Trigonal Bipyramidal Phosphorane Research Articles

Biologically Relevant Phosphoranes: Hypervalent Phosphorus as Applied to Phosphoryl Transfer Enzymes

The coordination tendencies of phosphorus to form a hexacoordinated state from a pentacoordinated state, which might assist in describing the mechanistic action of phosphoryl transfer enzymes, are delineated. In view of the work reported here 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. Biochemists studying phosphoryl transfer enzymes outline mechanisms of nucleophilic attack at phosphorus that take place by way of proposed trigonal bipyramidal intermediates or transition states. However, recent work has shown the ready availability of higher coordinate forms of phosphorus, particularly the ease of formation of hexacoordinate phosphorus. Our recent work established the X-ray structure of several biorelevant phosphoranes. Included are the structures of a xylofuranose based phosphorane 1 and a thymidine based phosphorane. Dynamic equilibrium between two isomeric forms exists in solution for 1. In addition, bicyclic phosphorane 3 exists in equilibrium between pentacoordinated and hexacoordinated isomeric forms. The rapid exchange process between these two geometries reorients the nucleotidyl or carbohydrate component of the trigonal bipyramidal phosphorane. At an active site, this type of pseudorotational behavior provides a mechanism that could bring another active site residue into play and account for a means for phosphoryl transfer enzymes to express promiscuous behavior. Pseudorotation, a well-founded process in non-enzymatic phosphorus chemistry may have an application in the future of phosphoryl transfer enzyme chemistry.

Quantum mechanical studies on the existence of a trigonal bipyramidal phosphorane intermediate in enzymatic phosphate ester hydrolysis

Phosphate ester hydrolysis is a key step in several enzymatic processes, which follow either a dissociative or an associative mechanism. While in the aqueous phase both pathways are favoured to about the same extent, the associative mechanism is relatively rarely observed. In this paper we report on quantum mechanical calculations for three enzymes HIV integrase, β-phosphoglucomutase and dUTPase, and try to find an explanation for the preference of the associative mechanism in a given enzyme. It is reasonable to suppose that the stabilisation of the pentacovalent, trigonal bipyramidal phosphorane moiety by formation of a covalent bond, one or more hydrogen bonds, or by co-ordination of a divalent metal cation with the equatorial oxygen atoms is the key factor. In all three enzymes studied one of the equatorial oxygen atoms is co-ordinated to a magnesium dication, while a second one is involved in a covalent bond. While in HIV integrase the third oxygen atom may only form a weak hydrogen bond with a solvent water molecule, in β-phosphoglucomutase this atom is stabilised by two strong hydrogen bonds with adjacent protein side chains and in dUTPase it is involved in a covalent bond.

Biologically Relevant Phosphoranes: Synthesis and Structural Characterization of Glucofuranose-Derived Phosphoranes with Penta- and Hexacoordination at Phosphorus

Carbohydrate-based phosphoranes were synthesized by reacting the appropriate diphenol with phosphorus trichloride followed by the addition of chloralose to form 1 and by the addition of isopropylidene-D-glucofuranose to form 2 and 3. Phosphorane 4 was obtained by reacting 1,2-O-isopropylidene-alpha-D-glucofuranosyl-3,5,6-phosphite (13) with a diphenol. For the synthesis of 5-9, the appropriate phosphite was reacted with isopropylidene-glucofuranose. X-ray analyses of 1-9 were carried out successfully. Hexacoordinated structures resulted via oxygen donor action at phosphorus in the cases of phosphoranes 1-3 and via sulfur donor action for phosphoranes 4-6. Trigonal bipyramidal structures formed for 7-9 with the carbohydrate components occupying axial-equatorial sites. The eight-membered ring of the diphenol moiety with weak or no donor groups in 7-9 occupied diequatorial sites of the trigonal bipyramid. Solution NMR data are in agreement with the assigned solid-state structures. Isomerism between penta- and hexacoordination is present in solution for 7. The isomerism observed for 7 and our previous study showing a rapid exchange process that reorients the carbohydrate component of the trigonal bipyramidal phosphorane suggest that these biophosphoranes may serve as models for active sites of phosphoryl-transfer enzymes. At an active site, this type of pseudorotational behavior provides a mechanism that could bring another active site residue into play and account for a means by which some phosphoryl-transfer enzymes express promiscuous behavior.

