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To ascertain the bioinorganic chemistry of metals conjugated with quinones, the complexes [Ag(ATV)(PPh 3 ) 2 ] ( 1 ), [Au(ATV)(PPh 3 )]·2H 2 O ( 2 ), and [Cu(ATV)(PPh 3 ) 2 ] ( 3 ) were synthesized by the coordination of the antimalarial naphthoquinone atovaquone (ATV) to the starting materials [Ag(PPh 3)2 ]NO 3 , [Au(PPh 3 )Cl], and [Cu(PPh 3 ) 2 NO 3 ], respectively. These complexes were characterized by analytical and spectroscopical techniques. X-ray diffraction of single crystals precisely confirmed the coordination mode of ATV to the metals, which was monodentate or bidentate, depending on the metal center. Both coordination modes showed high stability in the solid state and in solution. All three complexes showed negative log D values at pH 5, but at pH 7.4, while complex 2 continued to have a negative log D value, complexes 1 and 3 displayed positive values, indicating a more hydrophilic character. ATV and complexes 1 - 3 could bind to ferriprotoporphyrin IX (FePPIX); however, only complexes 1 - 3 could inhibit β-hematin crystal formation. Phenotype-based activity revealed that all three metal complexes are able to inhibit the growth of P. falciparum with potency and selectivity comparable to those of ATV, while the starting materials lack this activity. The outcomes of this chemical design may provide significant insights into structure-activity relationships for the development of new antimalarial agents.

Twelve tri( N -carbazolyl)phosphine gold(I) complexes, bearing both protonated and deuterated aryl phosphorous triamide-type ligands, have been synthesized and characterized. An elusive Au-H(D) interaction between the H(D) atoms of the tri( N -carbazolyl)phosphine ligand at the H-1(D-1) position of the carbazolyl ring and the central gold atom was observed. Complexes 5(H) / 5(D) bearing the dibrominated tri( N -carbazolyl)phosphine ligand exhibit isotopic polymorphism, in which two dramatically different crystal-packing modes between the protonated and deuterated forms occur. The catalytic potential of these complexes has been showcased in the gold(I)-catalyzed glycosylation with glycosyl o -alkynylbenzoates as donors, with TON being up to 27 000.

N-Triphos derivatives (NP 3 R , R = alkyl, aryl) and asymmetric variants (NP 2 R X R' , R' = alkyl, aryl, X = OH, NR 2 , NRR') are an underexplored class of tuneable, tripodal ligands in relation to the coordination chemistry of Re and Tc for biomedical applications. Mixed-ligand approaches are a flexible synthetic route to obtain Tc complexes of differing core structures and physicochemical properties. Reaction of the NP 3 Ph ligand with the Re(V) oxo precursor [ReOCl 3 (PPh 3 ) 2 ] generated the bidentate complex [ReOCl 3 (κ 2 -NP 2 Ph OH Ar )], which possesses an unusual AA'BB'XX' spin system with a characteristic second-order NMR lineshape that is sensitive to the bi- or tridentate nature of the coordinating diphosphine unit. The use of the asymmetric NP 2 Ph OH Ar ligand resulted in the formation of both bidentate and tridentate products depending on the presence of base. The tridentate Re(V) complex [ReOCl 2 (κ 3 -NP 2 Ph O Ar )] has provided the basis of a new reactive "metal-fragment" for further functionalization in [3 + 2] mixed-ligand complexes. The synthesis of [3 + 2] complexes with catechol-based π-donors could also be achieved under one-pot, single-step conditions from Re(V) oxo precursors. Analogous complexes can also be synthesized from suitable 99 Tc(V) precursors, and these complexes have been shown to exhibit highly similar structural properties through spectroscopic and chromatographic analysis. However, a tendency for the {M V O} 3+ core to undergo hydrolysis to the {M V O 2 } + core has been observed both in the case of M = Re and markedly for M = 99 Tc complexes. It is likely that controlling this pathway will be critical to the generation of further stable Tc(V) derivatives.

The fac -[M(CO) 3 (PyA)(P)] and cis-trans -[M(CO) 2 (PyA)(P) 2 ] neutral complexes (M is Re or 99m Tc), based on the mixed ligand strategy with pyrazine-2-carboxylic acid (PyAH) as the bidentate N,O and triphenylphosphine as the monodentate P ligand, are presented. Through the employment of the anhydride of pyrazine-2,3-dicarboxylic acid (PyDA), the PyAH scaffold was conveniently derivatized with the model bioactive amine 1-(2-methoxyphenyl)piperazine, the active part of the 5-HT 1A antagonist WAY100635. Reaction of either PyAH or the pharmacophore-bearing PyAH ligand (L 1 H) with fac- [M(CO) 3 ] + core in water yielded the intermediate fac -[M(CO) 3 (PyA)(H 2 O)] complexes. The labile aqua ligand was easily replaced by PPh 3 to yield the fac -[Re(CO) 3 (PyA)(PPh 3 )] complexes, while in toluene under reflux, the cis-trans -[Re(CO) 2 (PyA)(PPh 3 ) 2 ] complexes were obtained. The latter complexes were alternatively obtained from mer -[Re(CO) 3 (PPh 3 ) 2 Cl] by refluxing with the PyA ligand in toluene. The analogous 99m Tc complexes were synthesized quantitatively, showing excellent stability in competition studies. The methodology described herein represents a practical procedure for the effective integration of the fac -[M(CO) 3 ] + core with amine-bearing biologically active compounds for diagnosis/therapy.

A series of activated vinyl azoles was hydrophosphinated in the presence of a chiral palladacycle catalyst under mild conditions to give enantioenriched phosphine azoles with moderate enantioselectivities and yields. The racemic phosphine azoles were transformed into eleven novel chelating phosphine-N-heterocyclic carbene (NHC) platinum complexes. The drug efficacies of nine selected phosphine-NHC platinum(II) chlorides in two cancer cell lines (MKN74 and MCF7) were evaluated, and two were found to exhibit activities comparable to that of cisplatin.

Ruthenium(II) complexes ( Ru1 - Ru5 ), with the general formula [Ru(N-S)(dppe) 2 ]PF 6 , bearing two 1,2- bis (diphenylphosphino)ethane (dppe) ligands and a series of mercapto ligands (N-S), have been developed. The combination of these ligands in the complexes endowed hydrophobic species with high cytotoxic activity against five cancer cell lines. For the A549 (lung) and MDA-MB-231 (breast) cancer cell lines, the IC 50 values of the complexes were 288- to 14-fold lower when compared to cisplatin. Furthermore, the complexes were selective for the A549 and MDA-MB-231 cancer cell lines compared to the MRC-5 nontumor cell line. The multitarget character of the complexes was investigated by using calf thymus DNA (CT DNA), human serum albumin, and human topoisomerase IB (hTopIB). The complexes potently inhibited hTopIB. In particular, complex [Ru(dmp)(dppe) 2 ]PF 6 ( Ru3 ), bearing the 4,6-diamino-2-mercaptopyrimidine (dmp) ligand, effectively inhibited hTopIB by acting on both the cleavage and religation steps of the catalytic cycle of this enzyme. Molecular docking showed that the Ru1 - Ru5 complexes have binding affinity by active sites on the hTopI and hTopI-DNA, mainly via π-alkyl and alkyl hydrophobic interactions, as well as through hydrogen bonds. Complex Ru3 displayed significant antitumor activity against murine melanoma in mouse xenograph models, but this complex did not damage DNA, as revealed by Ames and micronucleus tests.

A highly stable framework of an organic-inorganic hybrid indium phosphate ( NTOU-7 ) was synthesized under hydro(solvo)thermal conditions and structurally characterized by single-crystal X-ray diffraction and solid-state NMR spectroscopy. This is the first example of a post-transition-metal phosphate incorporating tetradentate organic molecules. The In atoms in the inorganic layers are coordinated by imidazole rings of the 1,2,4,5-tetrakis(imidazol-1-ylmethyl)benzene linkers to generate a new solid-state material. NTOU-7 showed high chemical stability and displayed excellent performance for both dye removal and ractopamine (RAC) detection, which are interesting environmental and biosensing applications. The sensitivity and ultralow limit of detection were 607.9 μA·μM·cm -2 and 2.74 × 10 -10 mol·L -1 (0.08 ppb), which meet the requirements stated by the Codex Alimentarius Commission (10 ppb RAC residue in beef and pork). The detection performance was confirmed by sensing spiked-in RAC in real pork samples. We also reported the synthesis, characterization, structural stability, dye removal, and sensing properties of NTOU-7 .

