Coordination Chemistry of Borane in Solution: Application to a STING Agonist

Equilibrium constants were determined for ligand exchange reactions of borane complexes with various oxygen, sulfur, nitrogen, and phosphorus nucleophiles in solution, and a binding affinity scale was built spanning a range of 12 orders of magnitude. While the Keq are minimally dependent on the solvent, the rate of ligand exchange varies significantly. The fastest and slowest rates were observed in THF and CDCl3, respectively. Moreover, the ligand exchange rate differs in a very broad range depending on stability of the starting complex. Binding of BH3 was found to be much more sensitive to steric factors than protonation. Comparing nitrogen bases having equal steric properties, a linear correlation of BH3 binding affinity vs. Brønsted acidity was found. This correlation can be used to quickly estimate the BH3 binding affinity of a substrate if pKa is known. Kinetic studies suggest the ligand exchange to occur as a bimolecular SN2 reaction unless other nucleophilic species were present in the reaction mixture. Where does the boron go? Equilibrium constants were determined for ligand exchange reactions of borane complexes with various O, S, N and P nucleophiles in solution, and a binding affinity scale was built spanning a range of 12 orders of magnitude. Kinetic studies suggest the ligand exchange to occur as a bimolecular SN2 reaction. The obtained knowledge was applied to understand binding and stability of the corresponding adducts of a complex drug molecule having multiple potential nucleophilic sites.