G. Grossmann

Solid‐state NMR of bisphosphonates adsorbed on hydroxyapatite

Solid‐state 31P and 13C magic angle spinning (MAS) NMR spectra were used to characterize pure bisphosphonates and also bisphosphonates adsorbed on hydroxyapatite. Four geminal bisphosphonates, including the clinically used compounds ethane‐1‐hydroxy‐1,1‐diphosphonic acid, 3‐amino‐1‐hydroxypropane‐1,1‐diphosphonic acid and 4‐amino‐1‐hydroxybutane‐1,1‐diphosphonic acid, five α,ω‐bisphosphonates and phosphonoacetic acid were investigated. NMR spectra of pure and adsorbed bisphosphonates differ in the observed linewidths and in the isotropic chemical shifts. The broad lines reflect mainly the poor crystallinity of the adsorbed compounds. Shifts of δiso in both directions do not reveal a correlation with the molecular structures. The molar ratio of phosphonates adsorbed on hydroxyapatite determined by 31P spectra without cross‐polarization (CP) is approximately two times larger for geminal bisphosphonates than for α,ω‐bisphosphonates and phosphonoacetic acid. 13C CP/MAS spectra of pure and adsorbed bisphosphonates recorded in two cases for identification of adsorbed compounds give additional information about the state of adsorbed compounds. Disodium α,ω‐dihydroxypolymethylene‐α,ω‐bisphosphonates in the solid state show characteristic 13C chemical shifts which are indicative of either odd or even numbers of CH2 groups. Copyright

DIE STRUKTUR VON ALKYL- UND ARYLPERTHIOPHOSPHONSÄUREANHYDRIDEN IN LOSUNG

Abstract The analysis of 1H-, 31P- and 13C-NMR spectra of different alkyl- and arylperthiophosphonic acid anhydrides shows that these compounds prefer a dimeric structure in solution. They exist as 2,4-diorganyl-2,4-dithioxo-1,3,2λ5,4λs-dithiadiphosphetanes. Most of the perthiophosphonic acid anhydrides form configuration isomers which differ in the position of the thioxo groups relatively to the ring plane. The concentration of the trans-isomer is generally larger than that of the cis-isomer. The ratio of the concentration of both isomers is obviously determined by the polarity of the solvent used. Mixing of solutions of different perthiophosphonic acid anhydrides results in unsymmetrical compounds also existing in cis- and trans-configuration. 31P chemical shifts and geminal P-P coupling constants for symmetrical and unsymmetrical perthiophosphonic acid anhydrides are presented and discussed.

Anisotropy of chemical shift and J coupling for P-31 and Se-77 in trimethyl and triphenyl phosphine selenides

The 31P and 77Se magic angle spinning (MAS) nuclear magnetic resonance (NMR) experiments for selenium-77 enriched (70%) trimethylphosphine selenide 1 and triphenylphosphine selenide 2 were carried out in order to determine the nuclear magnetic shielding tensors of both nuclei and to establish values of the phosphorus-selenium indirect spin-spin coupling anisotropy delta J. The m = +1/2 and m = -1/2 subspectra were analysed by the dipolar-splitting-ratio method of Eichele and Wasylischen. For the C(S) molecule 1, delta J was obtained to be +640 +/- 260 Hz from the 31P spectrum and +550 +/- 140 Hz from the 77Se spectrum. Density functional theory (DFT) calculations give a delta J value of about +705 Hz. The value of delta J could not be determined unambiguously by analysis of the 31P spectra for the C1 molecules 2; nevertheless, an estimation of delta J was possible. The principal axis 3 of the phosphorus shielding tensor was determined to be nearly parallel to the PSe bond in 1 and 2. For the selenium shielding of 1, the same orientation was found, whereas in 2, the principal axis 2 of the selenium shielding was found to be oriented nearly along the PSe bond. The experimentally determined phosphorus nuclear magnetic shielding tensors agree well with those calculated by the IGLO method. For those two principal values of the selenium-shielding tensors corresponding to directions nearly perpendicular to the SeP bond, the agreement between calculated and experimental values is satisfactory. For the third one, corresponding to the principal axis close to the SeP bond, the calculated deshielding contributions are distinctly too small for both compounds investigated. Trends observed for the calculated molecular orbital (MO) contributions to the shielding as well as possible reasons for the underestimation of the deshielding contributions along the SeP bond are discussed.