Low-toxic InP quantum dots (QDs) as an ideal candidate for Cd-based QDs have tremendous potential for next-generation commercial display and biological detection applications. However, the progress in biological detection is still far behind that of the Cd-based QDs. This is mainly because the InP-based QDs are of inferior stability and photoluminescence quantum yield (PL QY) in aqueous solution. Here, PL QY of 65% and excellent stability of InP/GaP/ZnS QD@SiO 2 nanoparticles have been successfully synthesized via a silica coating method. The containing thiol-capped hydrophobic InP/GaP/ZnS QDs were pre-silanized with waterless, ammonia-free hydrolysis tetraethyl orthosilicate, and subsequently, an outer silica shell was generated in the reverse microemulsion. The corresponding QD-based fluorescence-linked immunosorbent assay exhibits a high sensitivity of 0.9 ng mL -1 for C-reactive protein and the broad detection range of 1-1000 ng mL -1 , which was close to that of the state-of-the-art Cd-based QD@SiO 2 nanoparticles and had the highest sensitivity of Cd-free QDs so far. This work provides a very successful silica coating method for the containing thiol-capped hydrophobic QDs and the QDs highly sensitive to water and oxygen, and the obtained InP/GaP/ZnS QD@SiO 2 nanoparticles were considered as the robust, biocompatible, and promising Cd-free fluorescent labels for the further ultra-sensitive detection.

A series of silver(I) camphorsulfonato complexes containing various phosphine ligands having the stoichiometry [Ag(camphSO 3 )(PR 3 )] [PR 3 = PTA (1,3,5-triaza-7-phosphaadamantane), PASO 2 (2-thia-1,3,5-triaza-7-phosphaadamantane-2,2-dioxide), PPh 3 , PCy 3 , P(CH 2 CH 2 CN) 3 , PPyPh 2 , or P( o -tol) 3 ] were prepared and fully characterized by NMR spectroscopic methods and X-ray crystallography. Depending on the nature of the phosphine, a variety of different supramolecular structures, including dimers, macrocycles, and coordination polymers, were observed in the solid state. The in vitro antimicrobial activity in seven different pathogens ( Staphylococcus aureus , Escherichia coli , Klebsiella pneumoniae , Pseudomonas aeruginosa , Acinetobacter baumannii , Candida albicans , and Cryptococcus neoformans var. grubii ) as well as toxicity in human cells was also examined. While all compounds show some activity against the bacteria, they were especially active against the fungus C. neoformans . The most active and at the same time least toxic compound was found to be the water-soluble complex [Ag(camphSO 3 )(PTA) 2 ].

Reaction of [ReOCl 3 (PPh 3 ) 2 ] or [ReO 2 I(PPh 3 ) 2 ] with 2,2'-diphenylglycine (dpgH 2 ) in refluxing ethanol afforded the air-stable complex [ReO(dpgH)(dpg)(PPh 3 )] ( 1 ). Treatment of [ReO(OEt)I 2 (PPh 3 ) 2 ] with 1,2,3-triaza-7-phosphaadamantane (PTA) afforded the complex [ReO(OEt)I 2 (PTA) 2 ] ( 2 ). Reaction of [ReOI 2 (PTA) 3 ] with dpgH 2 led to the isolation of the complex [Re(NCPh 2 )I 2 (PTA) 3 ]·0.5EtOH ( 3 ·0.5EtOH). A similar reaction but using [ReOX 2 (PTA) 3 ] (X = Cl, Br) resulted in the analogous halide complexes [Re(NCPh 2 )Cl 2 (PTA) 3 ]·2EtOH ( 4 ·2EtOH) and [Re(NCPh 2 )(PTA) 3 Br 2 ]·1.6EtOH ( 5 ·1.6EtOH). Using benzilic acid (2,2'-diphenylglycolic acid, benzH) with 2 afforded the complex [ReO(benz) 2 (PTA)][PTAH]·EtOH ( 6 ·EtOH). The potential for the formation of complexes using radioisotopes with relatively short half-lives suitable for nuclear medicine applications by developing conditions for [Re(NCPh 2 )(dpg)I(PTA) 3 ] ( 7 )[ReO 4 ] - in a 4 h time scale was investigated. A procedure for the technetium analog of complex [Re(NCPh 2 )I 2 (PTA) 3 ] ( 3 ) from 99m Tc[TcO 4 ] - was then investigated. The molecular structures of 1 - 7 are reported; complexes 3 - 7 have been studied using in vitro cell assays (HeLa, HCT116, HT-29, and HEK 293) and were found to have IC 50 values in the range of 29-1858 μM.

New alkynylgold(I) with P(NMe 2 ) 3 (HMPT) phosphane complexes, [Au(C≡C-R)(HMPT)] (R= 4-Ph, 4-MePh, 4-OMe, 4-Br, 4-Cl, 2-py, and 3-py) have been synthesized and characterized, including X-ray studies of complexes with R= 4-OMe and 4-Br; additionally, their physicochemical properties and anticancer activity have been tested. Due to the great water solubility of the HMPT phosphane, all the complexes exhibit an optimal balance of hydrophilicity/lipophilicity. Also, all of these complexes are quite stable in physiological conditions and interact well enough with the transport protein BSA. All complexes exhibit a higher anticancer activity against Caco-2 cells than cisplatin, and some of them do not present cytotoxic activity against enterocyte-like differentiated cells. The selective complexes are proapoptotic drugs by the exposure of phosphatidylserine, results that are also confirmed in primary cultures from mouse colon tumors. Complexes with a halogen unit also arrest the cell cycle in G2/M phase. It is thought that maybe these apoptosis processes are promoted by the observed oxidative damage in the membrane lipids, as a consequence of the inhibition of the thioredoxin reductase enzyme. Based on our results, we conclude that five of our complexes are good candidates to be used in chemotherapy.

A series of alkynylgold(I) phosphine complexes containing methoxy-substituted cinnamide moieties (3a-3c and 4a-4c) have been synthesized and characterized. All of the synthesized complexes were evaluated for their cytotoxicity against three human cancer cell lines A549 (lung), D24 (melanoma), and HT1080 (fibrosarcoma) and the human embryonic kidney 293 cell line (Hek293T) as a proxy model for noncancer cells. Most of the synthesized compounds showed antiproliferative activity against cancer cell lines at low micromolar concentrations. Among these, complex 3c showed a broad spectrum of anticancer activity with IC 50 values in the range of 1.53-6.05 μM against all tested cancer lines. Complex 3c possessed 20 times higher cytotoxicity than the reference drug cisplatin against D24 melanoma cells and showed significant anticancer activity in 3D spheroidal models of melanoma cells. Mechanistic investigations of 3c activity indicate thioredoxin reductase inhibition through steric and hydrogen-bonding interactions, followed by the induction of oxidative stress and a mitochondrial pathway of cell death. Compound 3c also showed significant antiangiogenic properties in a transgenic zebrafish Tg(fli1a:EGFP) in vivo model.

Two series of neutral luminescent pentafluorophenyl cycloplatinated(II) complexes [Pt(C^N)(C 6 F 5 )L] [C^N = C-deprotonated 2-phenylpyridine (ppy; a), 2-(2,4-difluorophenylpyridine (dfppy; b)] incorporating dimethyl sulfoxide [L = DMSO for 1 (1a reported by us in ref (14) )] or biocompatible phosphine [L = PPh 2 C 6 H 4 COOH (dpbH; 2), PPh 2 C 6 H 4 CONHCH 2 COOMe (dpbGlyOMe; 3), P(C 6 H 4 SO 3 Na) 3 (TPPTS; 4)] ligands have been prepared and characterized and their optical properties studied. Their cytotoxic activities against tumor A549 (lung carcinoma), HeLa (cervix carcinoma), and nontumor NL-20 (lung epithelium) cell lines, as well as the ability to interact with DNA (plasmid pBR322), were evaluated. Complexes 2 exhibit higher cytotoxicity (IC 50 3.89-20.29 μM) than compounds 1 (9.03-20.50 μM), whereas the activities of complexes 3 and 4 are negligible. All cytotoxic complexes show low selective toxicities toward cancer cells. Interestingly, except 1a, these complexes do not show evidence of DNA intercalation. Along the same lines, fluorescence costaining with Hoechst (2,5'-bi-1 H-benzimidazole, 2'-(4-ethoxyphenyl)-5-(4-methyl-1-piperazinyl), a nuclear DNA stain) reveals that all complexes easily internalize, being mainly localized in the cytoplasm. In order to deepen the mechanism of biological action, the effect of the most cytotoxic complex 2b toward the dynamics of tubulin was explored. This complex displays tubulin depolymerization activity, exhibiting more potent inhibition of microtubule formation in A549 than in HeLa cells, in accordance with its higher antiproliferative activity (IC 50 6.98 vs 12.45 μM), placing this complex as a potential antitubulin agent.

