Biasing reaction pathways with mechanical force.

During the course of chemical reactions, reactant molecules need to surmount an energy barrier to allow their transformation into products. The energy needed for this process is usually provided by heat, light, pressure or electrical potential, which act either by changing the distribution of the reactants on their ground-state potential energy surface or by moving them onto an excited-state potential energy surface and thereby facilitate movement over the energy barrier. A fundamentally different way of initiating or accelerating a reaction is the use of force to deform reacting molecules along a specific direction of the reaction coordinate. Mechanical force has indeed been shown to activate covalent bonds in polymers, but the usual result is chain scission. Here we show that mechanically sensitive chemical groups make it possible to harness the mechanical forces generated when exposing polymer solutions to ultrasound, and that this allows us to accelerate rearrangement reactions and bias reaction pathways to yield products not obtainable from purely thermal or light-induced reactions. We find that when placed within long polymer strands, the trans and cis isomers of a 1,2-disubstituted benzocyclobutene undergo an ultrasound-induced electrocyclic ring opening in a formally conrotatory and formally disrotatory process, respectively, that yield identical products. This contrasts with reaction initiation by light or heat alone, in which case the isomers follow mutually exclusive pathways to different products. Mechanical forces associated with ultrasound can thus clearly alter the shape of potential energy surfaces so that otherwise forbidden or slow processes proceed under mild conditions, with the directionally specific nature of mechanical forces providing a reaction control that is fundamentally different from that achieved by adjusting chemical or physical parameters. Because rearrangement in our system occurs before chain scission, the effect we describe might allow the development of materials that are activated by mechanical stress fields.

Coordination chemistry of the soft chiral Lewis acid [Cp*Ir(TsDPEN)]+.

The paper surveys the binding of anions to the unsaturated 16e Lewis acid [Cp*Ir(TsDPEN)](+) ([1H](+)), where TsDPEN is racemic H(2)NCHPhCHPhNTs(-). The derivatives Cp*IrX(TsDPEN) were characterized crystallographically for X(-) = CN(-), Me(C═NH)S(-), NO(2)(-), 2-pyridonate, and 0.5 MoS(4)(2-). [(1H)(2)(µ-CN)](+) forms from [1H](+) and 1H(CN). Aside from 2-pyridone, amides generally add reversibly and bind to Ir through N. Thioacetamide binds irreversibly through sulfur. Compounds of the type Cp*IrX(TsDPEN) generally form diastereoselectively, although diastereomeric products were observed for the strong ligands (X = CN(-), H(-) (introduced via BH(4)(-)), or Me(C═NH)S(-)). Related experiments on the reaction (p-cymene)Ru(TsDPEN-H) + BH(4)(-) gave two diastereomers of (p-cymene)RuH(TsDPEN), the known hydrogenation catalyst and a second isomer that hydrogenated acetophenone more slowly. These experiment provide new insights into the enantioselectivity of these catalysts. Diastereomerization in all cases was first order in metal with modest solvent effects. The diphenyl groups are generally diequatorial for the stable diastereomers. For the 2-pyridonate adduct, axial phenyl groups are stabilized in the solid state by puckering of the IrN(2)C(2) ring induced by intramolecular hydrogen-bonding. Crystallographic analysis of [Cp*Ir(TsDPEN)](2)(MoS(4)) revealed a unique example of a κ(1),κ(1)-tetrathiometallate ligand. Cp*Ir(SC(NH)Me)TsDPEN) is the first example of a κ(1)-S-thioamidato complex.

Role of the azadithiolate cofactor in models for [FeFe]-hydrogenase: novel structures and catalytic implications.

This paper summarizes studies on the redox behavior of synthetic models for the [FeFe]-hydrogenases, consisting of diiron dithiolato carbonyl complexes bearing the amine cofactor and its N-benzyl derivative. Of specific interest are the causes of the low reactivity of oxidized models toward H(2), which contrasts with the high activity of these enzymes for H(2) oxidation. The redox and acid-base properties of the model complexes [Fe(2)[(SCH(2))(2)NR](CO)(3)(dppv)(PMe(3))](+) ([2](+) for R = H and [2'](+) for R = CH(2)C(6)H(5), dppv = cis-1,2-bis(diphenylphosphino)ethylene)) indicate that addition of H(2) followed by deprotonation are (i) endothermic for the mixed valence (Fe(II)Fe(I)) state and (ii) exothermic for the diferrous (Fe(II)Fe(II)) state. The diferrous state is shown to be unstable with respect to coordination of the amine to Fe, a derivative of which was characterized crystallographically. The redox and acid-base properties for the mixed valence models differ strongly for those containing the amine cofactor versus those derived from propanedithiolate. Protonation of [2'](+) induces disproportionation to a 1:1 mixture of the ammonium [H2'](+) (Fe(I)Fe(I)) and the dication [2'](2+) (Fe(II)Fe(II)). This effect is consistent with substantial enhancement of the basicity of the amine in the Fe(I)Fe(I) state vs the Fe(II)Fe(I) state. The Fe(I)Fe(I) ammonium compounds are rapid and efficient H-atom donors toward the nitroxyl compound TEMPO. The atom transfer is proposed to proceed via the hydride. Collectively, the results suggest that proton-coupled electron-transfer pathways should be considered for H(2) activation by the [FeFe]-hydrogenases.

