Synthesis and characterization of model compounds of the lysine tyrosyl quinone cofactor of lysyl oxidase

4-n-Butylamino-5-ethyl-1,2-benzoquinone (1(ox)) has been synthesized as a model compound for the LTQ (lysine tyrosyl quinone) cofactor of lysyl oxidase (LOX). At pH 7, 1(ox) has a lambda(max) at 504 nm and exists as a neutral o-quinone in contrast to a TPQ (2,4,5-trihydroxyphenylalanine quinone) model compound, 4, which is a resonance-stabilized monoanion. Despite these structural differences 1(ox) and 4 have the same redox potential (ca. -180 mV vs SCE). The structure of the phenylhydrazine adduct of 1(ox) (2) is reported, and 2D NMR spectroscopy has been used to show that the position of nucleophilic addition is at C(1). UV-vis spectroscopic pH titration of phenylhydrazine adducts of 1(ox) and 4, 2, and 11, respectively, reveals a similar red shift in lambda(max) at alkaline pH with the same pK(a) (approximately 11.8). In contrast, the red shift in lambda(max) at acidic pH conditions yields different pK(a) values (2.12 for 2 vs -0.28 for 11), providing a means to distinguish LTQ from TPQ. Reactions between in situ generated 4-ethyl-1,2-benzoquinone and primary amines give a mixture of products, indicating that the protein environment must play an essential role in LTQ biogenesis by directing the nucleophilic addition of the epsilon-amino group of a lysine residue to the C(4) position of a putative dopaquinone intermediate. Characterization of a 1,6-adduct between an o-quinone and butylamine (3-n-butylamino-5-ethyl-1,2-benzoquinone, 13) confirms the assignment of LTQ as a 1,4-addition product.     

Synthesis of phthalide derivatives using nickel-catalyzed cyclization of o-haloesters with aldehydes

The reaction of o-bromobenzoate (1 b) with benzaldehyde (2 a) in the presence of [NiBr(2)(dppe)] (dppe=1,2-bis(diphenylphosphino)ethane) and zinc powder in THF (24 hours, reflux temperature), afforded 3-phenyl-3H-isobenzofuran-1-one (3 a) in an 86 % yield. Similarly, o-iodobenzoate reacts with 2 a to give 3 a, but in a lower yield (50 %). A series of substituted aromatic and aliphatic aldehydes (2 b, 4-MeC(6)H(4)CHO; 2 c, 4-MeOC(6)H(4)CHO; 2 d, 3-MeOC(6)H(4)CHO; 2 e, 2-MeOC(6)H(4)CHO; 2 f, 4-CNC(6)H(4)CHO; 2 g, 4-(Me)(3)CC(6)H(4)CHO; 2 h, 4-C(6)H(5)C(6)H(4)CHO; 2 i, 4-ClC(6)H(4)CHO; 2 j, 4-CF(3)C(6)H(4)CHO; 2 k, CH(3)(CH(2))(5)CHO; 2 l, CH(3)(CH(2))(2)CHO) also underwent cyclization with o-bromobenzoate (1 b) producing the corresponding phthalide derivatives in moderate to excellent yields and with high chemoselectivity. Like 1 b, methyl 2-bromo-4,5-dimethoxybenzoate (1 c) reacts with tolualdehyde (2 b) to give the corresponding substituted phthalide 3 m in a 71 % yield. The methodology can be further applied to the synthesis of six-membered lactones. The reaction of methyl 2-(2-bromophenyl)acetate (1 d) with benzaldehyde under similar reaction conditions afforded six-membered lactone 3 o in a 68 % yield. A possible catalytic mechanism for this cyclization is also proposed.     

Rhenium oxo complexes of a chelating diyne ligand. Synthesis and study of the kinetics of protonation

A series of oxo complexes, Re(O)X(diyne) (X = I, Me, Et), have been prepared from 2,7-nonadiyne and Re(O)I(3)(PPh(3))(2). Addition of B(C(6)F(5))(3) to Re(O)I(2,7-nonadiyne) (5) results in coordination of the oxo ligand to the boron. The protonation of Re(O)(X)(2-butyne)(2) and Re(O)(X)(2,7-nonadiyne)(2) with a variety of acids has been examined. With 5 and HBF(4)/Et(2)O, the ultimate product was [Re(CH(3)CN)(3)(I)(2,7-nonadiyne)](2+) (7). The conversion of 5 to 7 changes the conformation of the diyne ligand from a "chair" to a "boat" and shifts its propargylic protons considerably downfield in the (1)H NMR. The kinetics of the protonation of Re(O)I(2,7-nonadiyne) (5) by CF(3)SO(3)H in CH(3)CN have been monitored by visible spectroscopy, in a stopped-flow apparatus, and by low temperature (1)H NMR. Two second-order rate constants, presumably successive protonations, were observed in the stopped-flow, k(1) = 11.9 M(-)(1) s(-)(1) and k(2) = 3.8 M(-)(1) s(-)(1). Low temperature (1)H NMR spectroscopy indicated that the resulting solution contained a mixture of two doubly protonated intermediates X and Y, each of which slowly formed the product 7 via an acid-independent process.     