NMR-SPEKTROSKOPISCHE UNTERSUCHUNGEN AN 15N-MARKIERTEN OCTASUBSTITUIERTEN CYCLOTETRAPHOSPHAZENEN

Abstract Aus den 31P- und 15N-NMR-Spektren von 15N-markierten octasubstituierten Cyclotetraphosphazenen, (15NPR2)4; R = F, Cl, Br, OMe, OPh, SEt, NMe2, NHEt bzw. Me, wurden auser den chemischen Verschiebungen δP und δN auch die Kopplungskonstanten 1JPN und 2JPP erhalten. Eine einfache Auswertung der Spektren zur Gewinnung dieser Kopplungskonstanten wird vorgestellt. Die experimentellen NMR-Parameter hangen in erster Linie von der Art des direkt an den Phosphor gebundenen Substituentenatoms ab. Die Kopplungskonstanten 1JPN und 2JPP korrelieren mit der Elektronegativitat der Substituenten und den Bindungszustanden im Phosphazenring. From 31P and 15N n.m.r. spectra of completely labeled octasubstituted cyclotetraphosphazenes (15NPR2)4 (R = F, Cl, Br, OMe, OPh, SEt, NMe2. NHEt, or Me) chemical shifts, δP and δN, as well as coupling constants, 1JPN and 2JPP, were obtained. A simple method of obtaining these coupling constants is presented. The experimental n.m.r. parameters depend, especially, on the nature of...

Calcium−Phosphonate Interactions: Solution Behavior and Ca2+ Binding by 2-Hydroxyethylimino-bis(methylenephosphonate) Studied by Multinuclear NMR Spectroscopy

The tetra-acid 2-hydroxyethylimino-bis(methylenephosphonic acid) (HEIBPH, 1) and its ring condensation product, the triacid 2-hydroxy-2-oxo-4-phosphonemethyl-1,4,2-oxazaphosphorinane (2), were investigated for determination of protonation constants using (31)P, (1)H, and (13)C NMR spectroscopy in a wide pH range. As for other alpha-amino-phosphonic acids, the first protonation of 1 is straightforward and occurs at the nitrogen, while for 2 the first protonation occurs simultaneously at the exo phosphonate group, allowing estimation of the microscopic protonation constants. The complexation of Ca(2+) with 1 in a 1:1 molar ratio in aqueous solutions and in the presence of a 5-fold excess Na(+) is rationalized by the products LCaH(2), LCaH, LCaNaH, LCa, and LCa(2) (L = 1). Only the phosphonate groups are involved in Ca(2+) binding at pH > 3, while the phosphonate, hydroxyl, and amine functionalities coordinate to Ca(2+) at pH > 6-7, as soon as the proton at N is lost. Probable conformation states of ions of 1 and 2 are estimated by means of the dependence of vicinal coupling constants (3)J(HH) and (3)J(PC) from dihedral angles.

Crystal structure, nuclear magnetic resonance spectroscopy and individual gauge for localised orbitals (IGLO) calculations of C6H4P2S6, a new tetrathiadiphosphorinane, and comparison with related P–S compounds

