Our results show that the mPW1PW91/3-21G//PM7 level of theory applied to the calculations, together with the use of the scaling factor, is an efficient and low-cost tool as an alternative to computational requirement approaches, usually applied to the calculation of carbon-13 nuclear magnetic resonance chemical shifts.