Synthesis of monomeric Fe(II) and Ru(II) complexes of tetradentate phosphines

rac-Bis[{(diphenylphosphino)ethyl}-phenylphosphino]methane (DPPEPM) reacts with iron(II) and ruthenium(II) halides to generate complexes with folded DPPEPM coordination. The paramagnetic, five-coordinate Fe(DPPEPM)Cl(2) (1) in CD(2)Cl(2) features a tridentate binding mode as established by (31)P{(1)H} NMR spectroscopy. Crystal structure analysis of the analogous bromo complex, Fe(DPPEPM)Br(2) (2) revealed a pseudo-octahedral, cis-α geometry at iron with DPPEPM coordinated in a tetradentate fashion. However, in CD(2)Cl(2) solution, the coordination of DPPEPM in 2 is similar to that of 1 in that one of the external phosphorus atoms is dissociated resulting in a mixture of three tridentate complexes. The chloro ruthenium complex cis-Ru(κ(4)-DPPEPM)Cl(2) (3) is obtained from rac-DPPEPM and either [RuCl(2)(COD)](2) [COD = 1,5-cyclooctadiene] or RuCl(2)(PPh(3))(4). The structure of 3 in both the solid state and in CD(2)Cl(2) solution features a folded κ(4)-DPPEPM. This binding mode was also observed in cis-[Fe(κ(4)-DPPEPM)(CH(3)CN)(2)](CF(3)SO(3))(2) (4). Addition of an excess of CO to a methanolic solution of 1 results in the replacement of one of the chloride ions by CO to yield cis-[Fe(κ(4)-DPPEPM)Cl(CO)](Cl) (5). The same reaction in CH(2)Cl(2) produces a mixture of 5 and [Fe(κ(3)-DPPEPM)Cl(2)(CO)] (6) in which one of the internal phosphines has been substituted by CO. Complexes 2, 3, 4, and 5 appear to be the first structurally characterized monometallic complexes of κ(4)-DPPEPM.     

Modulation of the pK(a) of metal-bound water via oxidation of thiolato sulfur in model complexes of Co(III) containing nitrile hydratase: insight into possible effect of cysteine oxidation in Co-nitrile hydratase

The Co(III) complexes of N,N'-bis(2-mercaptophenyl)pyridine-2,6-dicarboxamide (PyPSH(4)), a designed pentadentate ligand with built-in carboxamide and thiolate groups, have been synthesized and studied to gain insight into the role of Cys-S oxidation in Co-containing nitrile hydratase (Co-NHase). Reaction of [Co(NH(3))(5)Cl]Cl(2) with PyPS(4)(-) in DMF affords the thiolato-bridged dimeric Co(III) complex (Et(4)N)(2)[Co(2)(PyPS)(2)] (1). Although the bridged structure is quite robust, reaction of (Et(4)N)(CN) with 1 in acetonitrile affords the monomeric species (Et(4)N)(2)[Co(PyPS)(CN)] (2). Oxidation of 2 with H(2)O(2) in acetonitrile gives rise to a mixture which, upon chromatographic purification, yields K(2)[Co(PyPSO(2)(OSO(2))(CN] (3), a species containing asymmetrically oxidized thiolates. The Co(III) metal center in 3 is coordinated to a S-bound sulfinate and an O-bound sulfonate (OSO(2)) group. Upon oxidation with H(2)O(2), 1 affords an asymmetrically oxidized dimer (Et(4)N)(2)[Co(2)(PyPS(SO(2)))(2)] (4) in which only the terminal thiolates are oxidized to form S-bound sulfinate groups while the bridging thiolates remain unchanged. The thiolato-bridge in 4 is also cleaved upon reaction with (Et(4)N)(CN) in acetonitrile, and one obtains (Et(4)N)(2)[Co(PyPS(SO(2)))(CN)] (5), a species that contains both coordinated thiolate and S-bound sulfinate around Co(III). The structures of 1-4 have been determined. The spectroscopic properties and reactivity of all the complexes have been studied to understand the behavior of the Co(III) site in Co-NHase. Unlike typical Co(III) complexes with bound CN(-) ligands, the Co(III) centers in 2 and 5 are labile and rapidly lose CN(-) in aqueous solutions. Since 3 does not show this lability, it appears that at least one thiolato sulfur donor is required in the first coordination sphere for the Co(III) center in such species to exhibit lability. Both 2 and 5 are converted to the aqua complexes [Co(PyPS)(H(2)O)](-) and [Co(PyPS(SO(2))(H(2)O)](-) in aqueous solutions. The pK(a) values of the bound water in these two species, determined by spectrophotometry, are 8.3 +/- 0.03 and 7.2 +/- 0.06, respectively. Oxidation of the thiolato sulfur (to sulfinate) therefore increases the acidity of the bound water. Since 2 and 5 promote hydrolysis of acetonitrile at pH values above their corresponding pK(a) values, it is also evident that a metal-bound hydroxide is a key player in the mechanism of hydrolysis by these model complexes of Co-NHase. The required presence of a Cys-sulfinic residue and one water molecule at the Co(III) site of Co-NHase as well as the optimal pH of the enzyme near 7 suggests that (i) modulation of the pK(a) of the bound water molecule at the active site of the enzyme could be one role of the oxidized Cys-S residue(s) and (ii) a cobalt-bound hydroxide could be responsible for the hydrolysis of nitriles by Co-NHase.     