Achieving unbiased predictions of national-scale groundwater redox conditions via data oversampling and statistical learning.

An important policy consideration for integrated land and water management is to understand the spatial distribution of nitrate attenuation in the groundwater system, for which redox condition is the key indicator. This paper proposes a methodology to accommodate the computational demands of large datasets, and presents national-scale predictions of groundwater redox class for New Zealand. Our approach applies statistical learning methods to relate the redox class determined on groundwater samples to spatially varying attributes. The trained model uses these spatial variables to predict redox status in areas without sample data. We assembled the groundwater sample data from regional authority databases, and assigned each sample a redox class. A key achievement was to overcome the influence of sample selection bias on model training via oversampling. We removed additional bias imposed by imbalances in the predictor variables by applying a conditional inference random forest classifier. The unbiased trained model uses eight predictors, and achieves a high validation performance (accuracy 0.81, kappa 0.71), providing good confidence in model predictions. National maps are provided for redox class and probability at specified depths. Feature importance rankings indicate that reducing conditions are associated with poorly-drained soils, and to a lesser extent, high hydrological variability, low elevation, and low-permeability lithology. These conditions are common in New Zealand's coastal and lowland plains, where artificial drainage is required to make land suitable for production. The spatial extent of reduced groundwater increases with depth, suggesting a shallow influence of soil infiltration or mobile organic carbon, and a deeper influence of lithological electron donors. Our model provides unbiased predictions at a scale relevant for environmental policy development and legislation. Identifying where the ecosystem service provided by denitrification can be utilised will enable spatially targeted interventions that can achieve the desired environmental outcome in a more cost-effective manner than non-targeted interventions.

Coordination chemistry of [HFe(CN)(2)(CO)(3)](-) and its derivatives: toward a model for the iron subsite of the [NiFe]-hydrogenases.

The photoreaction of Fe(CO)(5) and cyanide salts in MeCN solution affords the dianion [Fe(CN)(2)(CO)(3)](2-), conveniently isolated as [K(18-crown-6)](2)[Fe(CN)(2)(CO)(3)]. Solutions of [Fe(CN)(2)(CO)(3)](2-) oxidize irreversibly at -600 mV (vs Ag/AgCl) to give primarily [Fe(CN)(3)(CO)(3)](-). Protonation of the dianion affords the hydride [K(18-crown-6)][HFe(CN)(2)(CO)(3)] with a pK(a) approximately 17 (MeCN). The ferrous hydride exhibits enhanced electrophilicity vs its dianionic precursor, which resists substitution. Treatment of [K(18-crown-6)][Fe(CN)(2)(CO)(3)] with tertiary phosphines and phosphites gives isomeric mixtures of [HFe(CN)(2)(CO)(2)L](-) (L = P(OPh)(3) and PPh(3)). Carbonyl substitution on [1H(CO)(2)](-) by P(OPh)(3) is first-order in both the phosphite and iron (k = 0.18 M(-1) s(-1) at 22 degrees C) with DeltaH(double dagger) = 51.6 kJ mol(-1) and DeltaS(double dagger) = -83.0 J K(-1) mol(-1). These ligands are displaced under an atmosphere of CO. With cis-Ph(2)PCH=CHPPh(2) (dppv), we obtained the monocarbonyl, [HFe(CN)(2)(CO)(dppv)](-), a highly basic hydride (pK(a) > 23.3) that rearranges in solution to a single isomer. Treatment of [K(18-crown-6)][HFe(CN)(2)(CO)(3)] with Et(4)NCN resulted in rapid deprotonation to give [Fe(CN)(2)(CO)(3)](2-) and HCN. The tricyano hydride [HFe(CN)(3)(CO)(2)](2-) is prepared by the reaction of [HFe(CN)(2)(CO)(2)(PPh(3))](-) and [K(18-crown-6)]CN. Similar to the phosphine and phosphite derivatives, [HFe(CN)(3)(CO)(2)](2-) exists as a mixture of all three possible isomers. Protonation of the hydrides [HFe(CN)(2)(CO)(dppv)](-) and [HFe(CN)(3)(CO)(2)](-) in acetonitrile solutions releases H(2) and gives the corresponding acetonitrile complexes [K(18-crown-6)][Fe(CN)(3)(NCMe)(CO)(2)] and Fe(CN)(2)(NCMe)(CO)(dppv). Alkylation of [K(18-crown-6)](2)[Fe(CN)(2)(CO)(3)] with MeOTf gives the thermally unstable [MeFe(CN)(2)(CO)(3)](-), which was characterized spectroscopically at -40 degrees C. Reaction of dppv with [MeFe(CN)(2)(CO)(3)](-) gives the acetyl complex, [Fe(CN)(2)(COMe)(CO)(dppv)](-). Whereas [Fe(CN)(2)(CO)(3)](2-) undergoes protonation and methylation at Fe, acid chlorides give the iron(0) N-acylisocyanides [Fe(CN)(CO)(3)(CNCOR)](-) (R = Ph, CH(3)). The solid state structures of [K(18-crown-6)][HFe(CN)(2)(CO)(dppv)], Fe(CN)(2)(NCMe)(CO)(dppv), and [K(18-crown-6)](2)[HFe(CN)(3)(CO)(2)] were confirmed crystallographically. In all three cases, the cyanide ligands are cis to the hydride or acetonitrile ligands.

