Fundamentals of H2 Binding and Reactivity on Transition Metals Underlying Hydrogenase Function and H2 Production and Storage

The orientation distribution of a textured polycrystalline material has been traditionally determined from a few individual pole figures of lattice planes hkl, measured by x-ray or neutron diffraction A new method is demonstrated that uses the whole diffraction spectrum, rather than extracted peak intensities, by combining the orientation distribution calculation with the crystallographic Rietveld method The feasibility of the method is illustrated with time-of-flight neutron diffraction data of experimentally deformed polycrystalline calcite It is possible to obtain quantitative information on texture, crystal structure, microstructure, and residual stress from highly incomplete pole figures and from regions of the diffraction spectrum containing many overlapping peaks The approach provides a key for quantitative texture analysis of low symmetry compounds and of composites with complicated diffraction spectra

Combined texture and structure analysis of deformed limestone from time-of-flight neutron diffraction spectra

Reactions of transition metal dihydrogen complexes

This Account describes a new type of intermolecular interaction, the H‚‚‚H or dihydrogen bond, which operates between a conventional hydrogen bond donor such as an NH or OH bond as the weak acid component and an element-hydride bond as the weak base component, where the element in question can be a transition metal or boron. The interaction, which involves a close approach of protonic and hydridic hydrogens, has been characterized by crystallography, including neutron diffraction, and by physical and theoretical methods. These interactions occur in the so-called second or outer coordination sphere of a metal complex, as distinct from the first or inner sphere of the ligands directly bound to the metal. Taube1 has drawn attention to the importance of the outer solvent sphere in certain electron transfer processes, but otherwise very little is known about the structure and energetics of the outer sphere, and little attention2 has been given to the possibility of its control and organization. By selectively stabilizing the transition state, such interactions might be capable of accelerating specific reactions and so provide a general strategy with useful applications in catalysis. Conventional hydrogen bonds are formed between a proton donor, such as an OH or NH group, and a proton acceptor, such as an oxygen or nitrogen lone pair,3 but in all such cases a nonbonding electron pair acts as the weak base component. In rare cases, π-bonds4 and even metal atoms in metal complexes5 have also been shown to act as weak proton acceptors. A wide variety of element-hydrogen σ bonds, such as B-H and M-H (M ) transition metal), act as unexpectedly efficient hydrogen bond acceptors toward conventional proton donors, such as O-H and N-H groups. The resulting E-H‚‚‚H-X systems have close H‚‚‚H contacts (1.75-1.9 Å) and they have therefore been termed “H‚‚‚H or dihydrogen bonds”.6 Their heats of interaction are substantial (3-7 kcal mol-1) and lie in the range found for conventional H-bonds. Both interand intramolecular versions have been identified, and a number of reactions involving these new H-bonds have also been found. A significant feature of the work has been the close cooperation among synthetic, physical, crystallographic, and theoretical approaches.

A new intermolecular interaction: unconventional hydrogen bonds with element-hydride bonds as proton acceptor.

The demonstration in the 1960's that cis-diamminedichloroplatinum(II), or cisplatin, inhibits cellular division of Escherichia coli1 led to the subsequent discovery that this simple coordination compound is also an effective antitumor agent in mouse models.2 Subsequent studies validated cisplatin as an effective anticancer agent in humans as well,3–7 and FDA approval of cisplatin for the treatment of metastatic ovarian and testicular cancers was granted in 1978.8 Its introduction as a chemotherapeutic agent significantly improved the survival outlook for many cancer patients; the cure rate for testicular cancer before the approval of cisplatin was less than 10%, significantly lower than the 90% cure rate attained with modern platinum chemotherapy.9,10

Cisplatin kills cancer cells primarily by cross-linking DNA and inhibiting transcription.11 The chemical origin of this process begins when cisplatin enters the cell and undergoes aquation involving loss of one or both chloride ligands. The resulting platinum(II) aqua complexes are potent electrophiles that readily react with a number of biological ligands with loss of the bound water molecules. The purine bases of nucleic acids are strongly nucleophilic at the N7 position. Thus, cisplatin binds readily to DNA, forming primarily bifunctional adducts with loss of both chloride ligands. The major cisplatin-DNA adduct is the intrastrand 1,2-d(GpG) cross-link, which accounts for 60–65% of the bound platinum.12 The resulting Pt-DNA adducts, which distort and bend the DNA structure,13–15 impede transcription.16 The downstream effects of transcription inhibition ultimately lead to cell death.

Despite its great curative success in testicular cancer, cisplatin is not universally effective in other cancer types and induces a number of toxic side effects.17–19 Additionally, certain cancers are resistant to cisplatin therapy. This resistance is either intrinsic or developed during prolonged treatment.20,21 To circumvent these problems, new platinum complexes have been pursued and investigated for their antitumor properties. Although well over a thousand complexes have been prepared and tested thus far,22 only two other platinum drugs are approved for clinical use worldwide, and three additional compounds are approved for regional use in Asia.23 These complexes, displayed in Chart 1, operate with a mechanism of action similar to that of cisplatin, which involves DNA binding and transcription inhibition.






