Cyclization Effect on pKa of the Side Chain of Aspartic Acid in Dipeptides: A DFT Study

Cyclic dipeptides are very important compounds that have a wide range of applications in pharmaceutical chemistry and life sciences. In the current work, the acidity of the side chain of aspartic acid was calculated for various linear and a cyclic dipeptide. pKa values were derived using the thermodynamics cycle and DFT/B3LYP approach. The obtained pKa values show strong acidity for cyclic with respect to linear dipeptides. We found an intramolecular hydrogen bond in cyclic dipeptide structure, which can be used to justify the increasing acidity of the side chain of Asp as compared to linear structures.