Cleavage and isomerization of UpU promoted by dinuclear metal ion complexes

The catalysis of phosphoryl transfer by metal ions has been intensively studied in both biological and artificial systems, but the status of the transient pentacoordinate phosphoryl species (as transition state or intermediate) is the subject of considerable debate. We report that dinuclear metal ion complexes that incorporate second sphere hydrogen bond donors not only promote the cleavage of RNA fragments just as efficiently as the activated analogue HPNPP but also provide the first examples of metal ion catalyzed phosphate diester isomerization close to neutral pH. This observation implies that the reaction catalyzed by these complexes involves the formation of a phosphorane intermediate that is sufficiently long-lived to pseudorotate.     

Pseudorotation barriers of biological oxyphosphoranes: a challenge for simulations of ribozyme catalysis

Pseudorotation reactions of biologically relevant oxyphosphoranes were studied by using density functional and continuum solvation methods. A series of 16 pseudorotation reactions involving acyclic and cyclic oxyphosphoranes in neutral and monoanionic (singly deprotonated) forms were studied, in addition to pseudorotation of PF5. The effect of solvent was treated by using three different solvation models for comparison. The barriers to pseudorotation ranged from 1.5 to 8.1 kcal mol(-1) and were influenced systematically by charge state, apicophilicity of ligands, intramolecular hydrogen bonding, cyclic structure and solvation. Barriers to pseudorotation for monoanionic phosphoranes occur with the anionic oxo ligand as the pivotal atom, and are generally lower than for neutral phosphoranes. The OCH3 groups were observed to be more apicophilic than OH groups, and hence pseudorotations that involve axial OCH3/equatorial OH exchange had higher reaction and activation free energy values. Solvent generally lowered barriers relative to the gas-phase reactions. These results, together with isotope 18O exchange experiments, support the assertion that dianionic phosphoranes are not sufficiently long-lived to undergo pseudorotation. Comparison of the density functional results with those from several semiempirical quantum models highlight a challenge for new-generation hybrid quantum mechanical/molecular mechanical potentials for non-enzymatic and enzymatic phosphoryl transfer reactions: the reliable modeling of pseudorotation processes.     

Synthesis and properties of hypervalent electron-rich pentacoordinate nitrogen compounds

Isolation and structural characterization of hypervalent electron-rich pentacoordinate nitrogen species have not been achieved despite continuous attempts for over a century. Herein we report the first synthesis and isolation of air stable hypervalent electron-rich pentacoordinate nitrogen cationic radical (11-N-5) species from oxidation of their corresponding neutral (12-N-5) species. In the cationic radical species, the nitrogen centers adopt a trigonal bipyramidal geometry featuring a 3-center-5-electron hypervalent attractive interaction. The combination of single crystal X-ray diffraction analysis and computational studies revealed weak N–O interactions between the central nitrogen cation and oxygen atoms. This successful design strategy and isolation of air-stable pentacoordinate hypervalent nitrogen species allow further investigations on reactivity and properties resulting from these unusually weakly coordinating interactions in nitrogen compounds.

Structural characterization of hypervalent electron-rich pentacoordinate nitrogen species has long been a synthetic challenge. Here we report the first nitrogen cationic radical (11-N-5) species featuring a weak hypervalent 3c-5e interaction.     

Phosphoryl Transfer Enzymes and Hypervalent Phosphorus Chemistry: A Keynote Lecture of the 7th International Conference on Heteroatom Chemistry

The coordination tendencies of phosphorus to form a hexacoordinated state from a pentacoordinated state which might assist in describing mechanistic action of phosphoryl transfer enzymes are delineated. The factors discussed include substrate and transition or intermediate state anionicity; hydrogen bonding; packing effects, i.e., van der Waals forces; the ease of formation of hexacoordinate phosphorus from lower coordinate states; and the pseudorotation problem common to nonrigid pentacoordinate phosphorus. In view of the work reported in this account and recent work on enzyme promiscuity and moonlighting activities, it is suggested that donor action should play a role in determining active-site interactions in phosphoryl transfer enzyme mechanisms.     

