The syntheses and characterization of new dirhodium complexes based on the electron acceptor ligand dipyrido[3,2-a:2´,3´-c]phenazine (dppz) and its derivatives are reported. These complexes have been shown to photocleave pUC18 plasmid in vitro under irradiation with visible light which results in the nicked, circular form of DNA. Unlike typical DNA photocleavage agents, the new compounds are capable of photocleaving DNA in the absence of oxygen as well as in the presence of oxygen. The toxicity of the complexes which contain the electron acceptor dppz ligand toward human skin cells increases when the cell cultures are irradiated with visible light. In contrast, the photocytotoxicity of those complexes that do not contain the dppz do not differ from cytotoxicity in the dark. The chemistry of the newly synthesized dirhodium-dppz complexes with glutathione, which is considered to be an important molecule in the deactivation of metal-based drugs, has also been investigated. The results show that glutathione reversibly reduces [Rh2(µ-O2CCH3)2(dppz)2]2+ (6) and [Rh2(µ-O2CCH3)2(dppz)(bpy)]2+ (7), and that they are easily reoxidized to the original form in air. EPR measurements and DFT calculations indicate that the additional electron is delocalized in the ligand orbitals. The molecular characteristics that affect the in vitro activity of dirhodium complexes is discussed. The lability of the groups coordinated to the dirhodium complexes is a significant factor that influences the toxicity of the complexes. In addition, the presence of labile solvent molecules and monodentate acetate groups provide potential “open sites” accessible for nucleophilic substitution, as opposed to these sites being occupied by non-labile groups that reduce the reactivity of the complexes. Finally, the results also demonstrate that the carbonato-bridged complexes of the type [Rh2(µ-O2CO)2(diimine)2(H2O)2]2+ are useful precursors to access new dirhodium-diimine compounds that are not accessible from the acetate precursors. These compounds react with trifluoroacetamide, 2-pyrrolidinone, and trifluoroacetic acid to form products in which the carbonato ligands are substituted in favor of the new bridging group. This work provides a foundation for the preparation of new series of dirhodium complexes that contain the dppz ligand and bridging ligands other than acetate.

The syntheses and characterization of new dirhodium complexes based on the electron acceptor ligand dipyrido[3,2-a:2´,3´-c]phenazine (dppz) and its derivatives are reported. These complexes have been shown to photocleave pUC18 plasmid in vitro under irradiation with visible light which results in the nicked, circular form of DNA. Unlike typical DNA photocleavage agents, the new compounds are capable of photocleaving DNA in the absence of oxygen as well as in the presence of oxygen. The toxicity of the complexes which contain the electron acceptor dppz ligand toward human skin cells increases when the cell cultures are irradiated with visible light. In contrast, the photocytotoxicity of those complexes that do not contain the dppz do not differ from cytotoxicity in the dark. The chemistry of the newly synthesized dirhodium-dppz complexes with glutathione, which is considered to be an important molecule in the deactivation of metal-based drugs, has also been investigated. The results show that glutathione reversibly reduces [Rh2(µ-O2CCH3)2(dppz)2]2+ (6) and [Rh2(µ-O2CCH3)2(dppz)(bpy)]2+ (7), and that they are easily reoxidized to the original form in air. EPR measurements and DFT calculations indicate that the additional electron is delocalized in the ligand orbitals. The molecular characteristics that affect the in vitro activity of dirhodium complexes is discussed. The lability of the groups coordinated to the dirhodium complexes is a significant factor that influences the toxicity of the complexes. In addition, the presence of labile solvent molecules and monodentate acetate groups provide potential “open sites” accessible for nucleophilic substitution, as opposed to these sites being occupied by non-labile groups that reduce the reactivity of the complexes. Finally, the results also demonstrate that the carbonato-bridged complexes of the type [Rh2(µ-O2CO)2(diimine)2(H2O)2]2+ are useful precursors to access new dirhodium-diimine compounds that are not accessible from the acetate precursors. These compounds react with trifluoroacetamide, 2-pyrrolidinone, and trifluoroacetic acid to form products in which the carbonato ligands are substituted in favor of the new bridging group. This work provides a foundation for the preparation of new series of dirhodium complexes that contain the dppz ligand and bridging ligands other than acetate.

