title: Solution equilibria of copper(II) complexation with N,N'-(2,2'-azanediylbis(ethane-2,1-diyl))dipicolinamide: a bio-distribution and dermal absorption study.
abstract: The protonation equilibria of a pentadentate ligand, N,N'-(2,2'-azanediylbis(ethane-2,1-diyl))dipicolinamide ([H(2)(5555)-N]) and the complexation of this ligand with Cu(II) Ca(II), Zn(II) and Ni(II) have been studied by pH-potentiometry, (1)H NMR spectroscopy and UV-vis spectrophotometry. (1)H NMR detected the protonation of the pyridyl groups and formation of Cu[H(2)(5555)-N]H species at low pH, while amide group deprotonation at higher pH resulted in the formation of Cu[H(2)(5555)-N]H(-1) and Cu[H(2)(5555)-N]H(-2) species in solution. Potentiometric detection of protonated species was limited by the acidic nature of the pyridyl nitrogen donors. From UV-vis spectroscopy it is suggested that the amide nitrogens are coordinated. This conclusion is supported by Molecular Mechanics calculations. Water-octanol partition coefficients for the Cu(II)-[H(2)(5555)-N] system indicated that although the Cu[H(2)(5555)-N]H(-1) species is largely hydrophilic, approximately 54% of the complex goes into the organic phase. This percentage is able to promote dermal absorption of copper with a calculated penetration rate of 1.92x10(-1)cmh(-1). This was confirmed by dermal absorption studies which illustrate the role of hydrophobicity in promoting percutaneous drug administration.
authors.affiliation: University of Cape Town, Department of Chemistry, Private Bag Rondebosch, Cape Town 7701, South Africa.
authors.forename: John N
authors.initials: JN
authors.lastname: Zvimba
authors.forename: Graham E
authors.initials: GE
authors.lastname: Jackson
mesh_terms: D020003:1-Octanol / Q000378:metabolism; D000577:Amides / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002614:Chelating Agents / Q000378:metabolism; D003301:Copper Radioisotopes / Q000378:metabolism*; D005260:Female; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D010848:Picolinic Acids / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D011199:Potentiometry; D012869:Skin Absorption / Q000187:drug effects; D012996:Solutions; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000577:Amides; D002614:Chelating Agents; D003301:Copper Radioisotopes; D010848:Picolinic Acids; D012996:Solutions; D012997:Solvents; C003142:picolinamide; D020003:1-Octanol