Halogen Bonding Propensity in Solution: Direct Observation and Computational Prediction.

Halogen-bonded complexes are often designed by consideration of electrostatic potential (ESP) predictions. ESP predictions do not capture the myriad variables associated with halogen bond (XB) donors and acceptors; thus, binding interaction cannot be quantitatively predicted. Here, a discrepancy between predictions based on ESP energy difference (ΔVs ) and computed gas phase binding energy (ΔEbind ) motivated the experimental determination of the relative strength of halogen bonding interactions in solution by Raman spectroscopic observation of complexes formed from interacting five iodobenzene-derived XB donors and four pyridine XB acceptors. Evaluation of ΔEbind coupled with absolutely-localized molecular orbital energy decomposition analysis (ALMO-EDA) deconvolutes halogen bonding energy contributions and reveals a prominent role for charge transfer (CT) interactions. Raman spectra reveal ΔEbind accurately predicts stronger interactions within iodopentafluorobenzene (IPFB) complexes than with 1-iodo-3,5-dinitrobenzene (IDNB) complexes even though IPFB has similar electrostatics to IDNB and contains a smaller σ-hole.