Mechanism of reaction of hydrogen peroxide with horseradish peroxidase: identification of intermediates in the catalytic cycle.

The mechanism of the reaction of horseradish peroxidase isoenzyme C (HRPC) with hydrogen peroxide to form the reactive enzyme intermediate compound I has been studied using electronic absorbance, rapid-scan stopped-flow, and electron paramagnetic resonance (EPR) spectroscopies at both acid and basic pH. The roles of the active site residues His42 and Arg38 in controlling heterolytic cleavage of the H(2)O(2) oxygen-oxygen bond have been probed with site-directed mutant enzymes His42 --> Leu (H42L), Arg38 --> Leu (R38L), and Arg38 --> Gly (R38G). The biphasic reaction kinetics of H42L with H(2)O(2) suggested the presence of an intermediate species and, at acid pH, a reversible second step, probably due to a neutral enzyme-H(2)O(2) complex and the ferric-peroxoanion-containing compound 0. EPR also indicated the formation of a protein radical situated more than approximately 10 A from the heme iron. The stoichiometry of the reaction of the H42L/H(2)O(2) reaction product and 2,2'-azinobis(3-ethylbenzothiazolinesulfonic acid) (ABTS) was concentration dependent and fell from a value of 2 to 1 above 0.7 mM ABTS. These data can be explained if H(2)O(2) undergoes homolytic cleavage in H42L. The apparent rate of compound I formation by H42L, while low, was pH independent in contrast to wild-type HRPC where the rate falls at acid pH, indicating the involvement of an ionizable group with pK(a) approximately 4. In R38L and R38G, the apparent pK(a) was shifted to approximately 8 but there is no evidence that homolytic cleavage of H(2)O(2) occurs. These data suggest that His42 acts initially as a proton acceptor (base catalyst) and then as a donor (acid catalyst) at neutral pH and predict the observed slower rate and lower efficiency of heterolytic cleavage observed at acid pH. Arg38 is influential in lowering the pK(a) of His42 and additionally in aligning H(2)O(2) in the active site, but it does not play a direct role in proton transfer.     

Synthesis and reactivity of silyl ruthenium complexes: the importance of trans effects in C-H activation,Si-C bond formation,and dehydrogenative coupling of silanes

