The properties of a novel Gd3+-based MRI zinc sensor are reported. Unlike previously reported Gd3+-based MRI contrast agents, this agent (GdL) differs in that the agent alone binds only weakly with human serum albumin (HSA) while the 1:2 GdL:Zn2+ ternary complex binds strongly to HSA resulting in a substantial, three-fold increase in water proton relaxivity. The GdL complex is shown to have a relatively strong binding affinity for Zn2+ (KD = 33.6 nM), similar to the affinity of the Zn2+ ion with HSA alone. The agent detects as little as 30 μM Zn2+ in the presence of HSA by MRI in vitro, value slightly more than the total Zn2+ concentration in blood (∼20 μM). This combination of binding affinity constants and the high relaxivity of the agent when bound to HSA suggests that this new agent may be useful for detection of free Zn2+ ions in vivo without disrupting other important biological processes involving Zn2+.

A Zn2+ specific GdDOTA derivative containing two bis-(3-pyrazolyl) units was prepared and characterized. Unlike a previously reported Zn2+ binding agent, the new agent binds to human albumin both in the presence and absence of Zn2+.

Formation constants of Mn2+, Co2+, Ni2+, Cu2+, and Zn2+ complexes formed in aqueous solutions with 12membered and 13-membered macrocycles have been determined, and the solution electronic spectra have been studied. The 12-membered macrocycle, abbreviated as (12edtaen)H2, is 2,9-dioxo-l,4,7,10-tetraaza-4,7cyclododecanediacetic acid, and the 13-membered macrocycle, abbreviated as (13edtapn)H2, is 2,9-dioxo-l,4,7,10tetraaza-4,7-cyclotridecanediacetic acid. The structures of [Zn(Ci2Hi8N406)]'4H20 and [Mn(Ci3H2oN406)-( 2 )]2*7 2 have been determined by single-crystal X-ray analyses. The zinc complex crystallized in the monoclinic space group P2\ln with a -10.205(2) k,b = 9.599(2) Á, c = 19.431(3) Á, ß = 100.268 (2)°, and Z = 4. The coordination geometry around the zinc atom is distorted octahedral with five donor atoms (two amine nitrogen, an amide oxygen, and two acetate oxygen atoms) from one ligand molecule and an acetate oxygen atom from a neighboring zinc chelate. The zinc atoms are linked by Zn-O-C-O-Zn bonds and form a onedimensional array. The manganese complex crystallized in the orthorhombic space group Pccn with a = 16.325(1) Á, b = 17.468(1) Á, c = 15.144(1) Á, and Z = 4. The coordination geometry around the manganese atom is a highly distorted trigonal prism with five donor atoms from a ligand molecule and an oxygen atom from a water molecule. The formation constants of the ML species of Ni2+ and Cu2+ with (12edtaen)2" are significantly higher than those of the corresponding complexes with (13edtapn)2_. The MLH-2 species of Co2+, Ni2+, and Cu2+ formed with (13edtapn)2_ in the basic region have greater formation constants than the corresponding MLH-i species. The solution electronic spectra of the MLH-2 species of these complexes are quite different from those of the corresponding ML species, indicating that conversion of coordination geometry occurs as a result of deprotonation of amide nitrogen atoms. This conversion has been confirmed by an electron spin echo envelope modulation experiment for the Cu2+ complex. No significant spectral changes are observed with the M(12edtaen) complexes. In these complexes the mixed-ligand complexes, M(12edtaen)(OH)" ( = 1 or 2), are formed in the basic region, and the complexes with = 2 are much less stable than the corresponding complexes with = 1. These large differences in the properties of the metal complexes of the two macrocyclic ligands are caused by a difference of only one -CH2group in the ligand ring system.

C-Br bond activation followed by a C-C coupling reaction of the 2-bromo-pyridyl unit of [1-phenyl-2-(6-bromopyridin-2-yl)-benzoimidazole] was performed by Pd(CH(2)CMe(2)-o-C(6)H(4))(η(4)-COD). Two new seven membered palladacycles were obtained. A combined experimental and theoretical DFT study elucidates the mechanism for this reaction.