Fifteen water-soluble rhenium compounds of the general formula [Re(CO) 3 (NN)(PR 3 )] + , where NN is a diimine ligand and PR 3 is 1,3,5-triaza-7-phosphaadamantane (PTA), tris(hydroxymethyl)phosphine (THP), or 1,4-diacetyl-1,3,7-triaza-5-phosphabicylco[3.3.1]nonane (DAPTA), were synthesized and characterized by multinuclear NMR spectroscopy, IR spectroscopy, and X-ray crystallography. The complexes bearing the THP and DAPTA ligands exhibit triplet-based luminescence in air-equilibrated aqueous solutions with quantum yields ranging from 3.4 to 11.5%. Furthermore, the THP and DAPTA complexes undergo photosubstitution of a CO ligand upon irradiation with 365 nm light with quantum yields ranging from 1.1 to 5.5% and sensitize the formation of 1 O 2 with quantum yields as high as 70%. In contrast, all of the complexes bearing the PTA ligand are nonemissive and do not undergo photosubstitution upon irradiation with 365 nm light. These compounds were evaluated as photoactivated anticancer agents in human cervical (HeLa), ovarian (A2780), and cisplatin-resistant ovarian (A2780CP70) cancer cell lines. All of the complexes bearing THP and DAPTA exhibited a cytotoxic response upon irradiation with minimal toxicity in the absence of light. Notably, the complex with DAPTA and 1,10-phenanthroline gave rise to an IC 50 value of 6 μM in HeLa cells upon irradiation, rendering it the most phototoxic compound in this library. The nature of the photoinduced cytotoxicity of this compound was explored in further detail. These data indicate that the phototoxic response may result from the release of both CO and the rhenium-containing photoproduct, as well as the production of 1 O 2 .

A series of copper(I)-phosphine polypyridyl complexes have been investigated as potential antitumor agents. The complexes [Cu(PPh 3 ) 2 dpq]NO 3 (2), [Cu(PPh 3 ) 2 dppz]NO 3 (3), [Cu(PPh 3 ) 2 dppa]NO 3 (4), and [Cu(PPh 3 ) 2 dppme]NO 3 (5) were synthesized by the reaction of [Cu(PPh 3 ) 2 NO 3 ] with the respective planar ligand under mild conditions. These copper complexes were fully characterized by elemental analysis, molar conductivity, FAB-MS, and NMR, UV-vis, and IR spectroscopies. Interactions between these copper(I)-phosphine polypyridyl complexes and DNA have been investigated using various spectroscopic techniques and analytical methods, such as UV-vis titrations, thermal denaturation, circular dichroism, viscosity measurements, gel electrophoresis, and competitive fluorescent intercalator displacement assays. The results of our studies suggest that these copper(I) complexes interact with DNA in an intercalative way. Furthermore, their high protein binding affinities toward human serum albumin were determined by fluorescence studies. Additionally, cytotoxicity analyses of all complexes against several tumor cell lines (human breast, MCF-7; human lung, A549; and human prostate, DU-145) and non-tumor cell lines (Chinese hamster lung, V79-4; and human lung, MRC-5) were performed. The results revealed that copper(I)-phosphine polypyridyl complexes are more cytotoxic than the corresponding planar ligand and also showed to be more active than cisplatin. A good correlation was observed between the cytostatic activity and lipophilicity of the copper(I) complexes studied here.

All elementary steps in the mechanism of Pd-catalyzed decarbonylation of hydrocinnamic acid through formation of a mixed anhydride species have been characterized through electronic structure calculations. Oxidative addition of the mixed anhydride to a singly or doubly ligated Pd is followed by decarbonylation, alkene formation, and catalyst regeneration. Metal-assisted deprotonation of the alkyl-Pd species by a coordinated carboxylate is predicted to be the rate-determining step; theory suggests that bulkier phosphine ligands (e.g., P(o-Tol)3) reduce the free energy of activation substantially, while variation of the auxiliary anhydride has little influence on efficiency.

Chiral molecules in nature are involved in many biological events; their selectivity and specificity make them of great interest for understanding the behavior of bioactive molecules, by providing information about the chiral discrimination. Inspired by these conformational properties, we present the design and synthesis of novel chiral platinum(II) complexes featuring phosphine and chloroquine ligands with the general formula [PtCl(P)2(CQ)]PF6 (where (P)2 = triphenylphosphine (PPh3) (5), 1,3-bis(diphenylphosphine)propane (dppp) (6), 1,4-bis(diphenylphosphine)butane (dppb) (7), 1,1'-bis(diphenylphosphine)ferrocene (dppf) (8), and CQ = chloroquine] and their precursors of the type [PtCl2(P)2] are described. The complexes were characterized by elemental analysis, absorption spectroscopy in the infrared and ultraviolet-visible (UV-vis) regions, multinuclear ((1)H, (13)C, (31)P, (15)N, and (195)Pt) NMR spectroscopy, cyclic voltammetry, and mass spectrometry (in the case of chloroquine complexes). The interactions of the new platinum-chloroquine complexes with both albumin (BSA), using fluorescence spectroscopy, and DNA, by four widely reported methods were also evaluated. These experiments showed that these Pt-CQ complexes interact strongly with DNA and have high affinities for BSA, in contrast to CQ and CQDP (chloroquine diphosphate), which interact weakly with these biomolecules. Additional assays were performed in order to investigate the cytotoxicity of the platinum complexes against two healthy cell lines (mouse fibroblasts (L929) and the Chinese hamster lung (V79-4)) and four tumor cell lines (human breast (MDA-MB-231 and MCF-7), human lung (A549), and human prostate (DU-145)). The results suggest that the Pt-CQ complexes are generally more cytotoxic than the free CQ, showing that they are promising as anticancer drugs.

The two MeCN ligands in [Ru(2-C6H4-2'-Py-κC,N)(Phen, trans-C)(MeCN)2]PF6 (1), both trans to a sp(2) hybridized N atom, cannot be substituted by any other ligand. In contrast, the isomerized derivative [Ru(2-C6H4-2'-Py-κC,N)(Phen, cis-C)(MeCN)2]PF6 (2), in which one MeCN ligand is now trans to the C atom of the phenyl ring orthometalated to Ru, leads to fast and quantitative substitution reactions with several monodentate ligands. With PPh3, 2 affords [Ru(2-C6H4-2'-Py-κC,N)(Phen, cis-C)(PPh3)(MeCN)]PF6 (3), in which PPh3 is trans to the C σ bound to Ru. Compound 3 is not kinetically stable, because, under thermodynamic control, it leads to 4, in which the PPh3 is trans to a N atom of the Phen ligand. Dimethylsulfoxide (DMSO) can also substitute a MeCN ligand in 2, leading to 5, in which DMSO is coordinated to Ru via its S atom trans to the N atom of the Phen ligand, the isomer under thermodynamic control being the only compound observed. We also found evidence for the fast to very fast substitution of MeCN in 2 by water or a chloride anion by studying the electronic spectra of 2 in the presence of water or NBu4Cl, respectively. An isomerization related to that observed between 3 and 4 is also found for the known monophosphine derivative [Ru(2-C6H4-2'-Py-κC,N)(PPh3, trans-C)(MeCN)3]PF6 (10), in which the PPh3 is located trans to the C of the cyclometalated 2-phenylpyridine, since, upon treatment by refluxing MeCN, it leads to its isomer 11, [Ru(2-C6H4-2'-Py-κC,N)(PPh3, cis-C)(MeCN)3]PF6. Further substitutions are also observed on 11, whereby N^N chelates (N^N = 2,2'-bipyridine and phenanthroline) substitute two MeCN ligands, affording [Ru(2-C6H4-2'-Py-κC,N)(PPh3, cis-C)(N^N)(MeCN)]PF6 (12a and 12b). Altogether, the behavior of the obtained complexes by ligand substitution reactions can be rationalized by an antisymbiotic effect on the Ru center, trans to the C atom of the cyclometalated unit, leading to compounds having the least nucleophilic ligand trans to C whenever an isomerization, involving either a monodentate or a bidentate ligand, is possible.