The cause for tremendous acceleration of chloride substitution via base catalysis in the chloro pentaammine cobalt(III) ion

The base hydrolysis reaction of Co(NH(3))(5)Cl(2+) was investigated using density functional theory and molecular orbital methods. Geometries and energies of conjugate bases, intermediates, transition states, and minimum energy crossing points were computed. For the base hydrolysis of Co(NH(3))(5)Cl(2+), three pathways might operate: the mechanism proposed by Basolo and Pearson, the mechanism via a hexacoordinated intermediate exhibiting a triplet ground state, and a fully stereomobile I(d) mechanism. The hexacoordinated intermediate can lose the leaving ligand readily to form a square pyramidal pentacoordinated intermediate with a triplet state, which interconverts rapidly and reversibly into the Basolo-Pearson trigonal bipyramid with a singlet state. Due to its high activation energy, a stereochemical rearrangement via a Berry pseudorotation does not take place. The intermediates are not protonated because their pK(a) values are ~5 for the hexacoordinated intermediate and ~-6 for the trigonal bipyramidal pentacoordinated intermediate. The Basolo-Pearson mechanism proceeds with 50% stereoretention and 50% stereomobility. In the case that the hexacoordinated intermediate converts into the trigonal bipyramid, products with the same stereochemistry would be obtained. If, however, for the square pyramidal intermediate with a triplet state the entering ligand competes efficiently with the rearrangement into the trigonal bipyramid or if the substitution takes place at the hexacoordinated intermediate via, e.g., the I(d) mechanism, the reaction would proceed with retention of the configuration. Direct substitution via the I(d) mechanism, operating for azide and to a small extent also for water, is fully stereomobile. Computations on the Basolo-Pearson mechanism have also been performed for the chloro pentaammine complexes of chromium(III), ruthenium(III), and rhodium(III). This pathway might operate for chromium(III) but not for ruthenium(III) and rhodium(III).     

Berry pseudorotation mechanism for the interpretation of the 19F NMR spectrum in PF5 by ab initio molecular dynamics simulations.

For the first time, theoretical evidence that confirms the importance of the Berry pseudorotation process in the interpretation of the 19F NMR spectrum of phosphorus pentafluoride (PF5) is presented. Ab initio molecular dynamics simulations have been performed to generate a large number of configurations used for NMR parameter computations at the density functional theory level. Two different temperatures were set to highlight the effect of pseudorotation process on the NMR spectrum. Average 19F chemical shifts and spin-spin coupling constants calculated for the five fluorine atoms converge towards the NMR equivalence of the five atoms when the Berry pseudorotation mechanism is accounted for.     

CYCLIC OXYPHOSPHORANES

Abstract

A review on pertinent information on cyclic oxyphosphoranes is presented. Recent X-ray structures and variable temperature ¹H NMR investigations of cyclic pentaoxyphosphoranes reveals a preference for a boat conformation for saturated six-membered rings in apical-equatorial orientations of trigonal bipyramids. These studies include five-, six-, and seven-membered rings and show that the solid state structures are retained in solution. Apical-equatorial ring pseudorotations are more facile for five-membered rings, whereas ligand exchange via diequatorial ring placement is more facile for the larger rings. The importance of the apical-equatorial ring orientation for phosphorinanes appearing as trigonal bipyramidal intermediates in enzymatic reactions of cyclic AMP analogs is emphasized.     

Cyanide-promoted demetalation of TrpyNiNCO: a route to sensitive metallotripyrrins of CoII, FeII, and MnII

Etheral solutions of free base tripyrrins (HTrpy) were prepared by treatment of nickel isocyanate complexes (TrpyNiNCO) with excess cyanide. From these solutions sensitive metallotripyrrins with cobalt(II), iron(II), and manganese(II) ions (TrpyMX) and with a choice of external ligands X could be obtained in pure, crystalline form. Four cobalt and one iron chelate were characterized by X-ray crystallography. Tetracoordinate cobalt(II) species with X = I, NCO, and NCS displayed unstrained tetrahedral coordination geometries, whereas the pentacoordinate TrpyCoNO3 with the O,O-nitrato ligand narrows a trigonal bipyramidal coordination. TrpyFeNCO undergoes a redox-transformation to (TrpyFeNCO)2O upon crystallization and was structurally characterized as this with an almost linear Fe-O-Fe subunit. Donor association was studied by UV-vis spectroscopy employing different solvents and showed that TrpyMnX and TrpyFeX species are very prone to the formation of pentacoordinate species, whereas TrpyCoX compounds have an intermediate tendency to do so. Nevertheless, complex fragments of all three metal ions form 1D coordination polymers with dicyanamido ligands, which were investigated by means of IR and SQUID measurements.     

