Exploring the dynamics of halogen and hydrogen bonds in halogenated coumarins

Abstract

Abstract Halogen bonds find application in supramolecular chemistry, DNA Holliday junction, drug design, organic catalysis and various other fields. Coumarin derivatives are high in demand due to their application in photochemotherapy, drugs and other cancer treatments. Halogenated coumarins are widely known for their biological activities. There exists a competition between the halogen bond and hydrogen bond in singly hydrated halogenated coumarins. The competition between hydrogen and halogen bonding interactions in 3-halogenated 4-hydroxyl coumarin [coumarin derivative; halogen, X = F (A), Cl (B), Br (C), I (D)] with water molecule in the corresponding binding regions C3–X and C2=O4 is studied. This study was conducted using PBE0 D3BJ with augmented correlation consistent basis set in order to include the diffuse functions. Improved findings for non-bonded distances and much more distinct intramolecular effects were obtained using BJ-damping. In the singly-hydrated systems, the water molecule forms a hydrogen bond with C2=O4 in all the halogenated molecules, whereas halogen bonding between the water oxygen and C2–X exists only in the case of X = Br (C) and I (D). The absence of a halogen-bonded structure in singly-hydrated chlorine and fluorine substituted coumarin derivative is therefore attributed to the competing hydrogen-bonding interaction with C2=O4. RDG scatter plot as well QTAIM analysis implied that halogen bond exists between water molecule and the coumarin derivative. Further, the most modern local energy decomposition (LED) analysis of intermolecular interaction was also studied using DLPNO-CCSD(T). Finally, ab initio molecular dynamics was also performed.