Diamagnetic iron chloro compounds [(P(Ph)2N(Ph)2)FeCp*Cl] [1Cl] and [(P(Cy)2N(Ph)2)FeCp*Cl] [2Cl] and the corresponding hydrido complexes [(P(Ph)2N(Ph)2)FeCp*H] [1H] and [(P(Cy)2N(Ph)2)FeCp*H] [2H] have been synthesized and characterized by NMR spectroscopy, electrochemical studies, electronic absorption, and (57)Fe Mössbauer spectroscopy (P(Ph)2N(Ph)2 = 1,3,5,7-tetraphenyl-1,5-diphospha-3,7-diazacyclooctane, P(Cy)2N(Ph)2 = 1,5-dicyclohexyl-3,7-diphenyl-1,5-diphospha-3,7-diazacyclooctane, Cp* = pentamethylcyclopentadienyl). Molecular structures of [2Cl], [1H], and [2H], derived from single-crystal X-ray diffraction, revealed that these compounds have a typical piano-stool geometry. The results show that the electronic properties of the hydrido complexes are strongly influenced by the substituents at the phosphorus donor atoms of the P(R)2N(Ph)2 ligand, whereas those of the chloro complexes are less affected. These results illustrate that the hydride is a strong-field ligand, as compared to chloride, and thus leads to a significant degree of covalent character of the iron hydride bonds. This is important in the context of possible catalytic intermediates of iron hydrido species, as proposed for the catalytic cycle of [FeFe] hydrogenases and other synthetic catalysts. Both hydrido compounds [1H] and [2H] show enhanced catalytic currents in cyclic voltammetry upon addition of the strong acid trifluoromethanesulfonimide [NHTf2] (pKa(MeCN) = 1.0). In contrast to the related complex [(P(tBu)N(Bn))2FeCp(C6F5)H], which was reported by Liu et al. (Nat. Chem. 2013, 5, 228-233) to be an electrocatalyst for hydrogen splitting, the here presented hydride complexes [1H] and [2H] show the tendency for electrocatalytic hydrogen production. Hence, the catalytic direction of this class of monoiron compounds can be reversed by specific ligand modifications.

The reduction of fac-[CrCl3(P(Ph)3N(Bn)3)], (1(Cl3)), (P(Ph)3N(Bn)3 = 1,5,9-tribenzyl-3,7,11-triphenyl-1,5,9-triaza-3,7,11-triphosphacyclododecane) with Mg in the presence of dmpe (dmpe = 1,2-bis(dimethylphosphino)ethane) affords the first example of a monodinitrogen Cr(0) complex, Cr(N2)(dmpe)(P(Ph)3N(Bn)3), (2(N2)), containing a pentaphosphine coordination environment. 2(N2) is supported by a unique facially coordinating 12-membered phosphorus macrocycle containing pendant amine groups in the second coordination sphere. Treatment of 2(N2) at -78 °C with 1 equiv of [H(OEt2)2][B(C6F5)4] results in protonation of the metal center, generating the seven-coordinate Cr(II)-N2 hydride complex, [Cr(H)(N2)(dmpe)(P(Ph)3N(Bn)3)][B(C6F5)4], [2(H)(N2)](+). Treatment of 2((15)N2) with excess triflic acid at -50 °C afforded a trace amount of (15)NH4(+) from the reduction of the coordinated (15)N2 ligand (electrons originate from Cr). Electronic structure calculations were employed to evaluate the pKa values of three protonated sites of 2(N2) (metal center, pendant amine, and N2 ligand) and were used to predict the thermodynamically preferred Cr-NxHy intermediates in the N2 reduction pathway for 2(N2) and the recently published complex trans-[Cr(N2)2(P(Ph)4N(Bn)4)] upon the addition of protons and electrons.

A reinvestigation of the treatment of [Fe(N2)(PP)2] (PP = depe, dmpe) with acid revealed no ammonium formation. Instead, rapid protonation at the metal center to give hydride complexes was observed. Treatment of [Fe(N2)(dmpe)2] with methylating agents such as methyl triflate or methyl tosylate resulted in methylation of the metal center to afford [FeMe(N2)(dmpe)2](+). Treatment of [Fe(N2)(dmpe)2] with trimethylsilyl triflate, however, resulted in reaction at dinitrogen affording NH4(+) on subsequent treatment with acid. The side-on bound hydrazine complex [Fe(N2H4)(dmpe)2](2+) and bis(ammonia) complex [Fe(NH3)2(dmpe)2](2+) were identified by (15)N NMR spectroscopy as other species formed in the reaction mixture.

An original copper(I) iodide cluster of novel geometry obtained by using a diphosphine ligand is reported and is formulated [Cu6I6(PPh2(CH2)3PPh2)3] (1). Interestingly, this sort of "eared cubane" cluster based on the [Cu6I6] inorganic core can be viewed as a combination of the two known [Cu4I4] units, namely, the cubane and the open-chair isomeric geometries. The synthesis, structural and photophysical characterisations, as well as theoretical study of this copper iodide along with the derived cubane (3) and open-chair (2) [Cu4I4(PPh3)4] forms, were investigated. A new polymorph of the cubane [Cu4I4(PPh3)4] cluster is indeed presented (3). The structural differences of the clusters were analyzed by solid-state nuclear magnetic resonance spectroscopy. Luminescence properties of the three clusters were studied in detail as a function of the temperature showing reversible luminescence thermochromism for 1 with an intense orange emission at room temperature. This behavior presents different feature compared to the cubane cluster and completely contrasts with the open isomer, which is almost nonemissive at room temperature. Indeed, the thermochromism of 1 differs by a concomitant increase of the two emission bands by lowering the temperature, in contrast to an equilibrium phenomenon for 3. The luminescence properties of 2 are very different by exhibiting only one single band when cooled. To rationalize the different optical properties observed, density functional theory calculations were performed for the three clusters giving straightforward explanation for the different luminescence thermochromism observed, which is attributed to different contributions of the ligands to the molecular orbitals. Comparison of 3 with its [Cu4I4(PPh3)4] cubane polymorphs highlights the sensibility of the emission properties to the cuprophilic interactions.

A number of monosubstituted n-(triphenylphosphonio)-7,8-dicarba-nido-undecaboranes (2a, n = 1; 2b, n = 3; 2c, n = 5; 2d, n = 9) were prepared via a cross-coupling reaction between the tetrabutylammonium iodo-7,8-dicarba-nido-undecaborates (1a-d) and PPh3 in the presence of a Pd(PPh3)4 catalyst. The substitution rate was found to depend on the iodine position in the carborane cage. Under similar conditions, the reaction of 5,6-diiodo- (3) and 9,11-diiodo-7,8-dicarba-nido-undecaborate (5) anions exclusively yielded the monosubstitution products 5-iodo-6-(triphenylphosphonio)-7,8-dicarba-nido-undecaborane (4) and 9-iodo-11-(triphenylphosphonio)-7,8-dicarba-nido-undecaborane (6), respectively. The reaction of tetrabutylammonium 6,9-diiodo-7,8-dicarba-nido-undecaborate (7) exclusively produced the phosphine substitution product in the open face of the nido-carborane, 6-iodo-9-triphenylphosphonio-7,8-dicarba-nido-undecaborane (8). The addition of a base (Cs2CO3, NaH) to the reactions of 3 and 5 with PPh3 afforded the corresponding bis(triphenylphosphonio)-7,8-dicarba-nido-undecaboranes, 9 and 10. Compound 10 was also prepared from 6 using the general procedure. The reaction of the triiodocarborane tetrabutylammonium 5,6,9-triiodo-7,8-dicarba-nido-undecaborate (11) with excess PPh3 in the presence of Cs2CO3 and Pd(PPh3)4 only produced neutral 5-iodo-6,9-bis(triphenylphosphonio)-7,8-dicarba-nido-undecaborane (12); no positively charged tris(phosphonio) species formed. The compositions of all prepared compounds were determined by multinuclear NMR spectroscopy and high-resolution mass spectrometry. The structures of compounds 2c, 6, 8, 9, and 12 were established by the X-ray diffraction analysis of single crystals.

A novel dicationic system containing a PN fragment has been synthesized and structurally characterized. According to the solid-state analysis and theoretical investigation, the dicationic iminophosphane resonance form is the most appropriate description for the dication. However, the contribution from the phosphorus mononitride resonance form is not negligible.

