Preferential polymerization of 5-(aminomethyl)-2-furancarboxylic acid (AMFC) into a cyclic tripeptide

Theoretical justification for the preferential formation of an 18-membered cyclic oligopeptide 1 based on 5-(aminomethyl)-2-furancarboxylic acid (AMFC, 2), is attempted using ab initio quantum chemical calculations. The free energy values obtained from Hessian calculations show that while the formation of the higher order cyclized oligopeptides [HN-H2C-(furan)-CO](n) with n = 3, 4, is energetically favorable, the formation of the cyclic dipeptide 3 is thermodynamically unfavorable. Inclusion of the solvent in calculations enhances this preference further. A plausible explanation for this is the proximity of repulsive charges on the furan O atoms in the dimer 3. Details of geometric parameters and Mulliken charges support this possibility. The repulsion is enhanced, as low frequency modes of nuclear motion that bring these O atoms closer are active at room temperature.