A series of octahedral ruthenium silyl hydride complexes, cis-(PMe(3))(4)Ru(SiR(3))H (SiR(3) = SiMe(3), 1a; SiMe(2)CH(2)SiMe(3), 1b; SiEt(3), 1c; SiMe(2)H, 1d), has been synthesized by the reaction of hydrosilanes with (PMe(3))(3)Ru(eta(2)-CH(2)PMe(2))H (5), cis-(PMe(3))(4)RuMe(2) (6), or (PMe(3))(4)RuH(2) (9). Reaction with 6 proceeds via an intermediate product, cis-(PMe(3))(4)Ru(SiR(3))Me (SiR(3) = SiMe(3), 7a; SiMe(2)CH(2)SiMe(3), 7b). Alternatively, 1 and 7 have been synthesized via a fast hydrosilane exchange with another cis-(PMe(3))(4)Ru(SiR(3))H or cis-(PMe(3))(4)Ru(SiR(3))Me, which occurs at a rate approaching the NMR time scale. Compounds 1a, 1b, 1d, and 7a adopt octahedral geometries in solution and the solid state with mutually cis silyl and hydride (or silyl and methyl) ligands. The longest Ru-P distance within a complex is always trans to Si, reflecting the strong trans influence of silicon. The aptitude of phosphine dissociation in these complexes has been probed in reactions of 1a, 1c, and 7a with PMe(3)-d(9) and CO. The dissociation is regioselective in the position trans to a silyl ligand (trans effect of Si), and the rate approaches the NMR time scale. A slower secondary process introduces PMe(3)-d(9) and CO in the other octahedral positions, most likely via nondissociative isomerization. The trans effect and trans influence in 7a are so strong that an equilibrium concentration of dissociated phosphine is detectable (approximately 5%) in solution of pure 7a. Compounds 1a-c also react with dihydrogen via regioselective dissociation of phosphine from the site trans to Si, but the final product, fac-(PMe(3))(3)Ru(SiR(3))H(3) (SiR(3) = SiMe(3), 4a; SiMe(2)CH(2)SiMe(3), 4b; SiEt(3), 4c), features hydrides cis to Si. Alternatively, 4a-c have been synthesized by photolysis of (PMe(3))(4)RuH(2) in the presence of a hydrosilane or by exchange of fac-(PMe(3))(3)Ru(SiR(3))H(3) with another HSiR(3). The reverse manifold - HH elimination from 4a and trapping with PMe(3) or PMe(3)-d(9) - is also regioselective (1a-d(9)() is predominantly produced with PMe(3)-d(9) trans to Si), but is very unfavorable. At 70 degrees C, a slower but irreversible SiH elimination also occurs and furnishes (PMe(3))(4)RuH(2). The structure of 4a exhibits a tetrahedral P(3)Si environment around the metal with the three hydrides adjacent to silicon and capping the P(2)Si faces. Although strong Si...HRu interactions are not indicated in the structure or by IR, the HSi distances (2.13-2.23(5) A) suggest some degree of nonclassical SiH bonding in the H(3)SiR(3) fragment. Thermolysis of 1a in C(6)D(6) at 45-55 degrees C leads to an intermolecular CD activation of C(6)D(6). Extensive H/D exchange into the hydride, SiMe(3), and PMe(3) ligands is observed, followed by much slower formation of cis-(PMe(3))(4)Ru(D)(Ph-d(5)). In an even slower intramolecular CH activation process, (PMe(3))(3)Ru(eta(2)-CH(2)PMe(2))H (5) is also produced. The structure of intermediates, mechanisms, and aptitudes for PMe(3) dissociation and addition/elimination of H-H, Si-H, C-Si, and C-H bonds in these systems are discussed with a special emphasis on the trans effect and trans influence of silicon and ramifications for SiC coupling catalysis.     

A repertoire of pyridinium-phenyl-methyl cross-talk through a cascade of intramolecular electrostatic interactions

Direct intramolecular cation-pi interaction between phenyl and pyridinium moieties in 1a(+) has been experimentally evidenced through pH-dependent (1)H NMR titration. The basicity of the pyridinyl group (pK(a) 2.9) in 1a can be measured both from the pH-dependent chemical shifts of the pyridinyl protons as well as from the protons of the neighboring phenyl and methyl groups as a result of electrostatic interaction between the phenyl and the pyridinium ion in 1a(+) at the ground state. The net result of this nearest neighbor electrostatic interaction is that the pyridinium moiety in 1a becomes more basic (pK(a) 2.92) compared to that in the standard 2a (pK(a) 2.56) as a consequence of edge-to-face cation (pyridinium)-pi (phenyl) interaction, giving a free energy of stabilization (DeltaDeltaG(o)pKa) of -2.1 kJ mol(-1). The fact that the pH-dependent downfield shifts of the phenyl and methyl protons give the pK(a) of the pyridine moiety of 1a also suggests that the nearest neighbor cation (pyridinium)-pi (phenyl) interaction also steers the CH (methyl)-pi (phenyl) interaction in tandem. This means that the whole pyridine-phenyl-methyl system in 1a(+) is electronically coupled at the ground state, cross-modulating the physicochemical property of the next neighbor by using the electrostatics as the engine, and the origin of this electrostatics is a far away point in the molecule-the pyridinyl-nitrogen. The relative chemical shift changes and the pK(a) differences show that the cation (pyridinium)-pi (phenyl) interaction is indeed more stable (DeltaDeltaG(o)pKa = -2.1 kJ mol(-1)) than that of the CH (methyl)-pi (phenyl) interaction (DeltaDeltaG(o)pKa = -0.8 kJ mol(-1)). Since the pK(a) of the pyridine moiety in 1a is also obtained through the pH-dependent shifts of both phenyl and methyl protons, it suggests that the net electrostatic mediated charge transfer from the phenyl to the pyridinium and its effect on the CH (methyl)-pi (phenyl) interaction corresponds to DeltaG(o)pKa of the pyridinium ion (approximately 17.5 kJ mol(-1)), which means that the aromatic characters of the phenyl and the pyridinium rings in 1a(+) have been cross-modulated owing to the edge-to-face interaction proportional to this DeltaG(o)pKa change.     

