Computational mutagenesis reveals the role of active-site tyrosine in stabilising a boat conformation for the substrate: QM/MM molecular dynamics studies of wild-type and mutant xylanases.

Molecular dynamics simulations have been performed for non-covalent complexes of phenyl beta-xylobioside with the retaining endo-beta-1,4-xylanase from B. circulans (BCX) and its Tyr69Phe mutant using a hybrid QM/MM methodology. A trajectory initiated for the wild-type enzyme-substrate complex with the proximal xylose ring bound at the -1 subsite (adjacent to the scissile glycosidic bond) in the (4)C(1) chair conformation shows spontaneous transformation to the (2,5)B boat conformation, and potential of mean force calculations indicate that the boat is approximately 30 kJ mol(-1) lower in free energy than the chair. Analogous simulations for the mutant lacking one oxygen atom confirm the key role of Tyr69 in stabilizing the boat in preference to the (4)C(1) chair conformation, with a relative free energy difference of about 20 kJ mol(-1), by donating a hydrogen bond to the endocyclic oxygen of the proximal xylose ring. QM/MM MD simulations for phenyl beta-xyloside in water, with and without a propionate/propionic acid pair to mimic the catalytic glutamate/glutamic acid pair of the enzyme, show the (4)C(1) chair to be stable, although a hydrogen bond between the OH group at C2 of xylose and the propionate moiety seems to provide some stabilization for the (2,5)B conformation.

Dyotropic rearrangement of alpha-lactone to beta-lactone: a computational study of small-ring halolactonisation.

Transition structures have been optimised using the B3LYP/6-31+G* density functional level method, in vacuum and in implicit (PCM) and explicit (DFT/MM) aqueous solvation, for the degenerate rearrangement of the alpha-lactone derived by the formal addition of Cl(+) to acrylate anion and for the dyotropic rearrangement of this to the beta-lactone. Despite being lower in energy than the alpha-lactone, there is no direct pathway to the beta-lactone from the acrylate chloronium zwitterion, which is the transition structure for the degenerate rearrangement. This may be rationalised by consideration of the unfavorable angle of attack by the carboxylate nucleophile on the beta-position; attack on the alpha-position involves a less unfavorable angle. Formation of the beta-lactone may occur by means of a dyotropic rearrangement of the alpha-lactone. This involves a high energy barrier for the acrylate derived alpha-lactone, but dyotropic rearrangement of the beta,beta-dimethyl substituted alpha-lactone to the corresponding beta-lactone involves a much lower barrier, estimated at about 46 kJ mol(-1) in water, and is predicted to be a facile process.

Computational Investigation of Mechanisms for Ring-Opening Polymerization of ε-Caprolactone: Evidence for Bifunctional Catalysis by Alcohols.

Stepwise addition/elimination and concerted mechanisms for the methanolysis of ε-caprolactone, as a model for the initiation and propagation of ring-opening polymerization (ROP), have been investigated computationally using the B3LYP/6-31G* density functional method, with assistance from one or two ancillary methanol molecules. The effects of specific solvation by these extra methanols in cyclic hydrogen-bonded clusters are very significant, with barrier height reductions of about 50 kJ mol(-)(1). However, the effects of bulk solvation as treated by the polarized continuum model are almost negligible. Increasing the ring size lowers the barriers for both the addition and elimination steps of the stepwise mechanism but does not do so for the concerted mechanism; a stepwise mechanism is preferred for methanol-assisted ROP. The essential catalytic role of solvent molecules in this reaction is to avoid the unfavorable accumulation or separation of charges.

The Walden cycle revisited: a computational study of competitive ring closure to alpha- and beta-lactones.

The text-book Walden cycle which interconverts the stereochemical configurations of chlorosuccinic and malic acids involves a beta-lactone intermediate in preference to an alpha-lactone intermediate because the O(nuc) C Cl angle in the transition structure for the former (174 degrees) is more favourable than that for the latter (139 degrees), as determined by PCM(epsilon = 78.4)/B3LYP/6-31+G* calculations; the smaller ring-strain energy of the beta-lactone contributes little to the reactivity difference.

Dihydrogen complexes of rhodium: [RhH2(H2)x (PR3)2]+ (R = Cy, iPr; x = 1, 2).