Biologically Relevant Phosphoranes: Structural Characterization of Glucofuranose- and Xylofuranose-Based Phosphoranes1

Carbohydrate-based phosphoranes were synthesized by reacting 2,2'-ethylidenebis(4,6-di-tert-butylphenyl)fluorophosphite with 1,2-O-isopropylidene-alpha-D-glucofuranose, beta-chloralose, and 1,2-isopropylidene-alpha-D-xylofuranose to form the monocyclic biophosphoranes 1-3, respectively, in the presence of N-chlorodiisopropylamine. Synthesis of the monocyclic biophosphorane 4 was achieved by reacting tris(2,6-di-isopropylphenyl)phosphite with 1,2-O-isopropylidene-alpha-D-glucofuranose in the presence of N-chlorodiisopropylamine. X-ray analysis of 1-4 revealed trigonal bipyramidal structures with the carbohydrate components occupying axial-equatorial sites. An eight-membered ring in 1-3 occupied diequatorial sites of the trigonal bipyramid. Solution and solid state 31P and solution 19F, 1H, and 13C NMR measurements including variable temperature and correlation spectroscopy studies established retention of the solid state structure in solution. A dynamic equilibrium exists among two isomeric forms. These biophosphoranes serve as models for active sites of phosphoryl transfer enzymes. The rapid exchange process reorients the carbohydrate component of the trigonal bipyramidal phosphorane. At an active site, this type of pseudorotational behavior provides a mechanism that could bring another active site residue into play and account for a means by which some phosphoryl transfer enzymes express promiscuous behavior.

P(V) trigonal bipyramidal phosphoranes as model compounds for the description of cAMP‐catalyzed reactions

Abstract13C NMR low‐temperature investigations have revealed that the dioxaphosphorinane ring, trans‐annelated with a cyclopentane ring (3), prefers an equatorial‐apical alignment in trigonal bipyramidal phosphoranes. However, the 13C NMR low‐temperature investigations of the model compound, in which the dioxaphosphorinane ring is trans‐annelated with a tetrahydrofuran ring (4), have shown that the ligand exchange (pseudorotation) in this compound is very fast on the NMR time scale, even at low temperatures. These results are in fairly good agreement with quantum‐chemical calculations.

Crystal and molecular structure of trans-3,4-dihydro-2,3,4-triphenyl-5-phenylmethyl-2H-1,2,3-diazaphosphole 3-oxide

The crystal and molecular structure of the first reported example of a new five-membered cyclic diazaphospholene oxide was solved by X-ray crystallographic techniques. This compound crystallizes in space group P with unit-cell dimensions a= 5.815(2), b= 9.688(4), c= 20.207(9)A, α= 95.47(6), β= 95.04(4), γ= 89.32(4)°, with Z= 2. The five-membered ring is an irregular and almost planar pentagon. The geometry about the phosphorus atom is that of a distorted tetrahedron with angles ranging from 91 to 118°. The formation of a trigonal bipyramidal phosphorane intermediate by addition of nucleophiles at the face opposite to the P–N bond involves relatively small additional bond-angle deformations: this factor may explain the reactivity of this new heterocyclic system toward nucleophiles.

