We report the synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2'-bipyridine rhenium tricarbonyl complexes. The study was promoted in order to...
The reaction of rhenium α-diimine (N-N) tricarbonyl complexes with nitrosonium tetrafluoroborate yields the corresponding dicarbonyl-nitrosyl [Re(CO)2(NO)(N-N)X]+ species (where X = halide). The complexes, accessible in a single step in good yield, are structurally nearly identical higher charge congeners of the tricarbonyl molecules. Substitution chemistry aimed at the realization of equivalent dicationic species (intended for applications as potential antimicrobial agents), revealed that the reactivity of metal ion in [Re(CO)2(NO)(N-N)X]+ is that of a hard Re acid, probably due to the stronger π-acceptor properties of NO+ as compared to those of CO. The metal ion thus shows great affinity for π-basic ligands, which are consequently difficult to replace by, e.g., σ-donor or weak π-acids like pyridine. Attempts of direct nitrosylation of α-diimine fac-[Re(CO)3]+ complexes bearing π-basic OR-type ligands gave the [Re(CO)2(NO)(N-N)(BF4)][BF4] salt as the only product in good yield, featuring a stable Re-FBF3 bond. The solid state crystal structure of nearly all molecules presented could be elucidated. A fundamental consequence of the chemistry of [Re(CO)2(NO)(N-N)X]+ complexes, it that the same can be photo-activated towards CO release and represent an entirely new class of photoCORMs.
The reaction of rhenium a-diimine (N-N) tricarbonyl complexes with nitrosonium tetrafluoroborate yields the corresponding dicarbonyl-nitrosyl [Re(CO)2(NO)(N-N)X]+ species (where X = halide). The complexes, accessible in a single step in good yied, are structurally nearly identical higher charge congeners of the tricarbonyl molecules. Substitution chemistry aimed at the realization of equivalent dicationic species (intended for applications as potential antimicrobial agents), revealed that the reactivity of metal ion in [Re(CO)2(NO)(N-N)X]+ is closer to that of a harder Re(III) acid, probably due to the stronger p-acceptor properties of NO+ as compared to those of CO. The metal ion thus shows great affinity for p-basic ligands, which are consequently difficult to replace by e.g. s-donor or week p-acids like pyridine. Attempts of direct nitrosylation of a-diimine fac-[Re(CO)3]+ complexes bearing p-basic OR-type ligands gave the [Re(CO)2(NO)(N-N)(BF4)][BF4] salt, as the only product in good yield, featuring a stable Re-F-BF3 bond. The solid state crystal structure of nearly all molecules presented could be elucidated. A fundamental consequence of the chemistry of [Re(CO)2(NO)(N-N)X]+ complexes, it that the same can be photo-activated towards CO release and represent an entirely new class of photoCORMs.
We report the synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2'-bipyridine rhenium tricarbonyl complexes. The study was promoted in order to understand if the presence and position of a reactive halomethyl substituent on the diimine ligand system of fac-[Re(CO)3]+ species may be a key molecular feature for the design of active and non-toxic anticancer agents. Only compounds potentially able of ligand-based alkylating reactions show significant antiproliferative activity against colorectal and pancreatic cell lines. The anticancer potency of the species, does not correlate with the hydrolysis rate or rate of reaction of the coordinated 5- and 6-(halomethyl)-2,2'-bipyridine with the amino acid lysine. Of the new species presented in this study, one compound (5-(chloromethyl)-2,2'-bipyridine derivative) shows significant inhibition of pancreatic tumour growth in vivo in zebrafish-Panc-1 xenografts. The complex is noticeably effective at 8 uM concentration, lower than its in vitro IC50 values, being also capable of inhibiting in vivo cancer cells dissemination.
The reaction of rhenium α-diimine (N-N) tricarbonyl complexes with nitrosonium tetrafluoroborate yields the corresponding dicarbonyl-nitrosyl [Re(CO)2(NO)(N-N)X] + species (where X = halide). The complexes, accessible in a single step in good yied, are structurally nearly identical higher charge congeners of the tricarbonyl molecules. Substitution chemistry aimed at the realization of equivalent dicationic species (intended for applications as potential antimicrobial agents), revealed that the reactivity of metal ion in [Re(CO)2(NO)(N-N)X] + is closer to that of a harder Re(III) acid, probably due to the stronger πacceptor properties of NO + as compared to those of CO. The metal ion thus shows great affinity for π-basic ligands, which are consequently difficult to replace by e.g. σ-donor or week π-acids like pyridine. Attempts of direct nitrosylation of αdiimine fac-[Re(CO)3] + complexes bearing π-basic OR-type ligands gave the [Re(CO)2(NO)(N-N)(BF4)][BF4] salt, as the only product in good yield, featuring a stable Re-F-BF3 bond. The solid state crystal structure of nearly all molecules presented could be elucidated. A fundamental consequence of the chemistry of [Re(CO)2(NO)(N-N)X] + complexes, it that the same can be photo-activated towards CO release and represent an entirely new class of photoCORMs.
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