Mending Ties with Halogens. HALO–DP4+: An Approach for DP4+ Calculations in Organohalogenated Molecules

Abstract

The combined use of NMR spectroscopy and quantum chemical calculations has become a powerful strategy for 5 structural elucidation. However, halogenated compounds pose a particular challenge due to the so-called HALA effect, where heavy 6 atoms distort the shielding of nearby light atoms, often leading to misleading predictions. Although a common workaround is to 7 discard affected signals, this approach fails in polyhalogenated systems, where too much valuable information is lost. In this study, we 8 systematically explored a range of strategies to mitigate the HALA effect across different levels of theory and probability-based 9 methods: DP4, MM-DP4+, and DP4+. This comprehensive analysis led us to develop HALO−DP4+, a simple yet robust correction10 protocol that significantly improves performance and can be universally applied regardless level of theory used. To streamline its use, 11 we updated our DP4+App to fully automate the correction process, making HALO−DP4+ readily accessible for routine structure 12 determination, even in challenging halogenated frameworks.