Addition of H2 (4 atm at 298 K) to [Rh(nbd)(PR3)2][BAr(F)4] [R = Cy, iPr] affords Rh(III) dihydride/dihydrogen complexes. For R = Cy, complex 1a results, which has been shown by low-temperature NMR experiments to be the bis-dihydrogen/bis-hydride complex [Rh(H)2(eta2-H2)2(PCy3)2][BAr(F)4]. An X-ray diffraction study on 1a confirmed the {Rh(PCy3)2} core structure, but due to a poor data set, the hydrogen ligands were not located. DFT calculations at the B3LYP/DZVP level support the formulation as a Rh(III) dihydride/dihydrogen complex with cis hydride ligands. For R = iPr, the equivalent species, [Rh(H)2(eta2-H2)2(P iPr3)2][BAr(F)4] 2a, is formed, along with another complex that was spectroscopically identified as the mono-dihydrogen, bis-hydride solvent complex [Rh(H)2(eta2-H2)(CD2Cl2)(P iPr3)2][BAr(F)4] 2b. The analogous complex with PCy3 ligands, [Rh(H)2(eta2-H2)(CD2Cl2)(PCy3)2][BAr(F)4] 1b, can be observed by reducing the H2 pressure to 2 atm (at 298 K). Under vacuum, the dihydrogen ligands are lost in these complexes to form the spectroscopically characterized species, tentatively identified as the bis hydrides [Rh(H)2(L)2(PR3)2][BAr(F)4] (1c R = Cy; 2c R = iPr; L = CD2Cl2 or agostic interaction). Exposure of 1c or 2c to a H2 atmosphere regenerates the dihydrogen/bis-hydride complexes, while adding acetonitrile affords the bis-hydride MeCN adduct complexes [Rh(H)2(NCMe)2(PR3)2][BAr(F)4]. The dihydrogen complexes lose [HPR3][BAr(F)4] at or just above ambient temperature, suggested to be by heterolytic splitting of coordinated H2, to ultimately afford the dicationic cluster compounds of the type [Rh6(PR3)6(mu-H)12][BAr(F)4]2 in moderate yield.

QM/MM determination of kinetic isotope effects for COMT-catalyzed methyl transfer does not support compression hypothesis.

Secondary alpha-D3 kinetic isotope effects calculated by the hybrid AM1/TIP3P/CHARMM method for the reaction of S-adenosylmethionine with catecholate anion in aqueous solution and catalyzed by rat liver catechol O-methyltransferase at 298 K are 0.94 and 0.85, respectively, in good accord with experiment. The large inverse effect for the enzymatic reaction is not due to compression but arises from significant increases in the stretching and bending force constants involving the isotopically substituted atoms of the transferring methyl group as between the reactant complex and the transition structure, larger than for the reaction in water.

Silver-phosphine complexes of the highly methylated carborane monoanion [closo-1-H-CB11Me11]-.

The synthesis of the silver(I) salt of the highly methylated carborane anion [closo-1-H-CB(11)Me(11)](-) is described, Ag[closo-1-H-CB(11)Me(11)] 1, which in the solid state shows close intermolecular Ag...H(3)C contacts. Addition of various monodentate phosphines to 1 results in the formation of the complexes (R(3)P)Ag[closo-1-H-CB(11)Me(11)] [R = Ph, 2; cyclohexyl (C(6)H(11)), 3; (3,5-Me(2)-C(6)H(3)), 4]. All these complexes show close intermolecular Ag.H(3)C contacts in the solid state that are considerably shorter than the sum of the van der Waals radius of methyl (2.00 A) and the ionic radius of silver(I) (1.29 A). For 2 and 3 there are other close intermolecular Ag...H(3)C contacts in the solid state, arising from proximate carborane anions in the crystal lattice. Addition of methyl groups to the periphery of the phosphine ligand (complex 4) switches off the majority of these interactions, leaving essentially a single cage interacting with the cationic silver-phosphine fragment through three CH(3) groups. In solution (CD(2)Cl(2)) Ag...H(3)C contacts remain, as evidenced by both the downfield chemical shift change and the significant line-broadening observed for the cage methyl signals. These studies also show that the metal fragment is fluxional over the surface of the cage. The Ag...H(3)C interactions in solution may be switched off by addition of a stronger Lewis base than [closo-1-H-CB(11)Me(11)](-). Thus, addition of [NBu(4)][closo-1-H-CB(11)H(5)Br(6)] to 2 affords (Ph(3)P)Ag[closo-1-H-CB(11)H(5)Br(6)], while adding Et(2)O or PPh(3) affords the well-separated ion-pairs [(Ph(3)P)(L)Ag][closo-1-H-CB(11)Me(11)] (L = OEt(2) 5, PPh(3) 6,) both of which have been crystallographically characterized. DFT calculations on 2 (at the B3LYP/DZVP level) show small energy differences between the possible coordination isomers of this compound, with the favored geometry being one in which the [(Ph(3)P)Ag](+) fragment interacts with three of the [BCH(3)] vertices on the lower surface of the cage, similar to the experimentally observed structure of 4.

Computational study of electrophilic addition to acrylate anion:cyclic halonium is the transition structure for degenerate rearrangement of alpha-lactones.

The cyclic chloronium or bromonium carboxylate obtained by addition of Cl+ or Br+ to acrylate anion is shown by PCM/B3LYP/6-31+G* calculations to be not an intermediate but a transition structure for interconversion of equivalent halomethyl oxiranones.