The reaction of 1,2-diphosphinobenzene with sulfur yielded a new constitution of a tetrathiadiphosphorinane ring: 4,6-(1,2-phenylene)-4,6-dithioxo-1,2,3,5,4λ5,6λ5-tetrathiadiphosphorinane the crystal structure of which has been determined, orthorhombic, space group Pbca(no. 61), a= 12.846(4), b= 16.929(7), c= 11.178(6)A and Z= 8. The tetrathiadiphosphorinane ring has a chair structure with axial positions of the 1,2-phenylene carbons and equatorial positions of the terminal sulfur atoms. One molecule per unique volume is an independent structural unit. This is consistent with the fact that the solid-state 31P cross-polarisation magic angle spinning (CP MAS) NMR spectra give two sets of slightly different principal values of the nuclear magnetic shielding tensor. A comparison with the crystal structure and the solid-state NMR data of trans-2,4-diphenyl-2,4-dithioxo-1,3,2λ5,4λ5-dithiadiphosphetane and cis-2,4-(1,8-naphthalenediyl)-2,4-dithioxo-1,3,2λ5,4λ5-dithiadiphosphetane shows that the nuclear shielding does not only depend on the molecular structure. Short intermolecular S ⋯ S distances lead to deshielding effects on the 31P nucleus. Results of individual gauge for localised orbitals (IGLO) calculations of the 31P nuclear shielding of isolated molecules agree, nevertheless, satisfactorily with the experimental principal values and additionally allow the determination of the orientation of the principal axes in the molecular framework. The IGLO calculations indicate that the principal 3 axis for the most shielded principal value lies nearly parallel with the PS bond.

SOLID-STATE NMR STUDIES AND CRYSTAL STRUCTURE OF THE LAWESSON-REAGENT

Abstract X-ray diffraction of the toluene solvate of the Lawesson reagent, C14H14O2P2S4.C7H3, gives the following crystal data: triclinic, PT (no. 2). a = 6.831 (2), b = 9.393 (3), c = 9.793 (3) A, α = 70.33 (2), β = 83.28 (2). γ = 71.35 (2)°, V = 560.6 A3, Z = 1, and D2 = 1.471 Mg m−3. The bond lengths and angles are very close to those observed in the solvent-free crystals. The toluene molecule is disordered over two positions related by an inversion center. The asymmetric unit consists of half the formula unit. This is consistent with the fact that the solid-state 31P CP MAS NMR spectrum gives one set of principal values of the nuclear magnetic shielding tensor. Similar values were obtained for solvates of other aromatic compounds such as benzene, o-dichlorobenzene, methoxybenzene and p-dimethoxybenzene. A comparison with the data for the solvent-free Lawesson reagent shows that the nuclear shielding depends not only on the molecular structure but can also be influenced by short intermolecular S==S dis...

Trans-cyclohexane-1,2-diphosphonates synthesis, structural and NMR spectroscopic investigations.

Abstract A stereospecific addition of sodium diethylphosphite to cyclohexene-1-phosphonic acid diethyl ester 1 was used to synthesize trans-cyclohexane-1,2-diphosphonic acid tetraethyl ester 2b. Acidolysis of the ester yields the corresponding diphosphonic acid 2a. Dissociation constants pK1-pK4 of 2a were obtained in aqueous solutions by precision potentiometric titration. The molecular structure of solid 2a determined by X-ray diffraction shows a slightly disturbed chair form of the cyclohexane ring and a bisaxial conformation of the phosphonate groups with a P–C–C–P dihedral angle of 143°. Results of molecular modeling of 2a as well as of its anions (with and without consideration of Na+ cations) obtained by semi-empirical MNDO methods and by empirical force field calculations including molecular dynamics are reported. The investigation of organic solutions of 2b and of aqueous solutions of 2a by NMR spectroscopy allows conclusions concerning the conformative state via a Karplus-type relation for the v...

Dithiadiphosphetanes. NMR Studies in Solution and Solid State

Abstract Solid state NMR spectra and solution spectra of dithiadiphosphetanes [RP(S)S]2 are compared and discussed with respect to configuration and conformation of these compounds.

Quantum Chemical Calculations of P-N and P-P Coupling Constants of Cyclotriphosphazenes

Abstract Semiempirical quantum chemical calculations using the SOX approximation have been carried out in order to facilitate the interpretation of the P-N and P-P couplinq constants of a series of 15N labelled hexasubstituted cyclotriphosphazenes (15NPX2)3. A change of sign within the series was confirmed