Cobalt complexes of tetradentate, bipyridine-based macrocycles: their structures, properties and photocatalytic proton reduction.

Complexes with purely pyridine-based macrocycles are rarely studied in photo(electro)catalysis. We synthesized and investigated macrocycles, in which two 2,2'-bipyridine (bpy) units are linked twice by two cyano-methylene groups, to yield the basic tetradentate, bipyridine based ligand framework (pyr). The protons in the bridges were substituted to obtain derivatives with one (pyr-alk) or two (pyr-alk2) alkyl-chains, respectively. We present the crystal structures of the mono-pentylated and the cis-dibutylated ligands. The corresponding Co(II) complexes [Co(II)(OH2)2(pyr)], [Co(II)Br(HOMe)(pyr-bu)], [Co(II)Br2(cis-pyr-bu2)] and [Co(II)Br2(trans-pyr-bu2)] were prepared, their physico-chemical properties elucidated and their crystal structures determined. X-ray analyses revealed for the latter three complexes distorted octahedral coordination and a fairly planar {Co(II)(pyr)} macrocyclic scaffold. The axial bromides in [Co(II)Br(HOMe)(pyr-bu)], [Co(II)Br2(cis-pyr-bu2)] and [Co(II)Br2(trans-pyr-bu2)] are weakly bound and dissociate upon dissolution in water. While the alkylated complexes are paramagnetic and feature Co(II) d(7) high spin configurations, the unsubstituted complex [Co(II)(OH2)2(pyr)] displays a rare Co(II) low spin configuration. The electronic ground states of [Co(II)Br2(cis-pyr-bu2)] and [Co(II)Br2(trans-pyr-bu2)] are similar, as evident from the almost identical UV/vis spectra. Electrochemical analyses show redox-non-innocent ligand frameworks. All complexes are highly robust and efficient H(+) reducing catalysts. In the presence of [Ru(bpy)3]Cl2 as a photosensitizer and TCEP/NaHasc as a sacrificial electron donor and shuttle, turnover numbers (TONs, H2/Co) up to 22 000 were achieved.

2.4 A crystal structure of an oxaliplatin 1,2-d(GpG) intrastrand cross-link in a DNA dodecamer duplex.

(1R,2R-Diaminocyclohexane)oxalatoplatinum(II) (oxaliplatin) is a third-generation platinum anticancer compound that produces the same type of inter- and intrastrand DNA cross-links as cisplatin. In combination with 5-fluorouracil, oxaliplatin has been recently approved in Europe, Asia, and Latin America for the treatment of metastatic colorectal cancer. We present here the crystal structure of an oxaliplatin adduct of a DNA dodecanucleotide duplex having the same sequence as that previously reported for cisplatin (Takahara, P. M.; Rosenzweig, A. C.; Frederick, C. A.; Lippard, S. J. Nature 1995, 377, 649-652). Pt-MAD data were used to solve this first X-ray structure of a platinated DNA duplex derived from an active platinum anticancer drug other than cisplatin. The overall geometry and crystal packing of the complex, refined to 2.4 A resolution, are similar to those of the cisplatin structure, despite the fact that the two molecules crystallize in different space groups. The platinum atom of the [Pt(R,R-DACH)](2+) moiety forms a 1,2-intrastrand cross-link between two adjacent guanosine residues in the sequence 5'-d(CCTCTGGTCTCC), bending the double helix by approximately 30 degrees toward the major groove. Both end-to-end and end-to-groove packing interactions occur in the crystal lattice. The latter is positioned in the minor groove opposite the platinum cross-link. A novel feature of the present structure is the presence of a hydrogen bond between the pseudoequatorial NH hydrogen atom of the (R,R)-DACH ligand and the O6 atom of the 3'-G of the platinated d(GpG) lesion. This finding provides structural evidence for the importance of chirality in mediating the interaction between oxaliplatin and duplex DNA, calibrating previously published models used to explain the reactivity of enantiomerically pure vicinal diamine platinum complexes with DNA in solution. It also provides a new kind of chiral recognition between an enantiomerically pure metal complex and the DNA double helix.

Fluorescent sensors for Zn(2+) based on a fluorescein platform: synthesis, properties and intracellular distribution.

