Noncovalent Bond Lengths and Their Cooperative Shortening: Dimers of Vancomycin Group Antibiotics in Crystals and in Solution

• Published in: Helvetica chimica acta 2003-05, Vol.86 (5), p.1359-1370
• Main Authors: Shiozawa, Hideyuki, Zerella, Rosa, Bardsley, Ben, Tuck, Kellie L., Williams, Dudley H.
• Format: Article
• Language: English
• ISSN: 0018-019X; 1522-2675
• DOI: 10.1002/hlca.200390123

A wide range of dimerisation constants (Kdim ca. 101–106 M−1) for various glycopeptide antibiotics have been determined. We consider these dimerisation constants in the light of the published X‐ray structures of the antibiotics, in particular, the relationship between Kdim and the length of a specified distance at the dimer interface. In the crystals, we find that this distance is smaller for strongly dimerising antibiotics and larger for weakly dimerising antibiotics. Thus, the dimerisation constant is correlated with tightness at the dimer interface. Despite the crystal‐packing forces exerted between adjacent dimer molecules in the crystals, the noncovalent bond distances at the dimer interface are correlated with the distances in solution (inferred from solution NMR data). These observations can account for the benefits in enthalpy, and costs in entropy, associated with positively cooperative binding.