Redox activation of alkene ligands in platinum complexes with non-innocent ligands.

The reactivity of metal olefin complexes with non-innocent ligands (NILs) was examined. Treatment of PtCl(2)(diene) with the deprotonated catechol or aminophenol ligands afforded the corresponding Pt(NIL)(diene) complexes. The Pt((t)BA(F)Ph)(COD), Pt((t)BA(F)Ph)(nbd), and Pt(O(2)C(6)H(2)(t)Bu(2))(COD) (H(2)(t)BA(F)Ph = 2-(2-trifluoromethyl)anilino-4,6-di-tert-butylphenol, H(2)O(2)C(6)H(2)(t)Bu(2) = 3,5-di-tert-butylcatechol) complexes were examined by cyclic voltammetry. Treatment of Pt((t)BA(F)Ph)(COD) or Pt((t)BA(F)Ph)(nbd) with AgPF(6) afforded the imino-semiquinones [Pt((t)BA(F)Ph)(COD)]PF(6) or [Pt((t)BA(F)Ph)(nbd)]PF(6), respectively. The [Pt((t)BA(F)Ph)(COD)] complex was unreactive toward nucleophiles, whereas the oxidized derivative, [Pt((t)BA(F)Ph)(COD)]PF(6), rapidly and stereospecifically added alkoxides at the carbon trans to the phenolate. The Pt((t)BA(F)Ph)(COD), [Pt((t)BA(F)Ph)(COD)]PF(6), Pt((t)BA(F)Ph)(C(8)H(12)OMe), and [Cp(2)Co][Pt((t)BA(F)Ph)(C(8)H(12)OMe)] complexes were characterized crystallographically.

Diiron dithiolato carbonyls related to the H(ox)CO state of [FeFe]-hydrogenase.

Oxidation of the electron-rich (E(1/2) = -175 vs Ag/AgCl) ethanedithiolato complex Fe2(S2C2H4)(CO)2(dppv)2 (1) under a CO atmosphere yielded [Fe2(S2C2H4)(mu-CO)(CO)2(dppv)2](+) ([1(CO)](+)), a model for the H(ox)(CO) state of the [FeFe]-hydrogenases. This complex exists as two isomers: a kinetically favored unsymmetrical derivative, unsym-[1(CO)](+), and a thermodynamically favored isomer, sym-[1(CO)](+), wherein both diphosphines span apical and basal sites. Crystallographic characterization of sym-[1(CO)](+) confirmed a C2-symmetric structure with a bridging CO ligand and an elongated Fe-Fe bond of 2.7012(14) A, as predicted previously. Oxidation of sym-[1(CO)](+) and unsym-[1(CO)](+) again by 1e(-) oxidation afforded the respective diamagnetic diferrous derivatives where the relative stabilities of the sym and unsym isomers are reversed. DFT calculations indicate that the stabilities of sym and unsym isomers are affected differently by the oxidation state of the diiron unit: the mutually trans CO ligands in the sym isomer are more destabilizing in the mixed-valence state than in the diferrous state. EPR analysis of mixed-valence complexes revealed that, for [1](+), the unpaired spin is localized on a single iron center, whereas for unsym/sym-[1(CO)](+), the unpaired spin was delocalized over both iron centers, as indicated by the magnitude of the hyperfine coupling to the phosphine ligands trans to the Fe-Fe vector. Oxidation of 1 by 2 equiv of acetylferrocenium afforded the dication [1](2+), which, on the basis of low-temperature IR spectrum, is structurally similar to [1](+). Treatment of [1](2+) with CO gives unsym-[1(CO)](2+).