Catalytic role of metal ion in the selection of competing reaction paths: a first principles molecular dynamics study of the enzymatic reaction in ribozyme

By using finite temperature first principles molecular dynamics, the mechanism of the enzymatic reaction of ribozyme was investigated for both the anionic and the radical charge states of the modeled RNA fragment. In the case of the anionic system, a pseudorotation and the subsequent 3' --> 2' migration occur in a vacuum, rather than the self-cleavage of the phosphodiester. On the other hand, when either a divalent metal ion (Mg(2+)) catalyst or the continuous hydrogen bond network of the solvent is present, the reaction path of the anionic species changes dramatically, going toward the transesterification channel. In a radical system, the transesterification can occur without a metal catalyst, as a consequence of the displacement of a hole (empty electronic state) along the reaction path. Thus, the present analysis suggests that a metal ion might be essential not only in lowering the activation barrier but also in selecting the reaction path among those corresponding to possible different charge states of the intermediate structure in vivo. Furthermore, simulation of the anionic species in solution shows that, in the absence of a metal catalyst, water molecules cooperate with the proton transfer via a proton wire mechanism and the hydrogen bond network plays a crucial role in preventing pseudorotations. On the other hand, when a metal cation is present in the vicinity of the site where the nucleophilic attack occurs, the hydrogen bond network is interrupted and detachment of the proton, enhanced by the catalyst, does not give rise to any proton-transfer process.     

Solution-phase energy profiles for trigonal bipyramidal species postulated as intermediates for the hydrolysis of methyl ethylene phosphate

We present results of solution-phase ab initio and DFT investigations on the trigonal bipyramidal (TBP) intermediates postulated for the hydrolysis of methyl ethylene phosphate (MEP). A key intermediate for the hydrolysis would not be a TBP species with the hydroxyl group axial, but would be a TBP intermediate with the hydroxyl group equatorial. Considering the reaction pathways through this intermediate, not only exclusive ring opening in the dilute alkaline hydrolysis of MEP but also significant amount of exocyclic cleavage in the strong alkali can be rationalized. This interpretation is in accord with the mechanisms proposed by Lim et al. and by Lönnberg et al.     

Organo-nonmetallic chemistry: Pentacoordinate,ten-electron (10-X-5) compounds of silicon,phosphorus and sulfur

Abstract

We have shown that ligands to nonmetals can be designed to stabilize five-coordinate species, relative to four- or six-coordinate ones. Nondissociative permutational isomerization of identically substituted hypervalent 10-Si-5 siliconate anions and neutral 10-P-5 phosphoranes is faster for the isoelectronic isostructural silicon species. Nucleophile mediated stereochemical inversion in silanes which are substituted by ligands which stabilize trigonal bipyramidal species is shown to proceed by pseudorotation of an intermediate 10-Si-5 species.     

不对称环磷化合物的合成及立体化学(Ⅰ)─环磷酰氯和3－羟基异噁唑的反应及其立体化学

研究了2-氧代-2-氯-4-取代苯基-5,5-二甲基-1,3,2-二氧磷杂环己烷与3-羟基异唑的反应,得到的氧磷酰化产物含有顺反两种异构体,用¹HNMR、³¹PNMR、X射线衍射确定了它们的构型,并讨论了亲核取代反应中手性磷原子构型保持和翻转的机理,测定了异构体的生物活性。     

Kinetics and mechanism of the aminolysis of aryl phenyl chlorothiophosphates with anilines

Kinetic studies of the reactions of aryl phenyl chlorothiophosphates (1) and aryl 4-chlorophenyl chlorothiophosphates (2) with substituted anilines in acetonitrile at 55.0 degrees C are reported. The negative values of the cross-interaction constant rhoXY (rhoXY = -0.22 and -0.50 for 1 and 2, respectively) between substituents in the nucleophile (X) and substrate (Y) indicate that the reactions proceed by concerted SN2 mechanism. The primary kinetic isotope effects (kH/kD = 1.11-1.13 and 1.10-1.46 for 1 and 2, respectively) involving deuterated aniline nucleophiles are obtained. Front- and back-side nucleophilic attack on the substrates is proposed mainly on the basis of the primary kinetic isotope effects. A hydrogen-bonded, four-center-type transition state is suggested for a front-side attack, while the trigonal bipyramidal pentacoordinate transition state is suggested for a back-side attack. The MO theoretical calculations of the model reactions of dimethyl chlorothiophosphate (1') and dimethyl chlorophosphate (3') with ammonia are carried out. Considering the specific solvation effect, the front-side nucleophilic attack can occur competitively with the back-side attack in the reaction of 1'.     

