Calculating ¹³C NMR chemical shifts of large molecules using the eXtended ONIOM method at high accuracy with a low cost

Abstract

Fragmentation‐based methods for nuclear magnetic resonance (NMR) chemical shift calculations have become more and more popular in first‐principles calculations of large molecules. However, there are many options for a fragmentation‐based method to select, such as theoretical methods, fragmentation schemes, the number of levels of theory, etc. It is important to study the optimal combination of the options to achieve a good balance between accuracy and efficiency. Here we investigate different combinations of options used by a fragmentation‐based method, the eXtended ONIOM (XO) method, for 13C chemical shift calculations on a set of organic and biological molecules. We found that: (1) introducing Hartree‐Fock exchange into density functional theory (DFT) could reduce the calculation error due to fragmentation in contrast to pure DFT functionals, while a hybrid functional, xOPBE, is generally recommended; (2) fragmentation schemes generated from the molecular tailoring approach (MTA) with small level parameter n, for example, n = 2 and the degree‐based fragmentation method (DBFM) with n = 1, are sufficient to achieve satisfactory accuracy; (3) the two‐level XO (XO2) NMR calculation is superior to the calculation with only one level of theory, as the second level (i.e., low level) of theory provides a way to well describe the long‐range effect. These findings are beneficial to practical applications of fragmentation‐based methods for NMR chemical shift calculations of large molecules.