Nitrosyl derivatives of diiron(I) dithiolates mimic the structure and Lewis acidity of the [FeFe]-hydrogenase active site.

This study probes the impact of electronic asymmetry of diiron(I) dithiolato carbonyls. Treatment of Fe2(S2C(n)H(2n))(CO)(6-x)(PMe3)x compounds (n = 2, 3; x = 1, 2, 3) with NOBF4 gave the derivatives [Fe2(S2C(n)H(2n))(CO)(5-x)(PMe3)x(NO)]BF4, which are electronically unsymmetrical because of the presence of a single NO(+) ligand. Whereas the monophosphine derivative is largely undistorted, the bis(PMe3) derivatives are distorted such that the CO ligand on the Fe(CO)(PMe3)(NO)(+) subunit is semibridging. Two isomers of [Fe2(S2C3H6)(CO)3(PMe3)2(NO)]BF4 were characterized spectroscopically and crystallographically. Each isomer features electron-rich Fe(CO)2PMe3 and electrophilic Fe(CO)(PMe3)(NO)(+) subunits. These species are in equilibrium with an unobserved isomer that reversibly binds CO (DeltaH = -35 kJ/mol, DeltaS = -139 J mol(-1) K(-1)) to give the symmetrical adduct [Fe2(S2C3H6)(mu-NO)(CO)4(PMe3)2]BF4. In contrast to Fe2(S2C3H6)(CO)4(PMe3)2, the bis(PMe3) nitrosyl complexes readily undergo CO substitution to give the (PMe3)3 derivatives. The nitrosyl complexes reduce at potentials that are approximately 1 V milder than their carbonyl counterparts. Results of density functional theory calculations, specifically natural bond orbital analysis, reinforce the electronic resemblance of the nitrosyl complexes to the corresponding mixed-valence diiron complexes. Unlike other diiron dithiolato carbonyls, these species undergo reversible reductions at mild potentials. The results show that the novel structural and chemical features associated with mixed-valence diiron dithiolates (the so-called H(ox) models) can be replicated in the absence of mixed-valency by the introduction of electronic asymmetry.

Covalent surface modification of a metal-organic framework: selective surface engineering via Cu(I)-catalyzed Huisgen cycloaddition.

A Zn-cornered, mixed-ligand, metal-organic framework (MOF) bearing TMS-protected acetylenes has been constructed and its surface decorated with organic molecules via'click chemistry', in a demonstration of selective post-synthesis functionalization.

Redox and structural properties of mixed-valence models for the active site of the [FeFe]-hydrogenase: progress and challenges.

The one-electron oxidations of a series of diiron(I) dithiolato carbonyls were examined to evaluate the factors that affect the oxidation state assignments, structures, and reactivity of these low-molecular weight models for the H ox state of the [FeFe]-hydrogenases. The propanedithiolates Fe 2(S 2C 3H 6)(CO) 3(L)(dppv) (L = CO, PMe 3, P i-Pr 3) oxidize at potentials approximately 180 mV milder than the related ethanedithiolates ( Angew. Chem., Int. Ed. 2007, 46, 6152). The steric clash between the central methylene of the propanedithiolate and the phosphine favors the rotated structure, which forms upon oxidation. Electron Paramagnetic Resonance (EPR) spectra for the mixed-valence cations indicate that the unpaired electron is localized on the Fe(CO)(dppv) center in both [Fe 2(S 2C 3H 6)(CO) 4(dppv)]BF 4 and [Fe 2(S 2C 3H 6)(CO) 3(PMe 3)(dppv)]BF 4, as seen previously for the ethanedithiolate [Fe 2(S 2C 2H 4)(CO) 3(PMe 3)(dppv)]BF 4. For [Fe 2(S 2C n H 2 n )(CO) 3(P i-Pr 3)(dppv)]BF 4; however, the spin is localized on the Fe(CO) 2(P i-Pr 3) center, although the Fe(CO)(dppv) site is rotated in the crystalline state. IR and EPR spectra, as well as redox potentials and density-functional theory (DFT) calculations, suggest that the Fe(CO) 2(P i-Pr 3) site is rotated in solution, driven by steric factors. Analysis of the DFT-computed partial atomic charges for the mixed-valence species shows that the Fe atom featuring a vacant apical coordination position is an electrophilic Fe(I) center. One-electron oxidation of [Fe 2(S 2C 2H 4)(CN)(CO) 3(dppv)] (-) resulted in 2e oxidation of 0.5 equiv to give the mu-cyano derivative [Fe (I) 2(S 2C 2H 4)(CO) 3(dppv)](mu-CN)[Fe (II) 2(S 2C 2H 4)(mu-CO)(CO) 2(CN)(dppv)], which was characterized spectroscopically.