Preparation of benzyne complexes of group 10 metals by intramolecular suzuki coupling of ortho-metalated phenylboronic esters: molecular structure of the first benzyne-palladium(0) complex

A series of nickel(II) and palladium(II) aryl complexes substituted in the ortho position of the aromatic ring by a (pinacolato)boronic ester group, [MBr[o-C(6)H(4)B(pin)]L(2)] (M = Ni, L(2) = 2PPh(3) (2a), 2PCy(3) (2b), 2PEt(3) (2c), dcpe (2d), dppe (2e), and dppb (2f); M = Pd, L(2) = 2PPh(3) (3a), 2PCy(3) (3b), and dcpe (3d)), has been prepared. Many of these complexes react readily with KO(t)Bu to form the corresponding benzyne complexes [M(eta(2)-C(6)H(4))L(2)] (M = Ni, L(2) = 2PPh(3) (4a), 2PCy(3) (4b), 2PEt(3) (4c), dcpe (4d); M = Pd, L(2) = 2PCy(3) (5b)). This reaction can be regarded as an intramolecular version of a Suzuki cross-coupling reaction, the driving force for which may be the steric interaction between the boronic ester group and the phosphine ligands present in the precursors 2 and 3. Complex 3d also reacts with KO(t)Bu, but in this case disproportionation of the initially formed eta(2)-C(6)H(4) complex (5d) leads to a 1:1 mixture of a novel dinuclear palladium(I) complex, [(dcpe)Pd(mu(2)-C(6)H(4))Pd(dcpe)] (6), and a 2,2'-biphenyldiyl complex, [Pd(2,2'-C(6)H(4)C(6)H(4))(dcpe)] (7d). Complexes 2a, 3b, 3d, 4b, 5b, 6, and 7d have been structurally characterized by X-ray diffraction; complex 5b is the first example of an isolated benzyne-palladium(0) species.     

Acid-catalysed rearrangements of steroid alkenes-III1. backbone rearrangement of de-a-steroid alkenes and preparation of an aromatic de-a-steroid.

Backbone rearrangement of 10a(methyl)-de-A-cholest-5-ene (3c), 6-ene (3d), 9-ene (3s) and 5(10)-ene (3b) affords products isomeric at C-20 and with the C-10 methyl group in the more stable equatorial position (6a. and 6b). 5-Methylene-10a(methyl)-de-A-cholestane (5) affords similar C-20 isomeric products with both the C-5 and C-10 methyls in the more stable equatorial positions (9a and 9b). The de-A-alkenes (3) provided a convenient starting point for preparation of de-A- cholesta-5,7,9-triene (7). Components (6a, 6b, 7, 9a and 9b) have been used to confirm the widespread occurrence of homologous series of de-A-steroids in marine shales with a mild thermal history.     

Theoretical and experimental reevaluation of the basicity of lambda3-phosphinine

We have investigated the basicity of phosphinine (C5H5P, phosphabenzene) in reevaluating its proton affinity (PA) and gas-phase basicity (GB) and the pK(a) value of its protonated form. As a necessary step, we have first determined its gas-phase proton affinity. Using both mass spectrometric and quantum chemical methods, we have obtained the values PA(C5H5P) = 195.8 +/- 1.0 kcal mol(-1) and GB(298)(C5H5P) = 188.1 +/- 1.0 kcal mol(-1), in good agreement with previous results. We then derived a value of pK(a)(C5H6P+) = -16.1 +/- 1.0 in aqueous solution using three different approaches: the latter markedly differs from the currently available value of -10. The reason for such a discrepancy in the pK(a) of protonated phosphinine in solution is discussed. In the theoretical determination of PAs, evaluation of the basis set superposition error (BSSE) showed that this effect is quite small, being 0.1-0.2 kcal mol(-1) for phosphinine, when a density functional theory (DFT) method in conjunction with a large basis set were used.     

Solubilization of triglycerides in liquid crystals of nonionic surfactant

The solubilization of triglycerides [1,2,3-tributanoylglycerol (TBG) and 1,2,3-trihexanoylglycerol (THG)] in water/octa(oxyethylene) dodecyl ether (C(12)EO(8)) systems has been investigated. Oil-induced changes in the structure of liquid crystals in water/C(12)EO(8) system have been studied by optical observation and small-angle X-ray scattering (SAXS) measurements. In the water/C(12)EO(8)/oil systems, solubilization of THG and TBG induces a transition between H(1) (hexagonal) and L(alpha) (lamellar) liquid crystals at high C(12)EO(8) concentrations, whereas at low surfactant concentrations a H(1)-I(1) (discontinuous micellar cubic phase) transition occurs. This anomalous behavior is attributed to the partitioning of solubilized oil in the micelles. At low surfactant concentrations THG is mainly solubilized into the hydrophobic cores of the surfactant micelles, indicating high swelling or low penetration tendency, resulting in a steep increase in the radius of the aggregates (r(H)), thereby inducing a rod-sphere transition. At high surfactant concentrations, THG is not mainly solubilized into the core but distributed between the palisade layer and the core of the aggregates. The TBG is considerably solubilized into the surfactant palisade layer, indicating a high penetration tendency, resulting in an increase in the effective cross-sectional area per surfactant molecule, a(s). The thermal stability of the I(1) phase increases with the solubilization of THG into the aggregate cores. The percentage deviation of the experimental interlayer spacings (P(d)) from complete swelling was also evaluated for different triglycerides in the H(1) and L(alpha) phases or different surfactant concentrations. It is found that the penetration tendency of triglycerides could be used as a tuning parameter for I(1) phase formation depending on the surfactant concentration and the molecular weight of the oil.     