The coordination properties of isopropylxanthate (i-Pr-Tiox) and pyridine-2-thiolate (PyS) toward the [M(PS)2](+) moiety (M = Re and (99m)Tc; PS = phosphinothiolate) were investigated. Synthesis and full characterization of [Re(PS2)2(i-Pr-Tiox)] (Re1), [Re(PSiso)2(i-Pr-Tiox)] (Re2), [Re(PS2)2(PyS)] (Re3), and [Re(PSiso)2(PyS)] (Re4), where PS2 = 2-(diphenylphosphino)ethanethiolate and PSiso = 2-(diisopropylphosphino)ethanethiolate, and the structural X-ray analysis of complex Re3 were carried out. (99m)Tc analogues of complexes Re2 ((99m)Tc2) and Re4 ((99m)Tc4) were obtained in high radiochemical yield following a simple one-pot procedure. The chemical identity of the radiolabeled compounds was confirmed by chromatographic comparison with the corresponding rhenium complexes and by dual radio/UV HPLC analysis combined with ESI(+)-MS of (99g/99m)Tc complexes prepared in carrier-added conditions. The two radiolabeled complexes were stable with regard to trans chelation with cysteine, glutathione, and ethylenediaminotetraacetic acid and in rat and human sera. This study highlights the substitution-inert metal-fragment behavior of the [M(PS)2](+) framework, which reacts with suitable bidentate coligands to form stable hexacoordinated asymmetrical complexes. This feature makes it a promising platform on which to develop a new class of Re/Tc complexes that are potentially useful in radiopharmaceutical applications.

The aminophosphine ligand (2-aminoethyl)diphenylphosphine (edpp) has been coordinated to the W3(μ-S)(μ-S)3 cluster unit to afford trimetallic complex [W3S4Br3(edpp)3](+) (1(+)) in a one-step synthesis process with high yields. Related [W3S4X3(edpp)3](+) clusters (X = F(-), Cl(-), NCS(-); 2(+)-4(+)) have been isolated by treating 1(+) with the corresponding halide or pseudohalide salt. The structure of complexes 1(+) to 4(+) contains an incomplete W3S4 cubane-type cluster unit, and only one of the possible isomers is formed: the one with the phosphorus atoms trans to the capping sulfur and the amino groups trans to the bridging sulphurs. The remaining coordination position on each metal is occupied by X. Detailed studies using stopped-flow, (31)P{(1)H} NMR, and ESI-MS have been carried out in order to understand the solution behavior and the kinetics of interconversion among species 1(+), 2(+), 3(+), and 4(+) in solution. Density functional theory (DFT) calculations have been also carried out on the reactions of cluster 1(+) with the different anions. The whole set of experimental and theoretical data indicate that the actual mechanism of substitutions in these clusters is strongly dependent on the nature of the leaving and entering anions. The interaction between an entering F(-) and the amino group coordinated to the adjacent metal have also been found to be especially relevant to the kinetics of these reactions.

Three isomers of a new heteroditopic ligand that contains a di(1H-pyrazolyl)methyl (-CHpz2) moiety connected to a di(p-tolyl)phosphine group via a para-, meta-, or ortho-phenylene spacer (pL, mL, and oL, respectively) have been synthesized by using a palladium(0)-catalyzed coupling reaction between HP(p-tolyl)2 and the appropriate isomer of (IC6H4)CHpz2. The 1:1 complexes of silver(I) trifluoromethanesulfonate, Ag(OTf), were prepared to examine the nature of ligand coordination and the type of supramolecular isomer (monomeric, cyclic oligomeric, or polymeric) that would be obtained. The single crystal X-ray diffraction studies showed that [Ag(pL)](OTf), 1, and [Ag(mL)](OTf), 2, possessed cyclic dimeric dications, whereas [Ag(oL)](OTf), 3, was a coordination polymer. The polymeric chain in 3 could be disrupted by reaction with triphenylphosphine, and the resulting complex, [Ag(oL)(PPh3)](OTf), 4, possessed a monometallic cation where the ligand was bound to silver in a chelating κ(2)P,N- coordination mode. The solution structures of 1-4 were probed via a combination of IR, variable-temperature multinuclear ((1)H, (13)C, (31)P) NMR spectroscopy, as well as by electron spray ionization (ESI)(+) mass spectrometry. A related complex [Ag(m-IC6H4CHpz2)2](OTf), 5, was also prepared, and its solid-state and solution spectroscopic properties were studied for comparison purposes. These studies suggest that the cyclic structures of 1 and 2 are likely preserved but are dynamic in solution at room temperature. Moreover, both 3 and 4 have dynamic solution structures where 3 is likely extensively dissociated in CH3CN or acetone rather than being polymeric as in the solid state.

The synthesis and the photophysics of three dinuclear copper(I) complexes containing bis(bidentate)phosphine ligands are described. The steric constraint imposed by tetrakis(di(2-methoxyphenyl)phosphanyl)cyclobutane) (o-MeO-dppcb) in combination with 2,9-dimethyl-1,10-phenanthroline in one of the complexes leads to interesting photophysical properties. The compound shows an intense emission at room temperature in deoxygenated acetonitrile solution (Φ = 49%) and a long excited-state lifetime (13.8 μs). Interestingly, at low temperature, 77 K, the emission maximum shifts to lower energy, and the excited-state lifetime increases. This observation leads to the conclusion that a mixing between the excited triplet and singlet states is possible and that the degree of mixing and population of state strongly depends on temperature, as the energy difference is quite small. The electroluminescent properties of this compound were therefore tested in light-emitting electrochemical cells (LEECs), proving that the bright emission can also be obtained by electrically driven population of the singlet state.

The octahedral transition-metal complex [(dppa)Fe(Ph2P-N-PPh2)2] (1) [dppa = bis(diphenylphosphino)amine] with homofunctional bidentate ligands is described. The ligand exhibits hemilability due to its small bite angle and the steric repulsion of the coordinated donor groups. As the {Ph2P-N-PPh2}(-) ligand can act as an internal base, heterolytic cleavage of dihydrogen by complex 1 leads to the formation of the hydride complex [(dppa)(Ph2P-N-PPh2)Fe(H)(κ(1)-Ph2P-NH-PPh2)2] (2), representing an example of cooperative bond activation with a homofunctional hemilabile ligand. This study demonstrates that hemilability of homofunctionalized ligands can be affected by careful adjustment of geometric parameters.

We have developed a protocol for the direct coupling between methyl ester protected amino acids and the chlorido-gold(I)-phosphane (p-HOOC(C6H4)PPh2)AuCl. By applying the EDC·HCl/NHS strategy (EDC·HCl = N-ethyl-N'-(3-(dimethylamino)propyl)carbodiimide hydrochloride, NHS = N-hydroxysuccinimide), the methyl esters of l-phenylalanine, glycine, l-leucine, l-alanine, and l-methionine are coupled with the carboxylic acid of the gold complex in moderate to good yields (62-88%). All amino acid tagged gold complexes were characterized by (1)H and (13)C NMR spectroscopy and high-resolution mass spectrometry. As corroborated by measurement of the angle of optical rotation, no racemization occurred during the reaction. The molecular structure of the leucine derivative was determined by single-crystal X-ray diffraction. In the course of developing an efficient coupling protocol, the acyl chlorides (p-Cl(O)C(C6H4)PPh2)AuX (X = Cl, Br) were also prepared and characterized.

Two pentacoordinate mononuclear iron carbonyls of the form (bdt)Fe(CO)P2 [bdt = benzene-1,2-dithiolate; P2 = 1,1'-diphenylphosphinoferrocene (1) or methyl-2-{bis(diphenylphosphinomethyl)amino}acetate (2)] were prepared as functional, biomimetic models for the distal iron (Fe(d)) of the active site of [FeFe]-hydrogenase. X-ray crystal structures of the complexes reveal that, despite similar ν(CO) stretching band frequencies, the two complexes have different coordination geometries. In X-ray crystal structures, the iron center of 1 is in a distorted trigonal bipyramidal arrangement, and that of 2 is in a distorted square pyramidal geometry. Electrochemical investigation shows that both complexes catalyze electrochemical proton reduction from acetic acid at mild overpotential, 0.17 and 0.38 V for 1 and 2, respectively. Although coordinatively unsaturated, the complexes display only weak, reversible binding affinity toward CO (1 bar). However, ligand centered protonation by the strong acid, HBF4·OEt2, triggers quantitative CO uptake by 1 to form a dicarbonyl analogue [1(H)-CO](+) that can be reversibly converted back to 1 by deprotonation using NEt3. Both crystallographically determined distances within the bdt ligand and density functional theory calculations suggest that the iron centers in both 1 and 2 are partially reduced at the expense of partial oxidation of the bdt ligand. Ligand protonation interrupts this extensive electronic delocalization between the Fe and bdt making 1(H)(+) susceptible to external CO binding.