Precursors to [FeFe]-hydrogenase models: syntheses of Fe2(SR)2(CO)6 from CO-free iron sources.

This report describes routes to iron dithiolato carbonyls that do not require preformed iron carbonyls. The reaction of FeCl 2, Zn, and Q 2S 2C n H 2 n (Q (+) = Na (+), Et 3NH (+)) under an atmosphere of CO affords Fe 2(S 2C n H 2 n )(CO) 6 ( n = 2, 3) in yields >70%. The method was employed to prepare Fe 2(S 2C 2H 4)( (13)CO) 6. Treatment of these carbonylated mixtures with tertiary phosphines, instead of Zn, gave the ferrous species Fe 3(S 2C 3H 6) 3(CO) 4(PR 3) 2, for R = Et, Bu, and Ph. Like the related complex Fe 3(SPh) 6(CO) 6, these compounds consist of a linear arrangement of three conjoined face-shared octahedral centers. Omitting the phosphine but with an excess of dithiolate, we obtained the related mixed-valence triiron species [Fe 3(S 2C n H 2 n ) 4(CO) 4] (-). The highly reducing all-ferrous species [Fe 3(S 2C n H 2 n ) 4(CO) 4] (2-) is implicated as an intermediate in this transformation. Reactive forms of iron, prepared by the method of Rieke, also combined with dithiols under a CO atmosphere to give Fe 2(S 2C n H 2 n )(CO) 6 in modest yields under mild conditions. Studies on the order of addition indicate that ferrous thiolates are formed prior to the onset of carbonylation. Crystallographic characterization demonstrated that the complexes Fe 3(S 2C 3H 6) 3(CO) 4(PEt 3) 2 and PBnPh 3[Fe 3(S 2C 3H 6) 4(CO) 4] feature high-spin ferrous and low-spin ferric as the central metal, respectively.

New nitrosyl derivatives of diiron dithiolates related to the active site of the [FeFe]-hydrogenases.

Nitrosyl derivatives of diiron dithiolato carbonyls have been prepared starting from the precursor Fe(2)(S(2)C(n)H(2n))(dppv)(CO)(4) (dppv = cis-1,2-bis(diphenylphosphinoethylene). These studies expand the range of substituted diiron(I) dithiolato carbonyl complexes. From [Fe(2)(S(2)C(2)H(4))(CO)(3)(dppv)(NO)]BF(4) ([1(CO)(3)]BF(4)), the following compounds were prepared: [1(CO)(2)(PMe(3))]BF(4), [1(CO)(dppv)]BF(4), NEt(4)[1(CO)(CN)(2)], and 1(CO)(CN)(PMe(3)). Some of these substitution reactions occur via the addition of 2 equiv of the nucleophile followed by the dissociation of one nucleophile and decarbonylation. Such a double adduct was characterized crystallographically in the case of [Fe(2)(S(2)C(2)H(4))(CO)(3)(dppv)(NO)(PMe(3))(2)]BF(4). This result shows that the addition of two ligands causes scission of the Fe-Fe bond and one Fe-S bond. When cyanide is the nucleophile, nitrosyl migrates away from the Fe(dppv) site, yielding a Fe(CN)(2)(NO) derivative. Compounds [1(CO)(3)]BF(4), [1(CO)(2)(PMe(3))]BF(4), and [1(CO)(dppv)]BF(4) were also prepared by the addition of NO(+) to the di-, tri-, and tetrasubstituted precursors. In these cases, the NO(+) appears to form an initial 36e(-) adduct containing terminal Fe-NO, followed by decarbonylation. Several complexes were prepared by the addition of NO to the mixed-valence Fe(I)Fe(II) derivatives. The diiron nitrosyl complexes reduce at mild potentials and in certain cases form weak adducts with CO. IR and EPR spectra of 1(CO)(dppv), generated by low-temperature reduction of [1(CO)(dppv)]BF(4) with Co(C(5)Me(5))(2), indicates that the SOMO is located on the FeNO subunit.