Extension of the self-consistent spectrophotometric basicity scale in acetonitrile to a full span of 28 pKa units: unification of different basicity scales

The earlier compiled self-consistent spectrophotometric basicity scale in acetonitrile (AN) was expanded to range from 3.8 to 32.0 pK(a) units, that is 28 orders of magnitude. Altogether 54 new relative basicity measurements (DeltapK(a) measurements) were carried out and 37 new compounds were introduced to the scale (it now includes altogether 89 bases). The relative basicity of any two bases in the scale can be obtained by combining at least two independent sets of measurements. Multiple overlapping measurements make the results more reliable. The overall consistency (as defined earlier) of the measurements is s = 0.03 pK(a) units. Thorough analysis of all of our experimental data (DeltapK(a) values of this and earlier works) and experimental pK(a) data in AN available in the literature (works from the groups of Coetzee and Padmanabhan, Kolthoff and Chantooni, Jr., the Schwesinger group, Bren' et al. and some others, altogether 19 papers) was carried out. On the basis of this analysis the anchor point of the scale-pyridine-was shifted upward by 0.20 pK(a) units thereby also revising the absolute pK(a) values of all the bases on the scale. This way very good agreement between our relative data and the absolute pK(a) values of the abovementioned authors was obtained. The revised basicity scale was interconnected with the earlier published self-consistent acidity scale by DeltapK(a) measurements between acids and bases. The rms deviation between the directly measured DeltapK(a) values and the absolute pK(a) values of the compounds was 0.10 pK(a) units.     

Synthesis and Characterization of Sterically Encumbered Derivatives of Aluminum Hydrides and Halides: Assessment of Steric Properties of Bulky Terphenyl Ligands

The synthesis and characterization of several sterically encumbered monoterphenyl derivatives of aluminum halides and aluminum hydrides are described. These compounds are [2,6-Mes(2)C(6)H(3)AlH(3)LiOEt(2)](n)() (1), (Mes = 2,4,6-Me(3)C(6)H(2)-), 2,6-Mes(2)C(6)H(3)AlH(2)OEt(2) (2), [2,6-Mes(2)C(6)H(3)AlH(2)](2) (3), 2,6-Mes(2)C(6)H(3)AlCl(2)OEt(2) (4), [2,6-Mes(2)C(6)H(3)AlCl(3)LiOEt(2)](n)() (5), [2,6-Mes(2)C(6)H(3)AlCl(2)](2) (6), TriphAlBr(2)OEt(2) (7), (Triph = 2,4,6-Ph(3)C(6)H(2)-), [2,6-Trip(2)C(6)H(3)AlH(3)LiOEt(2)](2) (8) (Trip = 2,4,6-i-Pr(3)C(6)H(2)-), 2,6-Trip(2)C(6)H(3)AlH(2)OEt(2) (9), [2,6-Trip(2)C(6)H(3)AlH(2)](2) (10), 2,6-Trip(2)C(6)H(3)AlCl(2)OEt(2) (11), and the partially hydrolyzed derivative [2,6-Trip(2)C(6)H(3)Al(Cl)(0.68)(H)(0.32)(&mgr;-OH)](2).2C(6)H(6) (12). The structures of 2, 3a, 4, 6, 7, 9a, 10a, 10b, 11, and 12 were determined by X-ray crystallography. The structures of 3a, 9a, 10a, and 10b, are related to 3, 9, and 10, respectively, by partial occupation of chloride or hydride by hydroxide. The compounds were also characterized by (1)H, (13)C, (7)Li, and (27)Al NMR and IR spectroscopy. The major conclusions from the experimental data are that a single ortho terphenyl substituent of the kind reported here are not as effective as the ligand Mes (Mes = 2,4,6-t-Bu(3)C(6)H(2)-) in preventing further coordination and/or aggregation involving the aluminum centers. In effect, one terphenyl ligand is not as successful as a Mes substituent in masking the metal through agostic and/or steric effects.     