The chemistry of some quaternary derivatives of the 10,11-dihydrodibenzo[b,f]phosphepin system. The kinetics of alkaline hydrolysis, and products of betaine collapse, and a comparison with other phosphonium salts

Alkaline hydrolysis of 10,11-dihydro-5-methyl-5-phenyldibenzo[b,f]phosphepinium iodide (1; R = Ph) proceeds with cleavage of the exocyclic phenyl group at a rate fifty times faster than that observed for the ring-opening, hydrolysis of the 5,5-dimethyl analogue (1; R = Me). Comparison of the rate data and activation energies for hydrolysis of these seven-membered ring salts with those for the acyclic salts [PMePh3][I] and [PMe2Ph2][I] indicates the existence of a ‘seven-membered-ring effect’, which may be due to the preferential occupation by the ring of diequatorial positions in intermediate trigonal-bipyramidal phosphoranes. Hydrolysis of these seven-membered-ring salts proceeds much more slowly than those of related five-membered-ring salts, indicating that relief of ring strain on phosphorane formation is of little importance for the seven-membered-ring compounds. The betaine (9) derived from 10,11-dihydro-5-phenyldibenzo[b,f]phosphepin and styrene oxide collapses in refluxing ethanol to form styrene and the related cyclic phosphine oxide (5; R = Ph); no rearrangement products are formed, in contrast to the reactions of the corresponding betaine derived from triphenylphosphine.

Strain factors in quinquecovalent phosphoranes. Sulphur-containing rings and six-membered rings

Variable-temperature n.m.r. spectroscopy on a range of spirophosphoranes has given data on the increase in energy when five-membered rings containing sulphur attached to phosphorus move from a diequatorial to an apicalequatorial position in a trigonal-bipyramidal phosphorane. The results have been compared with those from the corresponding oxygen-containing systems and the remarkable similarity has been explained in terms of compensating lone-pair orientation and strain terms. Lone-pair orientation effects are also important in determining the preference of six-membered rings containing heteroatoms attached to phosphorus for an apical-equatorial as oppose to a diequatorial disposition in trigonal bipyramidal phosphoranes.

Apicophilicity of the ethylthio-group in trigonal bipyramidal phosphoranes

The variable-temperature n.m.r. spectra of a number of five-co-ordinate spirophosphoranes having P-ethoxy- and P-ethylthio-groups have given data on the energetics of the pseudorotation processes available to the systems. It is concluded that the apicophilicities of ethoxy- and ethylthio-groups are similar. The spirophosphoranes were obtained from 2-substituted 1,3,2-dioxaphospholans by addition to biacetyl, 3-benzylidenepentane-2,4-dione, or 2-phenylacrylophenone, or by condensation with 1,2-diols in the presence of N-chlorodi-isopropylamine.

Relative apicophilicities of alkyl and aryl groups in quinquecovalent phosphoranes

Variable temperature n.m.r. data on the perfluorobiacetyl adducts of phenyl dialkyl- and alkylaryl-phosphinites and on 6-substituted 1,5,7,11-tetraoxa-6-phosphaspiro[5.5]undecanes show that the greater compression at the apical, as opposed to the equatorial, positions in trigonal bipyramidal phosphoranes plays a large part in determining the relative apicophilicities of alkyl and aryl groups in these systems, and that the apicophilicities of methyl and phenyl groups are more similar than previous data had indicated.

ChemInform Abstract: PRODUCT CONTROL IN NUCLEOPHILIC SUBSTITUTION AT TETRAHEDRAL PHOSPHORUS BY THE RELATIVE APICOPHILICITY OF THE NUCLEOPHILE

AbstractBeim Erhitzen von (I) mit NaOH erhält man das Substitutionsprodukt (II), das in das sekundäre Phosphinoxid (III) übergeführt wird.

Product control in nucleophilic substitution at tetrahedral phosphorus by the relative apicophilicity of the nucleophile

A chemical probe for the study of the relative apicophilicity of groups in a trigonal bipyramidal phosphorane is suggested.

The apicophilicity of thio-substituents in trigonal bipyramidal phosphoranes

The variable temperature n.m.r. spectra of a number of five-co-ordinate spirophosphoranes having P-phenoxy- and P-phenylthio-groups have given data on the energetics of the pseudorotation processes available to these systems. It is concluded that the apicophilicities of phenoxy- and phenylthio-groups are similar, with the balance varying according to the nature of the other ligands. Further evidence is given for the high apicophilicity of the hydrogen atom. The concept of multiple turnstile rotation processes is discussed with particular reference to spirophosphoranes.