A series of phosphine-substituted ruthenium polypyridine complexes, cis(P,Cl)-[Ru(trpy)(Pqn)Cl]PF6 (cis-Cl), trans(P,MeCN)-[Ru(trpy)(Pqn)(MeCN)](PF6)2 (trans-PN), cis(P,MeCN)-[Ru(trpy)(Pqn)(MeCN)](PF6)2 (cis-PN), and [Ru(trpy)(dppbz)(MeCN)](PF6)2 (PP), were synthesized and crystallographically characterized (trpy = 2,2':6',2″-terpyridine, Pqn = 8-(diphenylphosphanyl)quinoline, and dppbz = 1,2-bis(diphenylphosphanyl)benzene). In electrochemical measurements for cis-PN and PP, the reduction of cis-PN resulted in the formation of trans-PN via cis-trans isomerization and that of PP proceeded via a two-electron-transfer reaction. The mechanism of the electrochemical behaviors is discussed through consideration of five-coordinated species, [Ru(trpy)(Pqn)](n+) or [Ru(trpy)(dppbz)](n+) (n = 0-2), formed by liberation of a monodentate labile ligand.

The reactions of potassium salts of the dithiocarbamates L {where L = pyrazolyldithiocarbamate (L1), 3,5-dimethylpyrazolyldithiocarbamate (L2), or indazolyldithiocarbamate (L3)} with the gold precursors [AuCl(PPh3)], [Au2Cl2(dppe)], [Au2Cl2(dppp)], or [Au2Cl2(dpph)] lead to the new gold(I) complexes [AuL(PPh3)] (1-3), [Au2L2(dppe)] (4-6), [(Au2L2)(dppp)] (7-9), and [Au2(L)2(dpph)] (10-12) {where dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, and dpph = 1,6-bis(diphenylphosphino)hexane}. These gold compounds were characterized by a combination of NMR and infrared spectroscopy, microanalysis, and mass spectrometry; and in selected cases by single-crystal X-ray crystallography. Compounds 4-6, which have dppe ligands, are unstable in solution for prolonged periods, with 4 readily transforming to the Au18 cluster [Au18S8(dppe)6]Cl2 (4a) in dichloromethane. Compounds 1-3 and 7-12 are all active against human cervical epithelioid carcinoma (HeLa) cells, but the most active compounds are 10 and 11, with IC50 values of 0.51 μM and 0.14 μM, respectively. Compounds 10 and 11 are more selective toward HeLa cells than they are toward normal cells, with selectivities of 25.0 and 70.5, respectively. Further tests, utilizing the 60-cell-line Developmental Therapeutics Program at the National Cancer Institute (U.S.A.), showed 10 and 11 to be active against nine other types of cancers.

A diiron dithiolate complex with a pendant phosphine coordinated to one of the iron centers, [(μ-SCH2)2N(CH2C6H4-o-PPh2){Fe2(CO)5}] (1), was prepared and structurally characterized. The pendant phosphine is dissociated together with a CO ligand in the presence of excess PMe3, to afford [(μ-SCH2)2N(CH2C6H4-o-PPh2){Fe(CO)2(PMe3)}2] (2). Redox reactions of 2 and related complexes were studied in detail by in situ IR spectroscopy. A series of new Fe(II)Fe(I) ([3](+) and [6](+)), Fe(II)Fe(II) ([4](2+)), and Fe(I)Fe(I) (5) complexes relevant to Hox, Hox(CO), and Hred states of the [FeFe]-hydrogenase active site were detected. Among these complexes, the molecular structures of the diferrous complex [4](2+) with the internal amine and the pendant phosphine co-coordinated to the same iron center and the triphosphine diiron complex 5 were determined by X-ray crystallography. To make a comparison, the redox reactions of an analogous complex, [(μ-SCH2)2N(CH2C6H5){Fe(CO)2(PMe3)}2] (7), were also investigated by in situ IR spectroscopy in the absence or presence of extrinsic PPh3, which has no influence on the oxidation reaction of 7. The pendant phosphine in the second coordination sphere makes the redox reaction of 2 different from that of its analogue 7.

To provide the mechanistic information of nitrogenase at a molecular level, much effort has been made to develop synthetic metal complexes that have enzyme-like reactivity. Herein we obtain an iron(II) complex binding with a tris(thiolato)phosphine ligand, [P(Ph)4][Fe(PS3″)(CH3CN)] [1; PS3″ = P(C6H3-3-Me3Si-2-S)3(3-)] that catalyzes the reduction of hydrazine, an intermediate and a substrate of nitrogenase. The substrate- and product-bound adducts, [N(Bu)4][Fe(PS3″)(N2H4)] (2) and [N(Et)4][Fe(PS3″)(NH3)] (3), respectively, are also synthesized. This work provides the feasibility that the late stage of biological nitrogen fixation can be conducted at a single iron site with a sulfur-rich ligation environment.

The hyperpolarization (HP) method signal amplification by reversible exchange (SABRE) uses para-hydrogen to sensitize substrate detection by NMR. The catalyst systems [Ir(H)2(IMes)(MeCN)2(R)]BF4 and [Ir(H)2(IMes)(py)2(R)]BF4 [py = pyridine; R = PCy3 or PPh3; IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene], which contain both an electron-donating N-heterocyclic carbene and a phosphine, are used here to catalyze SABRE. They react with acetonitrile and pyridine to produce [Ir(H)2(NCMe)(py)(IMes)(PPh3)]BF4 and [Ir(H)2(NCMe)(py)(IMes)(PCy3)]BF4, complexes that undergo ligand exchange on a time scale commensurate with observation of the SABRE effect, which is illustrated here by the observation of both pyridine and acetonitrile HP. In this study, the required symmetry breaking that underpins SABRE is provided for by the use of chemical inequivalence rather than the previously reported magnetic inequivalence. As a consequence, we show that the ligand sphere of the polarization transfer catalyst itself becomes hyperpolarized and hence that the high-sensitivity detection of a number of reaction intermediates is possible. These species include [Ir(H)2(NCMe)(py)(IMes)(PPh3)]BF4, [Ir(H)2(MeOH)(py)(IMes)(PPh3)]BF4, and [Ir(H)2(NCMe)(py)2(PPh3)]BF4. Studies are also described that employ the deuterium-labeled substrates CD3CN and C5D5N, and the labeled ligands P(C6D5)3 and IMes-d22, to demonstrate that dramatically improved levels of HP can be achieved as a consequence of reducing proton dilution and hence polarization wastage. By a combination of these studies with experiments in which the magnetic field experienced by the sample at the point of polarization transfer is varied, confirmation of the resonance assignments is achieved. Furthermore, when [Ir(H)2(pyridine-h5)(pyridine-d5)(IMes)(PPh3)]BF4 is examined, its hydride ligand signals are shown to become visible through para-hydrogen-induced polarization rather than SABRE.

A series of potent C,N-cycloplatinated(II) phosphine antitumor complexes containing fluorous substituents in the cyclometalated or the ancillary phosphine ligands [Pt(C-N)(PR3)Cl] or both have been synthesized and characterized. The crystal structure of [Pt(dmba){P(C6H4CF3-p)3}Cl]·2CH2Cl2 (dmba = dimethylaminomethyl)phenyl) has been established by X-ray diffraction. Values of IC50 of the new platinum complexes were calculated toward a panel of human tumor cell lines representative of ovarian (A2780 and A2780cisR) and breast cancers (T47D). Complexes containing P(C6H4CF3-p)3 as ancillary ligand (with a bulky and electronegative CF3 substituent in para position) were the most cytotoxic compounds in all the tested cancer cell lines. In some cases, the IC50 values were 16-fold smaller than that of cisplatin and 11-fold smaller than the non-fluorous analogue [Pt(dmba)(PPh3)Cl]. On the other hand, very low resistance factors (RF) in A2780cisR (cisplatin-resistant ovarian carcinoma) at 48 h were observed (RF ≈ 1) for most of the new compounds. Analysis of cell cycle was done for the three more active compounds in A2780. They arrest cell growth in G0/G1 phase in contrast to cisplatin (S phase) with a high incidence of late-stage apoptosis. They are also good cathepsin B inhibitors (an enzyme implicated in a number of cancer related events).