Decomposition of dinuclear manganese complexes for the preparation of nanostructured oxide materials

The crystal structures of several dinuclear complexes of manganese are reported, and the decomposition and analysis of the nanostructured products derived from them are presented. 1,4,7,10-Tetraazacyclododecane (cyclen) forms dinuclear complexes 1-4 containing doubly oxo-bridged or oxo-acetato bridging ligands depending on the manganese salt used for the reaction. Doubly oxo-bridged 1 crystallizes in the orthorhombic space group Pnma, a = 22.3850(14) A, b = 9.1934(5) A, c = 13.2424(10) A, V = 2725.2(3) A(3). 2, containing [Mn(SCN)5](3-) conteranions, crystallizes in monoclinic space group I2/a with a = 18.2699(10) A, b = 11.2384(6) A, c = 18.6432(9) A, alpha = 90.00 degrees, beta = 114.510(6) degrees, gamma = 90.00 degrees, V = 3483.0(3) A(3). Oxo-acetato-bridged 3 crystallizes in orthorhombic space group Pca21, a = 13.9322(11) A, b = 16.2332(13) A, c = 14.6794(8) A, V = 3320.0(4) A(3). Compound 4 consists of a templated quasi-one-dimensional manganese oxalate crystallized in the triclinic space group P1, a = 9.5442(11) A, b = 10.3758(10) A, c = 21.851(2) A, alpha = 83.720(12) degrees, beta = 80.106(13) degrees, gamma = 85.457(13) degrees, V = 2114.9(4) A(3). Compounds 1, 3, and 4 decompose to nanostructured oxide materials, which may be isolated in bulk as lamellar-structured particles or microspheres or deposited on substrates.     

Acid-base equilibria in gamma-butyrolactone studied by use of pH-ISFETs

pH-ISFETs were used in the study of acid-base equilibria in gamma-butyrolactone (GBL). After the spectrophotometric determination of the pK(a) value of 3,5-dichloropicric acid, the pK(a) values and homo-conjugation constants of various acids (including the conjugate acids of bases) were determined potentiometrically using a Ta(2)O(5)-type pH-ISFET. The values of pK(a) in GBL were in a linear relation with those in propylene carbonate (PC) and 1.0 units smaller on average. The difference in pK(a) between GBL and PC was mainly attributable to the difference in proton solvation. The autoprotolysis constant of GBL, roughly estimated by a rapid titration with a Si(3)N(4)-ISFET, was about 30 on the pK(SH) scale. A comparative study was made of the response speeds of the Ta(2)O(5)- and Si(3)N(4)-type pH-ISFETs and a conventional pH-glass electrode. The result was Si(3)N(4)-ISFET > Ta(2)O(5)-ISFET > glass electrode. Because GBL is not stable against acids and bases, the use of pH-ISFETs was much more convenient than the use of the conventional glass electrode.     

Mechanistic studies of the O2-dependent aliphatic carbon-carbon bond cleavage reaction of a nickel enolate complex

The mononuclear nickel(II) enolate complex [(6-Ph(2)TPA)Ni(PhC(O)C(OH)C(O)Ph]ClO(4) (I) was the first reactive model complex for the enzyme/substrate (ES) adduct in nickel(II)-containing acireductone dioxygenases (ARDs) to be reported. In this contribution, the mechanism of its O(2)-dependent aliphatic carbon-carbon bond cleavage reactivity was further investigated. Stopped-flow kinetic studies revealed that the reaction of I with O(2) is second-order overall and is ～80 times slower at 25 °C than the reaction involving the enolate salt [Me(4)N][PhC(O)C(OH)C(O)Ph]. Computational studies of the reaction of the anion [PhC(O)C(OH)C(O)Ph](-) with O(2) support a hydroperoxide mechanism wherein the first step is a redox process that results in the formation of 1,3-diphenylpropanetrione and HOO(-). Independent experiments indicate that the reaction between 1,3-diphenylpropanetrione and HOO(-) results in oxidative aliphatic carbon-carbon bond cleavage and the formation of benzoic acid, benzoate, and CO:CO(2) (～12:1). Experiments in the presence of a nickel(II) complex gave a similar product distribution, albeit benzil [PhC(O)C(O)Ph] is also formed, and the CO:CO(2) ratio is ～1.5:1. The results for the nickel(II)-containing reaction match those found for the reaction of I with O(2) and provide support for a trione/HOO(-) pathway for aliphatic carbon-carbon bond cleavage. Overall, I is a reasonable structural model for the ES adduct formed in the active site of Ni(II)ARD. However, the presence of phenyl appendages at both C(1) and C(3) in the [PhC(O)C(OH)C(O)Ph](-) anion results in a reaction pathway for O(2)-dependent aliphatic carbon-carbon bond cleavage (via a trione intermediate) that differs from that accessible to C(1)-H acireductone species. This study, as the first detailed investigation of the O(2) reactivity of a nickel(II) enolate complex of relevance to Ni(II)ARD, provides insight toward understanding the chemical factors involved in the O(2) reactivity of metal acireductone species.     

