Configurations of nickel-cyclam antiviral complexes and protein recognition

Tina M. Hunter, Iain W. McNae, Daniel P. Simpson, Alison M. Smith, Stephen Moggach, Fraser White, Malcolm D. Walkinshaw, Simon Parsons, Peter J. Sadler

Research output: Contribution to journalArticlepeer-review


Nickel (II)-xylylbicyclam is a potent anti-HIV agent and binds strongly to the CXCR4 co-receptor. We have investigated configurational equilibria of Ni-II-cyclam derivatives, since these are important for receptor recognition. Crystallographic studies show that both trans and cis configurations are readily formed: [Ni(cyclam)-(OAc)(2)](H2O)-H-. adopts the trans-III configuration with axial monodentate acetates, as does [Ni(benzylcyclam)(NO3)(2)] with axial nitrate ligands, whereas [Ni(benzylcyclam)(OAc)](OAc)(.)2H(2)O has an unusual folded cis-V configuration with Ni-II coordination to bidentate acetate. UV/Vis and NMR studies show that the octahedral trans-III configuration slowly converts to square-planar trans-1 in aqueous solution. For Ni-II-xylylbicyclam, a mixture of cis-V and trans-I configurations was detected in solution. X-ray diffraction studies showed that crystals of lysozyme soaked in Ni-II-cyclam or Ni(II)2-xylylbicyclam contain two major binding sites, one involving Ni-II coordination to Asp101 and hydrophobic interactions between the cyclam ring and Trp62 and Trp63, and the second hydrophobic interactions with Trp123. For Ni-II-cyclam bound to Asp101, the cis-V configuration predominates.

Original languageEnglish
Pages (from-to)40-50
Number of pages11
JournalChemistry - A European Journal
Issue number1
Publication statusPublished - 2007


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