Colchicine was derivatized at C7 with p-alkoxyacetophenone and conjugated to cobalamin (vitamin B(12)) through an acid-labile hydrazone linker. The cobalamin moiety leads to preferential uptake of the cobalamin-colchicine prodrug by cancer cells, whereupon the hydrazone linker undergoes hydrolysis in the lysosome to unmask colchicine, which acts as a potent cytotoxin by stabilizing microtubules and causing cell death. The bioconjugate is stable in cell culture media and at neutral pH but undergoes hydrolysis with a half-life of 138 min at pH 4.5. The colchicine-cobalamin bioconjugate exhibits nanomolar LC(50) values against breast, brain, and melanoma cancer cell lines in culture. Attachment of colchicine to cobalamin is expected to increase the therapeutic index of the drug by limiting the side effects caused by the current nonselective administration of tubulin-targeted chemotherapeutic drugs.

The crystal structures of [MnTPP]{Ni[S2C2H(CN)]2} [MnTPP = (meso-tetraphenylporphinato)manganese(III)] and [MnTPP]{Ni[S2C2(CN)2]2} have been determined. These salts possess trans-mu-coordination of S = 1/2 {Ni[S2C2H(CN)]2}*- and {Ni[S(2)C(2)(CN)(2)](2)}*- to Mn(III) and form parallel 1-D coordination polymer chains exhibiting nu(CN) at 2210 and 2200 and 2220 and 2212 cm(-1), respectively. The bis(dithiolato) monoanions are planar and bridge two cations with MnN distances of 2.339(16), and 2.394(3) A, respectively, which are comparable to related MnN distances observed for [MnTPP][TCNE].x(solvates). In addition, [MnTP'P]{Ni[S2C2(CN)2]2} {H2TP'P = meso-tetrakis[3,5-di-tert-butyl-4-hydroxyphenyl)porphyrin] and [MnTP'P(OH2)]{Ni[S2C2(CN)2]2} were prepared. The latter forms isolated paramagnetic ions. The room-temperature values of chiT for 1-D [MnTPP]{Ni[S2C2H(CN)]2}, [MnTPP]{Ni[S2C2(CN)2]2}, and [MnTP'P]{Ni[S2C2(CN)2]2} are 2.55, 3.28, and 2.86 emu K/mol, respectively. Susceptibility (chi) measurements between 2 and 300 K reveal weak antiferromagnetic interactions with theta= -5.9 and -0.2 K for [MnTPP]{Ni[S(2)C(2)H(CN)](2)} and [MnTPP]{Ni[S2C2(CN)2]2}, respectively, and stronger antiferromagnetic coupling of -50 K for [MnTP'P]{Ni[S2C2(CN)2]2} from fits of chi(T) to the Curie-Weiss law. The 1-D intrachain coupling, J(intra), of [MnTPP]{Ni[S2C2H(CN)]2} and [MnTPP]{Ni[S2C2(CN)2]2} was determined from modeling chiT(T) by the Seiden expression (H = -2JSi.Sj) with J/kB = -8.00 K (-5.55 cm(-1); -0.65 meV) for [MnTPP]{Ni[S2C2H(CN)]2}, J/kB = -3.00 K (-2.08 cm(-1); -0.25 meV) for [MnTP'P]{Ni[S2C2(CN)2]2}, and J/kB = -122 K (-85 cm(-1)) for [MnTP'P]{Ni[S2C2(CN)2]2}. These observed negative J(intra)/kB values are indicative of antiferromagnetic coupling. These materials order as ferrimagnets at 5.5, 2.3, and 8.0 K, for [MnTPP]{Ni[S2C2H(CN)]2}, [MnTPP]{Ni[S2C2(CN)2]2}, and [MnTP'P]{Ni[S2C2(CN)2]2}, respectively, based upon the temperature at which maximum in the 10 Hz chi'(T) data occurs. [MnTP'P]{Ni[S2C2(CN)2]2} has a coercivity of 17,700 Oe and remanent magnetizations of 7250 emu Oe/mol at 2 K and 17 Oe and 850 emu Oe/mol at 5 K; hence, upon cooling it goes from being a soft magnet to being a very hard magnet.