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Chart 1


Chemical structures of the clinically used platinum-based anticancer drugs. The top three complexes, cisplatin, carboplatin, and oxaliplatin, are approved for use worldwide. The bottom three complexes, nedaplatin, lobaplatin, and heptaplatin, are approved for use in Japan, China, and Korea, respectively.

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Synthetic Methods for the Preparation of Platinum Anticancer Complexes

The compound of formula FeH{sub 4}(PEtPh{sub 2}){sub 3} has been established by neutron diffraction to possess the structure and linkage cis,mer-Fe(H{sub 2})(PEtPh{sub 2}){sub 3}, and thus be generally similar in structure to cis,mer-Fe(H){sub 2}(N{sub 2})(PEtPh{sub 2}){sub 3}, whose structure has been determined by X-ray diffraction. The Fe-hydride distances in Fe(H){sub 2}(PEtPh{sub 2}){sub 3} are 1.538 (7) {angstrom} (trans to H{sub 2}) and 1.514 (6) {angstrom} (trans to PEtPh{sub 2}), and the Fe-H (of H{sub 2}) distances are 1.607 (8) and 1.576 (9) {angstrom}. The H-H distance in coordinated dihydrogen is 0.821 (10) {angstrom}, but the H-H bond adopts an orientation unique among structurally characterized octahedral H{sub 2} complexes: staggered with respect to the cis Fe-P and Fe-H axes. Vibrational frequencies of the Fe(H){sub 2}(H{sub 2}) substructure have been measured by difference inelastic neutron scattering spectroscopy. Neutron scattering also reveals the low-frequency rotational tunneling splitting, allowing estimation of the height of the torsional barrier for coordinated H{sub 2} rotating about its midpoint ({approximately}1 kcal/mol).

An attractive cis-effect of hydride on neighbor ligands: experimental and theoretical studies on the structure and intramolecular rearrangements of Fe(H)2(.eta.2-H2)(PEtPh2)3

Organometallic chalcogen complexes. XXIV. Synthesis, structure, and bonding of [Mo3(h5-C5H5)3S4]+[Sn(CH3)3Cl2]- containing a triangular molybdenum (IV) cluster cation with doubly and triply bridging sulfur atoms

The synthesis and characterization of derivatives of Mo(CO)(R 2 PC 2 H 4 PR 2 ) 2 (R=Et, i-Bu, Ph, Et-Ph) and their reactions with H 2 , N 2 , and SO 2 are reported. For R=Et and i-Bu, the H 2 oxidatively adds to give dihydrides, but for R=Ph, a η 2 -H 2 complex is formed. Electronic considerations, primarily back-bonding to H 2 σ * , are shown to be the primary cause of H-H bond cleavage.

Neutron structure and inelastic-neutron-scattering and theoretical studies of molybdenum complex Mo(CO)(H2)[(C6D5)2PC2H4P(C6D5)2]2.cntdot.4.5C6D6, a complex with an extremely low barrier to hydrogen rotation. Implications on the reaction coordinate for H-H cleavage to dihydride

Synthesis, characterization, and reactions of iron-sulfur clusters containing the S2 ligand: [Cp2Fe2(S2)(SR)2]0,1+, [Cp4Fe4S5]0,1+,2+, and [Cp4Fe4S6]

We have determined the crystal structure of ReO/sub 3/ at approx.15 kbar and 300 K well above the ''compressibility collapse'' transition (5.2 kbar, 300 K) with the use of the single-crystal diffractometer at the Los Alamos Pulsed Neutron Facility. Our data are consistent with space group Im3 and a = 7.41 (2) A. A model was refined to an R(F) value of 0.12. The octahedra are slightly rotated moving the oxygen atoms so as to form a 165/sup 0/ Re--O--Re angle. This structural model is consistent with a large body of recent physical data.

Phillip J. Vergamini

Papers

An attractive cis-effect of hydride on neighbor ligands: experimental and theoretical studies on the structure and intramolecular rearrangements of Fe(H)2(.eta.2-H2)(PEtPh2)3

Organometallic chalcogen complexes. XXIV. Synthesis, structure, and bonding of [Mo3(h5-C5H5)3S4]+[Sn(CH3)3Cl2]- containing a triangular molybdenum (IV) cluster cation with doubly and triply bridging sulfur atoms

Neutron structure and inelastic-neutron-scattering and theoretical studies of molybdenum complex Mo(CO)(H2)[(C6D5)2PC2H4P(C6D5)2]2.cntdot.4.5C6D6, a complex with an extremely low barrier to hydrogen rotation. Implications on the reaction coordinate for H-H cleavage to dihydride

Synthesis, characterization, and reactions of iron-sulfur clusters containing the S2 ligand: [Cp2Fe2(S2)(SR)2]0,1+, [Cp4Fe4S5]0,1+,2+, and [Cp4Fe4S6]

Structure of ReO/sub 3/ above the ''compressibility collapse'' transition