Dedicated to Professor M. Frederick Hawthorne on the occasion of his 75th birthdayThe application of electrophilic late-transition-metal complexes in catalysis has enjoyed widespread success in recent years. [1][2][3][4][5][6] We have been investigating electrophilic platinum complexes for catalysis and hydrocarbon CÀH bond activation [7,8] and recently reported a simple strategy for obtaining unsaturated electrophilic metal centers by addition of bulky bis(N-arylamino)phosphenium cations, easily derived from bis(N-aryl)diimines.

We report derivatives of gallium(III) tris(pentafluorophenyl)corrole, 1 [Ga(tpfc)], with either sulfonic (2) or carboxylic acids (3, 4) as macrocyclic ring substituents: the aminocaproate derivative, 3 [Ga(ACtpfc)], demonstrated high cytotoxic activity against all NCI60 cell lines derived from nine tumor types and confirmed very high toxicity against melanoma cells, specifically the LOX IMVI and SK-MEL-28 cell lines. The toxicities of 1, 2, 3, and 4 [Ga(3-ctpfc)] toward prostate (DU-145), melanoma (SK-MEL-28), breast (MDA-MB-231), and ovarian (OVCAR-3) cancer cells revealed a dependence on the ring substituent: IC 50 values ranged from 4.8 to >200 μM; and they correlated with the rates of uptake, extent of intracellular accumulation, and lipophilicity. Carboxylated corroles 3 and 4, which exhibited about 10-fold lower IC 50 values (<20 μM) relative to previous analogs against all four cancer cell lines, displayed high efficacy (E max = 0). Confocal fluorescence imaging revealed facile uptake of functionalized gallium corroles by all human cancer cells that followed the order: 4 >> 3 > 2 >> 1 (intracellular accumulation of gallium corroles was fastest in melanoma cells). We conclude that carboxylated gallium corroles are promising chemotherapeutics with the advantage that they also can be used for tumor imaging.

After a brief review of the use of photochemical triggers and heme metal substitution to probe the folding dynamics of cytochrome c, we present new results on the photophysics and photochemistry of folded and unfolded states of the zinc-substituted protein (Zn-cyt c). Our measurements of Zn-cyt c triplet state decay kinetics reveal a systematic isotope effect on lifetimes: the decay in the folded protein (tau(H)2(O) approximately 10 ms) is only modestly affected by isotopically substituted buffers (k(H)2(O)/k(D)2(O) = 1.2), whereas a reduced triplet lifetime (approximately 1.3 ms) and greater isotope effect (1.4) were found for the chemically denatured, fully unfolded protein. The shortest lifetime (0.1-0.4 ms) and greatest isotope effect (1.5) were found for a fully exposed model compound, zinc-substituted N-acetyl-microperoxidase-8 (ZnAcMP8), implying that the unfolded protein provides some protection to the Zn-porphyrin group even under fully denaturing conditions. Further evidence for partial structure in unfolded Zn-cyt c comes from bimolecular quenching experiments using Ru(NH(3))(6)(3+) as an external Zn-porphyrin triplet state quencher. In the presence of quencher, partially unfolded protein at midpoint guanidinium chloride (GdmCl) and urea concentrations exhibits biphasic triplet decay kinetics, a fast component corresponding to an extended, solvent-exposed state (6.6 x 10(8) M(-1) s(-1) in GdmCl, 6.3 x 10(8) M(-1) s(-1) in urea) and a slow component attributable to a compact, relatively solvent-inaccessible, state (5.9 x 10(7) M(-1) s(-1) in GdmCl, 8.6 x 10(6) M(-1) s(-1) in urea). The variation in Zn-porphyrin solvation for the compact states in the two denaturants reveals that the cofactor in the partially unfolded protein is better protected in urea solutions.

Dedicated to Professor M. Frederick Hawthorne on the occasion of his 75th birthdayThe application of electrophilic late-transition-metal complexes in catalysis has enjoyed widespread success in recent years. [1][2][3][4][5][6] We have been investigating electrophilic platinum complexes for catalysis and hydrocarbon CÀH bond activation [7,8] and recently reported a simple strategy for obtaining unsaturated electrophilic metal centers by addition of bulky bis(N-arylamino)phosphenium cations, easily derived from bis(N-aryl)diimines.

Two new Ru-based metathesis catalysts, 3 and 4, have been synthesized for the purpose of comparing their catalytic properties to those of their cis-selective nitrate analogues, 1 and 2. Although catalysts 3 and 4 exhibited slower initiation rates than 1 and 2, they maintained high cis-selectivity in homodimerization and ring-opening metathesis polymerization reactions. Furthermore, the nitrite catalysts displayed higher cis-selectivity than 2 for ring-opening metathesis polymerizations, and 4 delivered higher yields of polymer.