Quantifying River-Groundwater Interactions of New Zealand's Gravel-Bed Rivers: The Wairau Plain.

New Zealand's gravel-bed rivers have deposited coarse, highly conductive gravel aquifers that are predominantly fed by river water. Managing their groundwater resources is challenging because the recharge mechanisms in these rivers are poorly understood and recharge rates are difficult to predict, particularly under a more variable future climate. To understand the river-groundwater exchange processes in gravel-bed rivers, we investigate the Wairau Plain Aquifer using a three-dimensional groundwater flow model which was calibrated using targeted field observations, "soft" information from experts of the local water authority, parameter regularization techniques, and the model-independent parameter estimation software PEST. The uncertainty of simulated river-aquifer exchange flows, groundwater heads, spring flows, and mean transit times were evaluated using Null-space Monte-Carlo methods. Our analysis suggests that the river is hydraulically perched (losing) above the regional water table in its upper reaches and is gaining downstream where marine sediments overlay unconfined gravels. River recharge rates are on average 7.3 m3 /s, but are highly dynamic in time and variable in space. Although the river discharge regularly hits 1000 m3 /s, the net exchange flow rarely exceeds 12 m3 /s and seems to be limited by the physical constraints of unit-gradient flux under disconnected rivers. An important finding for the management of the aquifer is that changes in aquifer storage are mainly affected by the frequency and duration of low-flow periods in the river. We hypothesize that the new insights into the river-groundwater exchange mechanisms of the presented case study are transferable to other rivers with similar characteristics.

Crystal polymorphism of protein GB1 examined by solid-state NMR spectroscopy and X-ray diffraction.

The study of micro- or nanocrystalline proteins by magic-angle spinning (MAS) solid-state NMR (SSNMR) gives atomic-resolution insight into structure in cases when single crystals cannot be obtained for diffraction studies. Subtle differences in the local chemical environment around the protein, including the characteristics of the cosolvent and the buffer, determine whether a protein will form single crystals. The impact of these small changes in formulation is also evident in the SSNMR spectra; however, the changes lead only to correspondingly subtle changes in the spectra. Here, we demonstrate that several formulations of GB1 microcrystals yield very high quality SSNMR spectra, although only a subset of conditions enable growth of single crystals. We have characterized these polymorphs by X-ray powder diffraction and assigned the SSNMR spectra. Assignments of the 13C and 15N SSNMR chemical shifts confirm that the backbone structure is conserved, indicative of a common protein fold, but side chain chemical shifts are changed on the surface of the protein, in a manner dependent upon crystal packing and electrostatic interactions with salt in the mother liquor. Our results demonstrate the ability of SSNMR to reveal minor structural differences among crystal polymorphs. This ability has potential practical utility for studying the formulation chemistry of industrial and therapeutic proteins, as well as for deriving fundamental insights into the phenomenon of single-crystal growth.

Improved distribution of small molecules and viral vectors in the murine brain using a hollow fiber catheter.

OBJECT: A hollow fiber catheter was developed to improve the distribution of drugs administered via direct infusion into the central nervous system (CNS). It is a porous catheter that significantly increases the surface area of brain tissue into which a drug is infused. METHODS: Dye was infused into the mouse brain through convection-enhanced delivery (CED) using a 28-gauge needle compared with a 3-mm-long hollow fiber catheter. To determine whether a hollow fiber catheter could increase the distribution of gene therapy vectors, a recombinant adenovirus expressing the firefly luciferase reporter was injected into the mouse striatum. Gene expression was monitored using in vivo bioluminescent imaging. To assess the distribution of gene transfer, an adenovirus expressing green fluorescent protein was injected into the striatum using a hollow fiber catheter or a needle. RESULTS: Hollow fiber catheter-mediated infusion increased the volume of brain tissue labeled with dye by 2.7 times relative to needle-mediated infusion. In vivo imaging revealed that catheter-mediated infusion of adenovirus resulted in gene expression that was 10-times greater than that mediated by a needle. The catheter appreciably increased the area of brain transduced with adenovirus relative to a needle, affecting a significant portion of the injected hemisphere. CONCLUSIONS: The miniature hollow fiber catheter used in this study significantly increased the distribution of dye and adenoviral-mediated gene transfer in the mouse brain compared with the levels reached using a 28-gauge needle. Compared with standard single-port clinical catheters, the hollow fiber catheter has the advantage of millions of nanoscale pores to increase surface area and bulk flow in the CNS. Extending the scale of the hollow fiber catheter for the large mammalian brain shows promise in increasing the distribution and efficacy of gene therapy and drug therapy using CED.

