Molecular level understanding of the role of aldehyde in vegetable‐aldehyde–collagen cross‐linking reaction

The role of formaldehyde (HCHO) in vegetable‐aldehyde–collagen cross‐linking reaction was investigated at the B3LYP/6‐31+G(d) level, where lysine (LYS) was used as model of collagen and catechin (EC) as model of condensed vegetable tannin. Atomic charge and Frontier molecular orbital analysis show that intermediates formed by HCHO reacting with LYS or EC, that is, M LYS , M EC‐6 , and M EC‐8 , still have both nucleophilic and electrophilic sites, which are elements to form ternary cross‐linking in vegetable‐aldehyde–collagen system. The analysis of energy gap between HOMO (highest occupied molecular orbit) and LUMO (lowest unoccupied molecular orbit) indicate that the intermediate of HCHO–LYS residues (M LYS ) can further react with free HCHO to form product P‐N(CH 2 OH) 2 (P‐N‐represents amino acid residue; N represents nitrogen atom on side chain), but the reaction of intermediate M LYS with free EC is difficult to take place. So, the probability of forming ternary cross‐linking structure of amino acid residue–HCHO–EC is small, if HCHO is added before vegetable tannin in vegetable‐aldehyde–collagen system. However, the reactions of EC–HCHO intermediates (M EC‐6 and M EC‐8 ) with free amino acids, HCHO–amino acid residue intermediate (M LYS ), as well as with other EC–HCHO intermediates (M EC‐6 and M EC‐8 ), are very easy to take place. The reaction enthalpy also shows that the cross‐linking tendency is favorable in thermodynamics. So, it can be deduced that covalent cross‐linking among amino side chain of collagen and vegetable tannin may take place when aldehyde is added after vegetable tannin. In this way, a multiple point cross‐linking reaction occurs to create a high stabilization of collagen. © 2011 Wiley Periodicals, Inc.