Two new fluorescent sensors for Zn(2+) that utilize fluorescein as a reporting group, Zinpyr-1 and Zinpyr-2, have been synthesized and characterized. Zinpyr-1 is prepared in one step via a Mannich reaction, and Zinpyr-2 is obtained in a multistep synthesis that utilizes 4',5'-fluorescein dicarboxaldehyde as a key intermediate. Both Zinpyr sensors have excitation and emission wavelengths in the visible range ( approximately 500 nm), dissociation constants (K(d1)) for Zn(2+) of <1 nM, quantum yields approaching unity (Phi = approximately 0.9), and cell permeability, making them well-suited for intracellular applications. A 3- to 5-fold fluorescent enhancement is observed under simulated physiological conditions corresponding to the binding of the Zn(2+) cation to the sensor, which inhibits a photoinduced electron transfer (PET) quenching pathway. The X-ray crystal structure of a 2:1 Zn(2+):Zinpyr-1 complex has also been solved, and is the first structurally characterized example of a complex of fluorescein substituted with metal binding ligands.

Synthesis and spectroscopic studies of non-heme diiron(III) species with a terminal hydroperoxide ligand: models for hemerythrin.

Two compounds, [Fe2(mu-OH)(mu-Ph4DBA)(TMEDA)2(OTf)] (4) and [Fe2(mu-OH)(mu-Ph4DBA)(DPE)2(OTf)] (7), where Ph4DBA(2-) is the dinucleating bis(carboxylate) ligand dibenzofuran-4,6-bis(diphenylacetate), have been prepared as synthetic models for the dioxygen-binding non-heme diiron protein hemerythrin (Hr). X-ray crystallography reveals that, in the solid state, these compounds contain the asymmetric coordination environment found at the diiron center in the reduced form of the protein, deoxyHr. Mössbauer spectra of the models (4, delta = 1.21(2), DeltaE(Q) = 2.87(2) mm s(-1); 7, delta(av) = 1.23(1), DeltaE(Qav) = 2.79(1) mm s(-1)) and deoxyHr (delta = 1.19, DeltaE(Q) = 2.81 mm s(-1)) are also in good agreement. Oxygenation of the diiron(II) complexes dissolved in CH2Cl2 containing 3 equiv of N-MeIm (4) or neat EtCN (7) at -78 degrees C affords a red-orange solution with optical bands at 336 nm (7300 M(-1) cm(-1)) and 470 nm (2600 M(-1) cm(-1)) for 4 and at 334 nm (6400 M(-1) cm(-1)) and 484 nm (2350 M(-1) cm(-1)) for 7. These spectra are remarkably similar to that of oxyHr, 330 nm (6800 M(-1) cm(-1)) and 500 nm (2200 M(-1) cm(-1)). The electron paramagnetic resonance (EPR) spectrum of the cryoreduced, mixed-valence dioxygen adduct of 7 displays properties consistent with a (mu-oxo)diiron(II,III) core. An investigation of 7 and its dioxygen-bound adduct by extended X-ray absorption fine structure (EXAFS) spectroscopy indicates that the oxidized species contains a (mu-oxo)diiron(III) core with iron-ligand distances in agreement with those expected for oxide, carboxylate, and amine/hydroperoxide donor atoms. The analogous cobalt complex [Co2(mu-OH)(mu-Ph4DBA)(TMEDA)2(OTf)] (6) was synthesized and structurally characterized, but it was unreactive toward dioxygen.

Pentacoordinate cobalt(III) thiolate and nitrosyl tropocoronand compounds.

Reaction of [Co(TC-n,m)]+ with (Me4N)(SC6F5), where (TC-n,m) is a tropocoronand with n and m linker chain methylene groups, yielded the thiolate complexes [Co(SC6F5)(TC-3,3)] (1a), and [Co(SC6F5)(TC-4,4)] (2a), which were structurally characterized. Use of more electron-releasing thiolates afforded the [Co(TC-n,m)] reduction product and the corresponding disulfide. The bent nitrosyl complexes [Co(NO)(TC-3,3)] (1b) and [Co(NO)(TC-4,4)] (2b) were synthesized from [Co(TC-n,m)] and NO and their structures were also determined. Compounds 1a and 1b have square-pyramidal geometry like all other structurally characterized [MX(TC-3,3)] complexes. Compounds 2a and 2b have trigonal-bipyramidal stereochemistry, formerly rare for Co(III). Although 1a, 1b, and 2a are paramagnetic, 2b is diamagnetic due to the strong antibonding pi-interaction between the metal and NO pi* orbitals. In the presence of excess NO, [Co(TC-4,4)] exhibited novel reactivity in which a putative Co(N2) adduct formed.