The synthesis and characterization of neutral mixed ligand complexes fac-[M(CO)3(P)(OO)] and cis-trans-[M(CO)2(P)2(OO)] (M = Re, (99m)Tc), with deprotonated acetylacetone or curcumin as the OO donor bidentate ligands and a phosphine (triphenylphosphine or methyldiphenylphosphine) as the monodentate P ligand, is described. The complexes were synthesized through the corresponding fac-[M(CO)3(H2O)(OO)] (M = Re, (99m)Tc) intermediate aqua complex. In the presence of phosphine, replacement of the H2O molecule of the intermediate complex at room temperature generates the neutral tricarbonyl monophosphine fac-[Re(CO)3(P)(OO)] complex, while under reflux conditions further replacement of the trans to the phosphine carbonyl generates the new stable dicarbonyl bisphosphine complex cis-trans-[Re(CO)2(P)2(OO)]. The Re complexes were fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography showing a distorted octahedral geometry around Re. Both the monophosphine and the bisphosphine complexes of curcumin show selective binding to β-amyloid plaques of Alzheimer's disease. At the (99m)Tc tracer level, the same type of complexes, fac-[(99m)Tc(CO)3(P)(OO)] and cis-trans-[(99m)Tc(CO)2(P)2(OO)], are formed introducing new donor combinations for (99m)Tc(I). Overall, β-diketonate and phosphine constitute a versatile ligand combination for Re(I) and (99m)Tc(I), and the successful employment of the multipotent curcumin as β-diketone provides a solid example of the pharmacological potential of this system.

The syntheses and the characterization by chemical analysis, (1)H and (31)P NMR spectroscopy, and mass spectrometry of a series of linear triphenylphosphine gold(I) complexes with substituted N-heterocycle ligands (L), [(PPh3)Au(I)(L)](+), is reported. The reaction of [(PPh3)Au(L)](+) (L = Cl(-) or substituted N- heterocyclic pyridine) with the C-terminal (Cys3His) finger of HIVNCp7 shows evidence by mass spectrometry (ESI-MS) and (31)P NMR spectroscopy of a long-lived {(PPh3)Au}-S-peptide species resulting from displacement of the chloride or pyridine ligand by zinc-bound cysteine with concomitant displacement of Zn(2+). In contrast, reactions with the Cys2His2 finger-3 of the Sp1 transcription factor shows significantly reduced intensities of {(PPh3)Au} adducts. The results suggest the possibility of systematic (electronic, steric) variations of "carrier" group PR3 and "leaving" group L as well as the nature of the zinc finger in modulation of biological activity. The cytotoxicity, cell cycle signaling effects, and cellular accumulation of the series are also reported. All compounds display cytotoxicity in the micromolar range upon 96 h continuous exposure to human tumor cells. The results may have relevance for the reported inhibition of viral load in simian virus by the gold(I) drug auranofin.

A one-pot, multicomponent, coordination-driven self-assembly approach was used to synthesize the first examples of neutral bridging phosphine oxide donor-based supramolecular coordination complexes. The complexes were self-assembled from a fac-Re(CO)3 acceptor, an anionic bridging O donor, and a neutral soft phosphine or hard phosphine oxide donor.

The photophysical properties of bis(phosphine) Pt(II) complexes constructed from 2,6-bis(pyrid-3-ylethynyl) aniline and 2,6-bis(pyrid-4-ylethynyl) aniline vary significantly, even though the complexes differ only in the position of the coordinating nitrogen. By capping the ligands with an aryl bis(phosphine) Pt(II) metal acceptor, the photophysical properties of the two isomeric systems were directly compared, revealing that the low-energy absorption and emission bands of the two systems were separated by 30 nm (1804 cm(-1)) and 39 nm (1692 cm(-1)), respectively. From the analysis of time-dependent density functional (TD-DFT) calculations and excited-state lifetime measurements, it was determined that the nature of the Pt-N bond in the HOMO and the sums of the radiative (k(rad)) and nonradiative (k(nr)) rate constants were significantly different in the two systems. As the dominant nonradiative decay pathway in aniline systems is relaxation from the triplet state through intersystem crossing (ISC), the difference in k(nr) can be ascribed to changes in ISC between isomers of the bis(phosphine) Pt(II)-capped 2,6-bis(pyrid-3-ylethynyl) aniline system. It was also determined that the photophysical properties of these capped systems can be altered by functionalizing the aryl capping ligand on the bis(phosphine) Pt(II) metal center, which perturbs the molecular orbitals involved in the observed optical transitions. In addition, an isoelectronic bis(phosphine) Pd(II)-capped system was prepared for comparison with the bis(phosphine) Pt(II) suite of complexes. The Pd(II) system showed significant changes in its low-energy absorption band, but preserved the characteristic emissive properties of its Pt(II) analogue with an even higher quantum yield.

Protonation-assisted deoxygenation of a mono-oxo molybdenum center has been observed in many oxotransferases when the enzyme removes an oxo group to regenerate a substrate binding site. Such a reaction is reported here with discrete synthetic mono-oxo bis(dithiolene) molybdenum and tungsten complexes, the chemistry of which had been rarely studied because of the instability of the resulting deoxygenated products. An addition of tosylic acid to an acetonitrile solution of [Mo(IV)O(S2C2Ph2)2](2-) (1) and [W(IV)O(S2C2Ph2)2](2-) (2) results in the loss of oxide with a concomitant formation of novel deoxygenated complexes, [M(MeCN)2(S2C2Ph2)2] (M = Mo (3), W (4)), that have been isolated and characterized. Whereas protonation of 1 exclusively produces 3, two different reaction products can be generated from 2; an oxidized product, [WO(S2C2Ph2)2](-), is produced with 1 equiv of acid while a deoxygenated product, [W(MeCN)2(S2C2Ph2)2] (4), is generated with an excess amount of proton. Alternatively, complexes 3 and 4 can be obtained from photolysis of [Mo(CO)2(S2C2Ph2)2] (5) and [W(CO)2(S2C2Ph2)2] (6) in acetonitrile. A di- and a monosubstituted adducts of 3, [Mo(CO)2(S2C2Ph2)2] (5) and [Mo(PPh3)(MeCN)(S2C2Ph2)2] (7) are also reported.

Three new lanthanide heterocyclic β-diketonate complexes [Dy(PPI)3(EtOH)2] (1), [Dy(PPI)3(DPEPO)] (2), and [Tb(PPI)3(DPEPO)] (3) [where HPPI = 3-phenyl-4-propanoyl-5-isoxazolone and DPEPO = bis(2-(diphenylphosphino)phenyl)ether oxide] have been synthesized and fully characterized. Single-crystal X-ray diffraction analyses reveal that these complexes are mononuclear and that the central Ln(III) ion is coordinated to eight oxygen atoms that are provided by three bidentate β-diketonate ligands and ethanol or bidentate DPEPO in a distorted square antiprismatic geometry. These complexes have high molar absorption coefficients (up to 3 × 10(4) M(-1) cm(-1) at 285 nm) and display strong visible and, for Dy(III), NIR luminescence upon irradiation at the ligand-centered band in the range 250-350 nm. The emission quantum yields and the luminescence lifetimes at room temperature are 3 ± 0.5% and 15 ± 1 μs for 1, 12 ± 2% and 33 ± 1 μs for 2, and 42 ± 6% and 795 ± 1 μs for 3. Moreover, the crystals of 2 and 3 exhibit brilliant triboluminescence, visible in daylight.

A systematic library of 24 nickel(II) complexes with bidentate diphosphane ligands was synthesized, and the solid-state structures of five of them were determined with X-ray crystallography. The compounds C1-C3 are common P2Ni(II)X2-type complexes, while C4 contains a unique [P2Ni(II)(NH3)(OAc)](+) square-planar structure with a P2NO donor set and C5 constitutes a rare [(P2Ni(II))2(μ-OH)2](2+) dinuclear compound. The catalytic activity of all complexes was tested in the hydrogenation and/or isomerization of 1-octene in a CH2Cl2/CH3OH reaction medium. Catalyst precursors bearing ligands with o-alkoxy aryl rings selectively hydrogentate 1-octene to n-octane, while catalytic systems comprising ligands without the o-alkoxy functionality selectively isomerize the substrate to a mixture of internal alkenes, mostly cis- and trans-2-octene. The conversion is enhanced by equipping the ligand aryl rings with electron-donating alkoxy groups, by increasing the steric bulk of the backbone and/or the aryl rings, by employing relatively noncoordinating anions, and by adding a base as the cocatalyst. Using the compound [Ni(L3X)I2] as the catalyst precursor and upon application of standard hydrogenation conditions, full conversion of the substrate was achieved in 1 h to isomerization products only (TON = 1940). When a catalytic amount of the base is added, a similar result is obtained even in the absence of H2. A maximum TON of 4500 in 1 h with 96% selectivity for n-octane was achieved by employing [Ni(oMeO-L3X)(NH3)(OAc)]PF6 as the catalyst precursor.