The anticancer properties of dirhodium tetraacetate were discovered in the 1970's, and subsequently motivated the research of several dirhodium paddlewheel derivatives. The promising results of this research led the Dunbar group to investigate the biological properties of dirhodium partial paddlewheel compounds. Previous work in our group has focused on dirhodium carboxylate derivatives with a series of diimine ligands, namely 1,10-phenanthroline (phen), dipyrido[3,2-f:2',3'-h]quinoxaline (dpq), dipyrido[3,2a:2',3'c] phenazine (dppz), and benzo[i]dipyrido[3,2-a:2',3'-c]phenazine) (dppn). Current research has expanded this diimine series by substituting the carobxylate bridging group with p-methoxyphenylphosphine (PMP). This new series of compounds was characterized by several techniques, including: X-Ray crystallography, 1H NMR spectroscopy, and electronic absorption spectroscopy. The cytotoxicity of these compounds towards HeLa cells was investigated in presence and absence of light in an effort to investigate the ability to use these compounds as photodynamic therapy (PDT) agents. Cytotoxicity measurements were carried out using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. It was found that in the dark [Rh2(PMP)2(dppz)2][BF4]2 (the dppz derivative of the dirhodium PMP compound) had no cytotoxicity towards HeLa cells, but experienced a 7 fold increase in cytotoxicity upon irradiation (with lambdai_rr equal to 350 nm). This dramatic increase in cytotoxicity upon irradiation makes this compound a potential PDT agent. Diiridium (II,II) compounds were prepared in a dual attempt to determine how the properties of the dirhodium core effect the biological activities of these compounds, as well as investigate the biological activity of a set of compounds that has yet to be explored. The compound [Ir2(DTolF)2(CH3CN)6][BF4]2 was chosen because it has a well understood dirhodium analogue, and it is a known compound. However, it was discovered that there was a potential silver contamination in the final product, stemming from the silver trifluoroacetate oxidant used during synthesis. Consequently, a new method of preparing this compound was required. The new synthetic pathway for the diiridium compound [Ir2(DTolF)2(CH3CN)6][BF4]2 was devised, and the cytotoxicity and photocytotoxicity studies were performed for the first time (to our knowledge) on a diiridium (II,II) compound. Despite the stability of the compound, it was determined to be highly toxic, both in the dark and upon irradiation.

No description available.

Three new tetrakis [Rh2(PhNCOCH3)4·xNCR] (R = {2-CH3}C6H4 (x=2), R = {3-CH3}C6H4 (x=1), R = (3-CN)C6H4∞ (x=1)) complexes have been synthesized and characterized. These complexes were characterized by IR and 1H NMR spectroscopies and X-ray crystallography which solved with R1<0.05. [Rh2(PhNCOCH3)4·2NC{2-CH3}C6H4] was triclinic (a=9.79Å, b=14.79Å, c=16.36Å, α=103.84⁰, β=99.17⁰, γ=99.77⁰, P-1(#2), μCN=2227.78cm-1, Rh-Rh=2.42Å, N-C=1.13Å, 1.14Å, Rh-N=2.34Å, 2.35Å, Rh-N-C=151.6⁰, 152.5⁰, Rh-Rh-N=173.0⁰, 174.6⁰). [Rh2(PhNCOCH3)4·NC{3-CH3}C6H4] was triclinic (a=11.71Å, b=13.02Å, c=13.40Å, α=72.34⁰, β=66.78⁰, γ=82.74⁰, P-1(#2), μCN=2241.28cm-1, Rh-Rh=2.40Å, N-C=1.14Å, Rh-N=2.16Å, Rh-N-C=166.3⁰, Rh-Rh-N=175.9⁰). [Rh2(PhNCOCH3)4·2NC{3-CN}C6H4]∞ was triclinic (a=11.88Å, b=13.30Å, c=14.88Å, α=77.98⁰, β=74.61⁰, γ=65.48⁰, P-1(#2), μCN=2233.57cm-1, Rh-Rh=2.41Å, N-C=1.13Å, 1.13Å, Rh-N=2.18Å, 2.38Å, Rh-N-C=166.8⁰, 127.7⁰, Rh-Rh-N=178.4⁰, 175.4⁰). The bond distances, bond angles and bonding interactions (σ and π) are similar to the metal-carbene bond formed during carbenoid transformations catalyzed by dirhodium(II) compounds.