X-ray Crystallographic Evidence in Support of a Proposed Chiral Recognition Mechanism.

A new family of pi-basic chiral selectors has been developed and employed in the separation of enantiomers by liquid chromatography. These chiral selectors, derived from (S)-proline and designed from mechanistic considerations, show high levels of discrimination between the enantiomers of N-(3,5-dinitrobenzoyl)amino acid esters and amides. A considerable amount of chromatographic data has been assembled, all of it consistent with the proposed chiral recognition mechanism. Moreover, this mechanism is supported by induced chemical shift differences and intermolecular NOE data previously obtained in solution with an equimolar mixture of (S)-1 and (S)-2. A crystalline 1:1 complex of (S)-1 and (S)-2 has been obtained and analyzed by X-ray crystallography. The structure of this complex in the solid state illustrates the essential features of the mechanism proposed to account for chiral recognition between chiral stationary phase (CSP) 3 and the enantiomers of 2 and related analytes. In addition, the orientation of the two components in the solid state is in close agreement with the structure of the more stable diastereomeric complex deduced from solution-state NMR evidence relating to the same system.

Synthesis, Characterization, and Comparative Properties of [PPN](2)[Re(6)C(CO)(18)Mo(CO)(4)] and [PPN](2)[Re(6)C(CO)(18)Ru(CO)(3)].

The reaction of [PPN](2)[Re(6)C(CO)(19)] with Mo(CO)(6) and Ru(3)(CO)(12) under sunlamp irradiation provided the new mixed-metal clusters [PPN](2)[Re(6)C(CO)(18)Mo(CO)(4)] and [PPN](2)[Re(6)C(CO)(18)Ru(CO)(3)], which were isolated in yields of 85% and 61%, respectively. The compound [PPN](2)[Re(6)C(CO)(18)Mo(CO)(4)] crystallizes in the monoclinic space group P2(1)/c with a = 20.190 (7) Å, b = 16.489 (7) Å, c = 27.778 (7) Å, beta = 101.48 (2) degrees, and Z = 4 (at T = -75 degrees C). The cluster anion is composed of a Re(6)C octahedral core with a face capped by a Mo(CO)(4) fragment. There are three terminal carbonyl ligands coordinated to each rhenium atom. The four carbonyl ligands on the molybdenum center are essentially terminal, with one pair of carbonyl ligands (C72-O72 and C74-O74) subtending a relatively large angle at molybdenum (C72-Mo-C74 = 147.2(9) degrees ), whereas the remaining pair of carbonyl ligands (C71-O71 and C73-O73) subtend a much smaller angle (C71-Mo-C73 = 100.5(9) degrees ). The (13)C NMR spectrum of (13)CO-enriched [PPN](2)[Re(6)C(CO)(18)Mo(CO)(4)] shows signals for four sets of carbonyl ligands at -40 degrees C, consistent with the solid state structure, but the carbonyl ligands undergo complete scrambling at ambient temperature. The (13)C NMR spectrum of (13)CO-enriched [PPN](2)[Re(6)C(CO)(18)Ru(CO)(3)] at 20 degrees C is consistent with the expected structure of an octahedral Re(6)C(CO)(18) core capped by a Ru(CO)(3) fragment. The visible spectrum of [PPN](2)[Re(6)C(CO)(18)Mo(CO)(4)] shows a broad, strong band at 670 nm (epsilon = 8100), whereas all of the absorptions of [PPN](2)[Re(6)C(CO)(18)Ru(CO)(3)] are at higher energy. An irreversible oxidation wave with E(p) at 0.34 V is observed for [PPN](2)[Re(6)C(CO)(18)Mo(CO)(4)], whereas two quasi-reversible oxidation waves with E(1/2) values of 0.21 and 0.61 V (vs Ag/AgCl) are observed for [PPN](2)[Re(6)C(CO)(18)Ru(CO)(3)]. The molybdenum cap in [Re(6)C(CO)(18)Mo(CO(4))](2-) is cleaved by heating in donor solvents, and by treatment with H(2), to give largely [H(2)Re(6)C(CO)(18)](2-). In contrast, [Re(6)C(CO)(18)Ru(CO)(3)](2-) shows no tendency to react under similar conditions.

