Tuesday, May 16, 2006

Joel: JPCB Update

Analysis of Conformational Polymorphism in Pharmaceutical Solids Using Solid-State NMR and Electronic Structure Calculation
J.R. Smith, W. Xu, and D. Raftery
J.Phys.Chem.B (2006)110, 7766.


A detailed analysis of molecular structure in three polymorphic forms of 5-methyl-2-[(2-nitrophenyl)amino]- 3-thiophenecarbonitrile is made using a combination of multidimensional solid-state NMR (SSNMR) experiments and molecular modeling via electronic structure calculations. These compounds, collectively referred to as ROY because of their red, orange, and yellow colors, share a similar molecular structure with the exception of the dihedral angle between the phenyl and thiophene rings. The ROY materials make it possible to study the influence of nearly a single degree of freedom on the associated NMR spectra. Using the 2D PASS (Antzutkin et al. J. Magn. Reson. A 1995, 115, 7) experiment, spectral editing techniques, and DFT-based calculations of the local fields, an analysis is made of the sensitivity of all carbon and nitrogen sites to changing molecular conformation. Chemical shift and dipolar coupling information obtained from these experiments vary noticeably between forms and are subsequently used to quantitatively determine aspects of molecular structure in these materials, including the coplanar angle between the phenyl and thiophene rings. The influence of motion on the methyl and nitro chemical shifts is also investigated. The accuracy of the information obtained from local field analysis and the model structure calculation demonstrates the capabilities of SSNMR as a quantitative structural method.

Anyone interested in REDOR
Homonuclear and Heteronuclear NMR Studies of a Statherin Fragment Bound to Hydroxyapatite Crystals.
V. Raghunathan, J.M. Gibson, G. Goobes, J.M. Popham, E.A. Louie, P.S. Stayton, G.P. Drobny
J.Phys.Chem.B (2006)110, 9324.

Acidic proteins found in mineralized tissues act as nature's crystal engineers, where they play a key role in promoting or inhibiting the growth of minerals such as hydroxyapatite (HAP), Ca10(PO4)6(OH)2, the main mineral component of bone and teeth. Key to understanding the structural basis of protein-crystal recognition and protein control of hard tissue growth is the nature of interactions between the protein side chains and the crystal surface. In an earlier work we have measured the proximity of the lysine (K6) side chain in an SN-15 peptide fragment of the salivary protein statherin adsorbed to the Phosphorus-rich surface of HAP using solid-state NMR recoupling experiments. 15N{31P} rotational echo double resonance (REDOR) NMR data on the side-chain nitrogen in K6 gave rise to three different models of protein-surface interaction to explain the experimental data acquired. In this work we extend the analysis of the REDOR data by examining the
contribution of interactions between surface phosphorus atoms to the observed 15N REDOR decay. We performed 31P-31P recoupling experiments in HAP and (NH4)2HPO4 (DHP) to explore the nature of dipolar coupled 31P spin networks. These studies indicate that extensive networks of dipolar coupled 31P spins can be represented as stronger effective dipolar couplings, the existence of which must be included in the analysis of REDOR data. We carried out 15N{31P} REDOR in the case of DHP to determine how the size of the dephasing spin network influences the interpretation of the REDOR data. Although use of an extended 31P coupled spin network simulates the REDOR data well, a simplified 31P dephasing system composed of two spins with a larger dipolar coupling also simulates the REDOR data and only perturbs the heteronuclear couplings very slightly. The 31P-31P dipolar couplings between phosphorus nuclei in HAP can be replaced by an effective dipolar interaction of 600 Hz between two 31P spins. We incorporated this coupling and applied the above approach to reanalyze the 15N{31P} REDOR of the lysine side chain approaching the HAP surface and have refined the binding models proposed earlier. We obtain 15N-31P distances between 3.3 and 5 Å from these models that are indicative of the possibility of a lysine-phosphate hydrogen bond.

REDOR again
Short and Medium Range Order in Sodium Aluminophosphate Glasses: New Insights from High-resolution Dipolar Solid-State NMR Spectroscopy.
L. Zhang and H. Eckert
J.Phys.Chem.B (2006)110, 8946.

The structures of sodium aluminophosphate glasses prepared by both sol-gel as well as melt-cooling routes have been extensively characterized by high-resolution solid-state 23Na, 27Al, and 31P single and doubleresonance NMR techniques, including quantitative connectivity studies by 27Al T 31P and 23Na T 31P rotational echo double-resonance (REDOR) methods. Studies along four compositional lines, I: (AlPO4)x-(NaPO3)1-x, II: (Na2O)x-(AlPO4)1-x, III: (NaAlO2)x-(NaPO3)1-x, and IV: (Al2O3)x(NaPO3)1-x, reveal that the network structures of those glasses that are accessible by either preparation method are essentially identical. However, the significantly extended glass-forming ranges available by the sol-gel route facilitate exploration of the structure/composition relationships in more detail, revealing a number of interesting universal features throughout the whole glass system. Both short- and medium-range order appear to be controlled strongly by the O/P ratio of the glasses studied: Up to an O/P ratio of 3.5 (pyrophosphate composition), aluminum is predominantly six-coordinated and fully connected to phosphorus (Al(OP)6 sites). In the region 3.5 e O/P e 4.0, a dramatic structural transformation takes place, leading to the appearance of additional four- and fivecoordinated aluminum species whose second coordination spheres are also entirely dominated by phosphorus. The structure of glasses with an O/P ratio of precisely 4.0 (orthophosphate) is dominated by Al(OP)4 units. As the O/P ratio increases beyond 4.0, the average extent of Al-O-P connectivity is decreased significantly. Here, new types of five- and six-coordinated aluminum units, which are only weakly connected to ph osphorus, are formed, while the network modifier is attracted mainly by the phosphate units.

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