The study of the mechanism of action of an antitumor active drug is essential for improving the efficacy and reducing the side effects of the drug as well as for developing better alternatives. In this vein, reactions of dirhodium compounds with DNA oligonucleotides were investigated by the techniques of mass spectrometry, HPLC, and NMR spectroscopic analytical methods. The relative reactivities of three dirhodium compounds, namely Rh2(O2CCH3)4, Rh2(O2CCF3)4, and [Rh2(O2CCH3)2(CH3CN)6](BF4)2, with DNA oligonucleotides were studied and compared to the clinically used anticancer drugs cisplatin and carboplatin using both MALDI and ESI mass spectrometric methods. The compound Rh2(O2CCF3)4 exhibits the highest reactivity among the dirhodium compounds, which is comparable to cisplatin, followed by [Rh2(O2CCH3)2(CH3CN)6](BF4)2, and finally Rh2(O2CCH3)4 which is the least reactive. Various dirhodium-oligonucleotide adducts were detected with both MALDI and ESI methods, which involve substitution of different numbers of the original ligands of the given dirhodium compound. ESI MS was found to be a sufficiently soft ionization method for detecting intact metal adducts, and CID MS-MS was useful for detecting weakly bound species such as axial adducts [M+Rh2(O2CCH3)4] and for comparing the relative bond strength between ligands in the metal adduct. A combination of anion exchange HPLC purification and enzymatic digestion studies of the adducts of Rh2(O2CCH3)4 with the 5'-CCTTCAACTCTC oligonucleotide revealed that Rh2(O2CCH3)4 binds to the center or to the ends of the oligonucleotide sequence by displacement of one or two acetate groups. Kinetic products of the type [M+Rh2(O2CCH3)3] obtained from the reaction of Rh2(O2CCH3)4 with 5'-CTCTCAACTTCC were separated by employing both reverse phase and anion exchange HPLC methods. The adduct that involves binding of the dirhodium unit to the exocyclic N4 atom of C5 and the N7 of A6 was found to be most stable whereas other adducts involving binding of C3 or C12 residues are clearly less stable. Reaction of cis-[Rh2(DAP)(O2CCH3)3(CH3OH)](O2CCH3) (DAP = 1,12- diazaperylene) with 5'-CTCTCAACTTCC produced a major adduct in which DAP group intercalates between 6A and 7A in the double stranded adduct with the rhodium atom that is not coordinated to the DAP group forming a covalent bond to the N7 atom of 6A which lends stability to the adduct.

No description available.

The complex molecule of the title compound, [Rh2{N(C6H5)COCH3}4(C8H7N)2], exhibits inversion symmetry. The four acetamidate ligands bridging the dirhodium core are arranged in a 2,2-trans manner with two N atoms and two O atoms coordinating to each RhIIatom trans to one another. The Neq - Rh - Rh - Oeq torsion angles on the acetamidate bridge vary between -4.07 (5) and -6.78 (7)°. The axial nitrile ligands complete the distorted octahedral coordination sphere of each RhIIatom and show a nonlinear coordination with Rh - N - C bond angles of 151.6 (3) and 152.5 (3)°. The bond lengths of the two nitrile triple bonds are 1.133 (5) and 1.137 (5) Å.

No description available.

Podocarpic acid (a diterpenoid resin acid extracted from the Podocarpacea specie of plants) has shown cytotoxicity against carcinoma of the nasopharynx. Since this discovery has been made, research has been performed in order to alter the structure of the resin acid so as to increase the anticancer activity. The carboxylic acid and phenol functional groups, which are present in podocarpic acid, make it possible to synthesize new derivatives selectively at the C-15, C-13, and C-7 positions as well as by substitution of the phenol hydroxyl group. Thus numerous derivatives can be prepared, in high yield, for the purpose of investigating their potential, as new drug leads for the treatment of cancer. In this study, Doyle's catalyst (Dirhodium tetrakis caprolactamate) was used to form a novel derivative in high yield (85%) which contained a 3-membered aziridine ring at the C-6 and C-7 position. The main thrust of this research involved the formation a series of novel derivatives of the aziridine compound by utilizing phenol and m-chlorophenol as nucleophiles to open the aziridine ring. These novel compounds will now be sent to the National Institute of Health (NIH) for bioassay against 60 human cancer cell lines.