STRUCTURAL REQUIREMENTS FOR RAPID METAL-ION INGRESS INTO HYDROXYETHYLATED TETRAAZA MACROCYCLES

Synthesis of two new bis(2-hydroxyethyl) substituted cyclam (1,4,8,11- tetraazacyclotetradecane) derivatives, 1,4-bis(2-hydroxyethyl)-8,11-di methylcyclam (1,4-DMHEC-14) and 1,11-bis(2-hydroxyethyl)-4,8-dimethylc yclam (1,11-DMHEC-14), has enabled a study of the effects of partial h ydroxyethylation of the nitrogen atoms in a macrocyclic ligand framewo rk to be made. The ligands were synthesised through the reaction of et hylene oxide with the appropriately methylated cyclam precursor. Stabi lity constants for complexes of these ligands with Co2+, Ni2+, Cu2+, Z n2+, Cd2+, Hg2+ and Pb2+ have been measured by potentiometric titratio n and are generally intermediate between those shown by tetramethylcyc lam (TMC-14) and tetrakis(2-hydroxyethyl)cyclam (THEC-14), consistent with a lower level of ligand stabilisation through internal hydrogen b ond formation than in THEC-14. Equilibration times noted during the po tentiometric titrations indicate that these bis(2-hydroxyethyl) ligand s, like THEC-14 and unlike TMC-14, facilitate rapid entry of the metal ion into the macrocyclic annulus demonstrating that two pendant 2-hyd roxyethyl arms, when located on adjacent nitrogen atoms, are sufficien t to generate facilitated entry. The crystal structures of both [Ni(1, 4-DMHEC-14)](ClO4)(2) and [Ni(1,11-DMHEC-14)](ClO4)(2) have been deter mined by a combined molecular mechanics and X-ray crystallography stud y and show that in each isomer both pendant donors are coordinated in a trans-relationship, in addition to the four nitrogen atoms, giving r ise to octahedral stereochemistry. In the former case the ligand is in the trans-III configuration whereas the latter complex has a trans-II geometry.