Configurations of metallocyclams and relevance to anti-HIV activity.

Antiviral cyclam macrocycles block viral entry into cells by binding to the CXCR4 co-receptor. Cyclams bind transition metal ions strongly and can potentially form a range of trans (I-V) and cis configurations which may be recognised differently by co-receptor proteins. A survey of the CSD (crystallographic structural database) shows that the trans-III configuration is the most common in the solid state for complexes of cyclam itself. Other configurations can be induced by N-substitution or ternary complexation and by interaction with solvents in solution. We report X-ray structures for the square-planar trans-III complexes [Pd(cyclam)]Cl(2).2MeOH and the C-C linked dimer [Pd(2)(2,2'-bi-(1,4,8,11-tetraazacyclotetradecane))](ClO4)(4), in which the planes of the two cyclam rings are close to perpendicular (100.1 degrees ), and for tetra-N-benzyl-cyclam and its 5-coordinate Ni(II) complex [Ni(Bz(4)-cyclam)Cl]Cl which has the unusual trans-I configuration.