Syntheses and structures of hypervalent pentacoordinate carbon and boron compounds bearing an anthracene skeleton--elucidation of hypervalent interaction based on X-ray analysis and DFT calculation

Pentacoordinate and tetracoordinate carbon and boron compounds (27, 38, 50-52, 56-61) bearing an anthracene skeleton with two oxygen or nitrogen atoms at the 1,8-positions were synthesized by the use of four newly synthesized tridentate ligand precursors. Several carbon and boron compounds were characterized by X-ray crystallographic analysis, showing that compounds 27, 56-59 bearing an oxygen-donating anthracene skeleton had a trigonal bipyramidal (TBP) pentacoordinate structure with relatively long apical distances (ca. 2.38-2.46 A). Despite the relatively long apical distances, DFT calculation of carbon species 27 and boron species 56 and experimental accurate X-ray electron density distribution analysis of 56 supported the existence of the apical hypervalent bond even though the nature of the hypervalent interaction between the central carbon (or boron) and the donating oxygen atom was relatively weak and ionic. On the other hand, X-ray analysis of compounds 50-52 bearing a nitrogen-donating anthracene skeleton showed unsymmetrical tetracoordinate carbon or boron atom with coordination by only one of the two nitrogen-donating groups. It is interesting to note that, with an oxygen-donating skeleton, the compound 61 having two chlorine atoms on the central boron atom showed a tetracoordinate structure, although the corresponding compound 60 with two fluorine atoms showed a pentacoordinate structure. The B-O distances (av 2.29 A) in 60 were relatively short in comparison with those (av 2.44 A) in 59 having two methoxy groups on the central boron atom, indicating that the B-O interaction became stronger due to the electron-withdrawing nature of the fluorine atoms.     

Pentacoordinate phosphoranes with reversed apicophilicity as stable intermediates in a mitsunobu-type reaction

Diisopropyl azodicarboxylate (DIAD) undergoes a cycloaddition reaction with the cyclic phosphites CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2)PX (1) [X = NCS (a), N(3) (b), Cl (c), NHMe (d) and Ph (e)] to afford the novel pentacoordinate phosphoranes 2a-e as crystalline solids. This result is different from the reaction of PPh(3) with DIAD used in the well-known Mitsunobu reaction. X-ray crystallography of 2a, 2b, and 2d reveals that the nitrogen, rather than the oxygen, occupies an apical position of the trigonal bipyramidal phosphorus. This is in violation of the commonly accepted preferences for substituents in trigonal bipyramidal phosphorus. In 2e, although the oxygen of the five-membered ring occupies the expected apical position, the phenyl group also occupies (the other) apical position, forcing the more electronegative oxygen atoms of the eight-membered ring to span equatorial-equatorial positions. In contrast to the above, the isocyanato compound CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2)PNCO (1f), upon treatment with DIAD, affords compound 3 to which a tetracoordinate structure is assigned.     

金属、配体和溶剂之间的协同性：基于密度泛函理论研究含双锌离子配合物催化磷酸二酯裂解的反应机理

Density functional theory (DFT)-Tao-Perdew-Staroverov-Scuseria (TPSS) functional calculations on dizinc complex-mediated phosphodiester cleavage indicate a general base catalytic mechanism. 2-hydroxylpropyl-4-nitrophenyl phosphate (HPNP) favors the bridging of two Zn ions by the formation of two coordination bonds between terminal phosphate oxygens and Zn ions. The Zn-bound hydroxide deprotonates the hydroxyl on the side chain of HPNP and consequently the alkoxide is stabilized by coordination to a Zn ion and a hydrogen-bond to Zn-bound water. A water molecule is tightly bound to two amino protons in the bis(1,4,7-triazacyclononane) ligand and this determines the orientation of HPNP during a nucleophilic attack to form a trigonal bipyramidal PO5 intermediate and it also weakens the bond between phosphorus and the phenolate, which makes the leaving of the latter easier. The phenolate formed after the collapse of the five-coordinated phosphorus intermediate easily coordinates to a Zn ion. Surprisingly, the stabilizing solvent effect for the transition state after the formation of the PO5 intermediate is much stronger (at least 42 kJ·mol-1) than that of all other species as they have solvation energies that fluctuate around 12.6 kJ·mol-1. Thus, the overall free energy barrier for this reaction after reactant-binding and before product release is about 17.0 kJ·mol -1, which is too low to be rate-determining. The rate-determining step is very likely part of the release process of the products. Based on various calculations, we discuss possible reasons for the different catalytic efficiencies of the dizinc complex and the enzymes.     