Intermediate in beta-lactam hydrolysis catalyzed by a dinuclear zinc(II) complex: relevance to the mechanism of metallo-beta-lactamase.

Inactivation of beta-lactam antibiotics by metallo-beta-lactamase enzymes is a well-recognized pathway of antibiotic resistance in bacteria. As part of extensive mechanistic studies, the hydrolysis of a beta-lactam substrate nitrocefin (1) catalyzed by dinuclear zinc(II) model complexes was investigated in nonaqueous solutions. The initial step involves monodentate coordination of the nitrocefin carboxylate group to the dizinc center. The coordinated substrate is then attacked intramolecularly by the bridging hydroxide to give a novel intermediate (2') characterized by its prominent absorbance maximum at 640 nm, which affords a blue color. The NMR and IR spectroscopic data of 2' are consistent with it being zinc(II)-bound N-deprotonated hydrolyzed nitrocefin that forms from the tetrahedral intermediate upon C-N bond cleavage. Protonation of the leaving group is the rate-limiting step in DMSO solution and occurs after the C-N bond-breaking step. Addition of strong acids results in rapid conversion of 2' into hydrolyzed nitrocefin (3). The latter can be converted back to the blue species (2') upon addition of base. The low pK(a) value for the amino group in hydrolyzed nitrocefin is explained by its involvement in extended conjugation and by coordination to zinc(II). The blue intermediate (2') in the model system resembles well that in the enzymatic system, judging by its optical properties. The greater stability of the intermediate in the model, however, allowed its characterization by (13)C NMR and infrared, as well as electronic, spectroscopy.

Aminotroponiminates as ligands for potential metal-based nitric oxide sensors.

A family of new fluorescently labeled ligands, HRDATI, was prepared to develop transition-metal-based NO sensing strategies. The ligands are composed of aminotroponiminates (ATIs) with a dansyl fluorophore on one of the imine nitrogen atoms and an alkyl substituent, either i-Pr (8), t-Bu (9), or Bz (10), on the other. Bis(chelate) Co2+ ([Co(i-PrDATI)2] (12), [Co(t-BuDATI)2] (14), [Co(BzDATI)2] (15)) and Zn2+ ([Zn(i-PrDATI)2] (13)) complexes were prepared and characterized by X-ray crystallography. The bis(ATI) complex [Co(i-Pr2ATI)2] (11) was also prepared and its X-ray crystal structure determined. Cyclic voltammetry reveals reversible redox waves at -2.57 and -0.045 V (vs Cp2Fe/Cp2Fe+) in THF for the Co2+/Co+ and Co3+/Co2+ couples, respectively, of 11. Only a Co2+/Co+ wave at -2.09 V is observed for 12. When excited at 350 nm, the HRDATI ligands and the diamagnetic Zn2+ complex 13 fluoresce around 500 nm, whereas the paramagnetic Co2+ complexes quench the fluorescence. These air-stable cobalt compounds react with nitric oxide to dissociate a DATI ligand and form neutral dinitrosyl complexes, [Co(NO)2(RDATI)]. The release of the fluorophore-containing ligand is accompanied by an increase in fluorescence intensity, thus providing a strategy for fluorescent NO sensing. Linking two DATI moieties via a tetramethylene chain affords the ligand H2DATI-4 (18). The Co2+ complex [Co(DATI-4)] (19) reacts more readily with NO than the bis(DATI) compounds and also displays an increase in fluorescence intensity upon NO binding.

X-Ray Structure of a Heterochiral, Sulfoximine-Stabilized Dilithiomethane Derivative.

A distorted Li(6)O octahedron in the center and four geminal dilithiated sulfoximine units characterize a tetrameric aggregate of the chiral sulfoximine-stabilized dilithiomethane derivative 3, a previously unknown reaction intermediate in asymmetric dianion chemistry. A comparison with the crystal structure of the monolithiated parent 2, formed by the treatment of 1 with nBuLi, allows a rationalization of the second lithiation.