The cyclization mechanism of <Emphasis Type="Italic">cis</Emphasis> DAA-DAA dipeptide: an ab initio study

The gas-phase cyclization mechanism of cis DAA-DAA dipeptide (where DAA stands for the earlier described double amino acid molecule of (NH₂)₂C(COOH)₂ formula while DAA-DAA indicates the system formed by two DAAs linked via the peptide bond) is investigated in the absence of any catalysts. Two different paths, concerted and stepwise, each leading to the same cyclo(DAA-DAA) dipeptide product are examined on the basis of theoretical calculations carried out at the CCSD(T)/aug-cc-pVDZ//MP2/aug-cc-pVDZ level. The final product of the cyclization was found to adopt boat conformation of the six-membered 2,5-diketopiperazine ring and its formation was predicted to be thermodynamically favored by ca. 3.7 kcal/mol. The activation barrier estimated for the concerted mechanism (39 kcal/mol) was found to be higher than each of two barriers (30–33 kcal/mol) on the stepwise route which indicates that the cyclization process leading to the cyclo(DAA-DAA) dipeptide formation is more plausible when operating along the stepwise pathway.