Coordination chemistry of tripyridinedimethane

The ligand tripyridinedimethane (tpdm), consisting of three pyridine residues linked at their ortho carbons by two CH(2) groups, is shown to be a sterically flexible ligand capable of binding in a meridional arrangement in trigonal bipyramidal (tpdm) Cu(II)Cl(2) but binding in a facial arrangement in tetrahedral (tpdm) Cu(I)Cl. Nucleophilic substitution of chloride by (t)BuO(-) and PhC[triple bond]C(-) is possible, and deprotonation of the acidic benzylic protons does not take place because the resulting carbanion cannot achieve coplanarity with the aryl rings. RhCl(3) forms, with tpdm in boiling methanol, a 1:1 kinetic mixture of fac- and mer-isomers RhCl(3)(tpdm). The former isomerizes slowly at RT (room temperature) in DMSO solution into the latter with Rh-N bond dissociation as the rate-determining step.     

Effect of degree,type, and position of unsaturation on the pKa of long-chain fatty acids

Titration of a series of C(18) fatty acids yields pK(a) values that decrease with an increasing degree of unsaturation in the fatty acid chain. The pK(a) values of stearic, elaidic, oleic, linoleic, and linolenic acids were studied and compared to values of area per molecule in a spread monolayer of these acids. The decrease in pK(a) was found to relate to melting point temperature and area per molecule in the spread fatty acid monolayer. The pK(a) value was determined by first dissolving the fatty acid in a high pH solution (pH>10) and subsequently titrating the solution with HCl to obtain the characteristic S-shaped curves used to calculate the pK(a) values. The pK(a) values of stearic, elaidic, oleic, linoleic, and linolenic acids were found to be 10.15, 9.95, 9.85, 9.24, and 8.28, respectively. These pK(a) values were in the same order as area per molecule values of fatty acids in spread monolayers. This suggests that as area per molecule increases the intermolecular distance increases and pK(a) decreases due to reduced cooperation between adjacent carboxyl groups.     

Spectroscopic characterization of hydroxide and aqua complexes of Fe(II)-protoheme, structural models for the axial coordination of the atypical heme of membrane cytochrome b6f complexes

Electronic absorption and resonance Raman (RR) spectra are reported for hydroxide and aqua complexes of iron(II)-protoporphyrin IX (Fe(II)PP) respectively formed in alkaline and neutral aqueous solutions. These compounds with weak axial ligand(s) represent a biomimetic approach of the unusual coordination of the atypical heme c(i) of membrane cytochrome b6f complexes. Absorption spectra and spectrophotometric titrations show that Fe(II)PP in alkaline aqueous cetyltrimethylammonium bromide (CTABr) binds one hydroxide ion, forming a five-coordinated high-spin (HS) complex. In alkaline aqueous ethanol, we confirm the formation of a dihydroxy complex of Fe(II)PP. In the RR spectra of Fe(II)PP dissolved in neutral aqueous CTABr, a mixture of a four-coordinated intermediate spin form with an HS monoaqua complex (Fe(II)PP(H2O)) was observed. The spectroscopic information obtained for Fe(II)PP(OH-), Fe(II)PP(H2O), and Fe(II)PP(OH-)2 was compared with that previously reported for the 2-methylimidazole and 2-methylimidazolate complexes of Fe(II)PP, representative of the most common axial ligation in HS heme proteins. This investigation reveals a very remarkable analogy in the spectral properties of, in one hand, the Fe(II)PP(H2O) and mono-2-methylimidazole complexes and, in the other hand, the Fe(II)PP(OH-) and mono-2-methylimidazolate complexes. The comparisons of the absorption and RR spectra of Fe(II)PP(OH-) and Fe(II)PP(OH-)2 clearly establish that both a redshift of the pi-pi electronic transitions and an upshift of the v8 RR frequency are spectral parameters indicative of porphyrin doming in HS ferrous complexes. Based upon isotopic substitutions (16OH-,16OD-, and 18OH-), stretching modes of the Fe-OH bond(s) of a ferrous porphyrin were assigned for the first time, i.e., at 435 cm(-1) for Fe(II)PP(OH-) (nu(Fe(II)-OH-)) and at 421 cm(-1) for Fe(II)PP(OH-)2 (nu(s)(Fe(II)-(OH-)2). The spectroscopic and redox properties of Fe(II)PP(H2O), Fe(II)PP(OH-), and heme c(i) were discussed and favor a water coordination for the heme c(i) iron.