Coordination Networks of 3,3'-Dicyanodiphenylacetylene and Silver(I) Salts: Structural Diversity through Changes in Ligand Conformation and Counterion.

Coordination networks of 3,3'-dicyanodiphenylacetylene (3,3'-DCPA, 1) with silver(I) salts characterized by single-crystal X-ray analysis are described. Network topology is found to depend on both the counterion and solvent employed during crystallization. The conformation adopted by the ligand varies between planar cisoid and planar transoid. With silver(I) triflate (AgCF(3)SO(3)) in benzene, a sheet structure of composition [Ag(1)CF(3)SO(3)]C(6)H(6) (2) forms in which silver(I) is five-coordinate and bonds to two nitrogen atoms of distinct 3,3'-DCPA molecules, another silver(I) ion, and two oxygen atoms of the triflate ions. Changing the solvent to toluene produces an undulating sheet structure of composition [Ag(2)(1)(CF(3)SO(3))(2)] (3) in which silver(I) is six-coordinate, bonding to a ligand nitrogen atom, to four oxygen atoms of bridging triflate ions, and to a neighboring silver(I) ion. In both triflate structures, 3,3'-DCPA adopts a transoid conformation with respect to the positioning of the nitrile groups. With silver(I) hexafluorophosphate (AgPF(6)), silver(I) hexafluoroarsenate (AgAsF(6)), or silver(I) hexafluoroantimonate (AgSbF(6)), 2-fold interpenetrated sheet structures [Ag(1)(2)]XF(6) (X = P (4), As (5), or Sb (6)) are obtained in which 3,3'-DCPA coordinates to tetrahedral silver(I) ions in a cisoid conformation. In spite of the large difference in counterion size, minimal network deformation is observed among these systems. Interestingly, with silver(I) perchlorate hydrate (AgClO(4).xH(2)O, x approximately 1), 3,3'-DCPA coordinates in a transoid conformation to tetrahedral silver(I) ions to form the 8-fold interpenetrated diamondoid network [Ag(1)(2)]ClO(4).H(2)O (7). An analysis of the packing of these networks is provided, and the results are compared to complementary systems previously reported from our study of coordination networks of dinitriles and silver(I) salts.

Synthesis and Properties of IrRe(2)(&mgr;-H)(2)(CO)(9)(eta(5)-C(9)H(7)).

The slow addition of Re(2)(&mgr;-H)(2)(CO)(8) to a solution of Ir(CO)(eta(2)-C(8)H(14))(eta(5)-C(9)H(7)) in hexane at reflux provides IrRe(2)(&mgr;-H)(2)(CO)(9)(eta(5)-C(9)H(7)) (1) in 80% yield. The molecular structure of 1 shows an IrRe(2) triangle incorporating one Ir(CO)(eta(5)-C(9)H(7)) and two Re(CO)(4) fragments. The strongly different Ir-Re distances suggest that one hydride ligand bridges one Ir-Re edge and the other hydride bridges the Re-Re edge. Low-temperature (1)H and (13)C NMR spectra are consistent with this structure; at higher temperatures a dynamic process involving migration of one hydride ligand between the two Ir-Re edges is observed. Cluster 1 is readily deprotonated with KOH/EtOH, and the resulting anion has been isolated as the PPN salt, [PPN][IrRe(2)(&mgr;-H)(CO)(9)(eta(5)-C(9)H(7))] (2). Both the (1)H and low temperature (13)C NMR spectra of 2 are consistent with a structure in which the remaining hydride ligand bridges the Re-Re edge. Variable-temperature (13)C NMR spectra indicate that 2 undergoes CO scrambling localized on the Ir-Re edges. The reaction of 1 with PPh(3) leads to IrRe(2)(&mgr;-H)(2)(CO)(8)(PPh(3))(eta(5)-C(9)H(7)) (3), which contains the phosphine on a rhenium atom, as well as to cluster fragmentation.

Solution and Solid-State Studies of a Chiral Zinc-Sulfonamide Complex Relevant to Enantioselective Cyclopropanations.

A highly distorted tetrahedron formed by the four nitrogen atoms around zinc in the crystalline zinc-sulfonamide complex 1 may explain its catalytic activity in asymmetric cyclopropanations. The agent is formed by deprotonation of (R,R)-N,N'-cyclohexane-1,2-diyl)bis(n-butanesulfonamide) with diethylzinc and addition of 2,2'-bipyridyl.