The synthesis and characterization of a new series of neutral, six-coordinated mixed-ligand compounds [M(III)(PS)2(L)] (M = Re; (99)Tc), where PS is bis(arylalkyl)- or trialkylphosphinothiolate and L is dithiocarbamate, are reported. Stable [M(III)(PS)2(L)] complexes were easily synthesized, in good yield, starting from precursors where the metal was in different oxidation states (III, V, and VII), involving ligand-exchange and/or redox-substitution reactions. The compounds were characterized by elemental analysis, positive-ion electrospray ionization mass spectrometry, multinuclear NMR spectroscopy, cyclic voltammetry, and X-ray diffraction analysis. All complexes are constituted by the presence of the [M(III)(PS)2](+) moiety, where two phosphinothiolate ligands are tightly bound to the metal and the remaining two positions are saturated by a dithiocarbamate chelate, also carrying bulky bioactive molecules [e.g., (2-methoxyphenyl)piperazine]. X-ray analyses were performed on crystalline specimens of four different Re/(99)Tc compounds sharing a distorted trigonal-prismatic geometry, with a P2S4 coordination donor set. The possibility of easily preparing these [M(III)(PS)2(L)] complexes, starting from the corresponding permetalate anions, in mild reaction conditions and in high yield, lays the first stone to the preparation of a new series of M(III)-based (M = (99m)Tc/(188)Re) compounds potentially useful in theragnostic applications.

Molybdenum dinitrogen complexes are presented which are supported by novel hybrid tripod ligands of the type Me-C(CH2PPh2)2(CH2P(i)Pr2) (trpd-1) and H-C(CH2PPh2)(CH2P(i)Pr2)2 (trpd-2) having mixed dialkylphosphine/diarylphosphine donor groups. Reaction of the ligand trpd-1 with [MoI3(thf)3] followed by sodium amalgam reduction in the presence of the dppm gives the dinitrogen complex [Mo(N2)(trpd-1)(dmpm)] where trpd-1 is coordinated in a κ(3) fashion. The complex exhibits a moderate activation of N2 which enables its protonation under retention of the pentaphosphine ligation. Replacement of dmpm by the sterically more demanding coligand dppm is found to hamper coordination of N2 and leads to [Mo(trpd-1)(dppm)], the first structurally characterized five-coordinate Mo(0) complex with a phosphine-only ligand sphere. Employing the ligand trpd-2 along with the diphosphines dmpm and dppm in an analogous synthetic route results in a mixture of the bis(dinitrogen) complexes trans-[Mo(N2)2(κ(2)-trpd-2)(diphosphine)] and trans-[Mo(N2)2(iso-κ(2)-trpd-2)(diphosphine)] where the tripod ligand trpd-2 coordinates with two phosphine arms and one phosphine group (PPh2 or P(i)Pr2, respectively) is free. Similar results are obtained with the pure alkyl- and arylphosphine tripod ligands H-C(CH2P(i)Pr2)3 (trpd-3) and H-C(CH2PPh2)3 (tdppmm), leading to trans-[Mo(N2)2(κ(2)-trpd-3)(diphos)] and trans-[Mo(N2)2(κ(2)-tdppmm)(dmpm)], respectively. The electronic and steric reasons for the experimental findings are considered, and the implications of the results for the area of synthetic nitrogen fixation with molybdenum phosphine systems are discussed.

This work details the synthesis and structural identification of a series of complexes of the (η(5)-C5Me5)Ir(III) unit coordinated to cyclometalated bis(aryl)phosphine ligands, PR'(Ar)2, for R' = Me and Ar = 2,4,6-Me3C6H2, 1b; 2,6-Me2-4-OMe-C6H2, 1c; 2,6-Me2-4-F-C6H2, 1d; R' = Et, Ar = 2,6-Me2C6H3, 1e. Both chloride- and hydride-containing compounds, 2b-2e and 3b-3e, respectively, are described. Reactions of chlorides 2 with NaBArF (BArF = B(3,5-C6H3(CF3)2)4) in the presence of CO form cationic carbonyl complexes, 4(+), with ν(CO) values in the narrow interval 2030-2040 cm(-1), indicating similar π-basicity of the Ir(III) center of these complexes. In the absence of CO, NaBArF forces κ(4)-P,C,C',C″ coordination of the metalated arm (studied for the selected complexes 5b, 5d, and 5e), a binding mode so far encountered only when the phosphine contains two benzylic groups. A base-catalyzed intramolecular, dehydrogenative, C-C coupling reaction converts the κ(4) species 5d and 5e into the corresponding hydrido phosphepine complexes 6d and 6e. Using CD3OD as the source of deuterium, the chlorides 2 undergo deuteration of their 11 benzylic positions whereas hydrides 3 experience only D incorporation into the Ir-H and Ir-CH2 sites. Mechanistic schemes that explain this diversity have come to light thanks to experimental and theoretical DFT studies that are also reported.

The tris(phosphinoamide)-bridged Fe(II)Fe(II) diiron complex Fe(μ-(i)PrNPPh2)3Fe(η(2)-(i)PrNPPh2) (1) can be reduced in the absence or presence of PMe3 to generate the mixed-valence Fe(II)Fe(I) complexes Fe(μ-(i)PrNPPh2)3Fe(PPh2NH(i)Pr) (2) or Fe(μ-(i)PrNPPh2)3Fe(PMe3) (3), respectively. Following a typical oxidative group transfer procedure, treatment of 2 or 3 with organic azides generates the mixed-valent Fe(II)Fe(III) imido complexes Fe((i)PrNPPh2)3Fe≡NR (R = (t)Bu (4), Ad (5), 2,4,6-trimethylphenyl (6)). These complexes represent the first examples of first-row bimetallic complexes featuring both metal-ligand multiple bonds and metal-metal bonds. The reduced complexes 2 and 3 and imido complexes 4-6 have been characterized via X-ray crystallography, Mössbauer spectroscopy, cyclic voltammetry, and SQUID magnetometry, and a theoretical description of the bonding within these diiron complexes has been obtained using computational methods. The effect of the metal-metal interaction on the electronic structure and bonding in diiron imido complexes 4-6 is discussed in the context of similar monometallic iron imido complexes.

A series of highly phosphorescent PtAg2 heterotrinuclear alkynyl complexes with bis(diphenylphosphinomethyl)phenylphosphine (dpmp) were prepared and characterized structurally. The solution phosphorescence with various emitting colors is systematically modulated by modifying substituents as well as π-conjugated systems in aromatic acetylides. The crystals, powders, or films exhibit reversible stimuli-responsive phosphorescence changes upon exposure to vapor of MeCN, pyridine, DMF, etc., resulting from perturbation of d(8)-d(10) metallophilic interaction in the excited states as a consequence of the formation/disruption of Ag-solvent bonds. Both experimental and time-dependent density functional theory (TD-DFT) studies demonstrate that d(8)-d(10) metallophilic interaction exerts a crucial role on phosphorescent characteristics due to the PtAg2 cluster-based (3)[d → p] state. This study affords a paradigm for phosphorescence modulation in d(8)-d(10) heteronuclear complexes.

Analysis of the structures of three (PNP)Pd-Pd(PNP) dimers [where PNP stands for anionic diarylamido/bis(phosphine) pincer ligands] has been carried out with the help of single-crystal X-ray diffractometry and density functional theory (DFT) calculations on isolated molecules. The three dimers under study possess analogous ancillary ligands; two of them differ only by an F versus Me substituent in a remote (five bonds away from Pd) position of the pincer ligand. Despite these close similarities, X-ray structural determinations revealed two distinct structural motifs: a highly symmetric molecule with a long Pd-Pd bond or a highly distorted molecule with Pd-Pd bonds ca. 0.14 Å shorter. DFT calculations on a series of (PNP)Pd-Pd(PNP) dimers (as molecules in the gas phase) confirmed the existence of these distinct minima for dimers carrying large isopropyl substituents on the P-donor atoms (as in the experimental structure). These minima are nearly isoergic conformers. Evidently, the electronically preferred symmetric structure for the dimer (with a square-planar environment about Pd and a linear N-Pd-Pd-N vector) is not sterically possible with the preferred Pd-Pd distance. Thus, the minima correspond to either a symmetric structure with a long Pd-Pd bond distance or a structure with a short Pd-Pd distance but with substantial distortions in the Pd coordination environment to alleviate steric conflict. This notion is supported by finding only a single minimum (symmetric and with short Pd-Pd bonds) for each of the dimers carrying smaller substituents (H or Me) on the P atoms, regardless of the remote substitution.