DFT研究Schrock钼催化剂催化的丙烯和丙烯腈复分解反应机理

使用密度泛函理论方法研究了Schrock钼催化剂催化的丙烯和丙烯腈复分解反应机理。研究结果表明：所有金属环丁烷中间体都是三角双锥结构,配体OCF₃和NMe占据三角双锥结构的2个顶点。大部分过渡态具有与金属环丁烷中间体相似的结构特征。Schrock钼催化剂催化的丙烯和丙烯腈的复分解反应包含了3个反应步骤。基于不同通道过渡态结构的相对能量,我们预测顺式和反式产物的产率为9∶1,这个结果与实验事实吻合得很好。     

Syntheses, structures, and thermolyses of pentacoordinate 1,2-oxastibetanes: potential intermediates in the reactions of stibonium ylides with carbonyl compounds

[reaction: see text] Pentacoordinate 1,2-oxastibetanes 14a-d, which are formal [2 + 2]-cycloadducts of the reactions of stibonium ylides with carbonyl compounds, were successfully synthesized by the reactions of the corresponding bromo-2-hydroxyalkylstiboranes with NaH. The crystal structures of 14a and 14c were established by X-ray crystallographic analyses, showing their distorted trigonal bipyramidal structures and smaller C-Sb-O angles of the four-membered ring around antimony than the C-P-O angle of pentacoordinate 1,2-oxaphosphetane 3. The 1H, 13C, and 19F NMR spectra of 14a-d are consistent with the trigonal bipyramidal structure in the solution state. Although 14a did not decompose at all at 220 degrees C in o-xylene-d(10), the thermolyses of 3-phenyl-1,2-oxastibetane 14c were carried out at 220 degrees C in o-xylene-d(10) and at 140 degrees C in acetonitrile-d(3) to give the corresponding oxirane 28 with retention of configuration and cyclic stibinite 25. The formation of 28 is explained by apical-equatorial ligand coupling around antimony via a polar transition state, which is more favorable than olefin formation. In contrast, the thermolyses of 14c in the presence of LiBr and LiBPh4 gave oxirane 29 with inversion of configuration and the olefin 30, respectively. The formation of 29 and 30 is considered to proceed via an anti-betaine-type intermediate and hexacoordinate 1,2-oxastibetanide 36, respectively. Selective formation of 28, 29, and 30 in the thermolyses of 14c, which is regarded as an intermediate in the reaction of an alpha-phenyl-substituted stibonium ylide with a carbonyl compound, showed that the change of the reaction conditions controls the reactivity of a 1,2-oxastibetane compound.     

OXYPHOSPHORANE MODELS FOR NUCLEOPHILIC DISPLACEMENTS AT Pα AND Pγ OF ADENOSINE-5′ TRIPHOSPHATE

Abstract

The reaction of dimethylphosphorous triethylpyrophosphoric anhydride, (CH₃O)₂POP(O)(OC₂H₅)OP(O)(OC₂H₅)₂, with hexafluorobiacetyl, CF₃COCOCF₃, yields 4,5-bis(trifluoromethyl)2,2-dimethoxy-2-triethylpyrophosphato-2,2-dihydro-1,3,2-dioxaphospholene. This oxyphosphorane, with a pyrophosphate group at the apical position of trigonal bipyramidal phosphorus, simulates the pentacovalent intermediate in the addition-elimination mechanism of nucleophilic displacements at the Px and Py centers of adenosine-5′ tri-phosphate. The oxyphosphorane is remarkably stable in solution, although the pyrophosphate group is easily displaced by an alkoxy group in base-catalyzed reactions with alcohols.     

Complexation of tris(pentafluorophenyl)silanes with neutral Lewis bases

A detailed analysis of monodentate and bidentate complexation of tris(pentafluorophenyl)silyl (TPFS) derivatives with neutral Lewis bases was performed. The NMR spectroscopy and X-ray diffraction analysis (11 structures) were the key methods to characterize tetra- or pentacoordinate silicon compounds, whereas the peculiarities of crystal packing were analyzed by means of DFT calculations. The interaction of TPFS-X (X = F, Cl, OTf) with strong Lewis bases (HMPA, N-methylpyrrolidinone) may afford three different species: neutral pentacoordinate TPFS(X)-L, cationic tetracoordinate TPFS-L⁺ X⁻, and cationic pentacoordinate TPFS-(L)⁺₂X⁻, representatives of each type were characterized by X-ray diffraction. A variety of complexes with bidentate complexation, featuring the trigonal bipyramidal geometry with apical C₆F₅-group was prepared and structurally characterized. The extent of Si-C_apical bond elongation depends on the donating ability of the coordinating ligand, with the longest Si-C bond of 1.981(1) Å observed for six-membered complex of TPFS-ether of N-(2-hydroxybenzoyl)pyrrolidine.