Domingo, 2 de Diciembre 2012

Conferencia Dr. Robert Papoular

El Dr. Papoular, ofrecerá la siguiente conferencia durante su estancia en el programa de Maestría en Química:



Lugar: aula Q 102

Hora: 12 m

Abstract:The on-going development of sophisticated high-resolution synchrotron X-ray powder diffraction beamlines, in combination with advancement in analysis software, makes it possible to solve structures for more and more complex pharmaceutical crystalline materials ab-initio. Increased complexity may arise from greater number of degrees of freedom of the molecular moieties or from the reduced symmetry of the crystal. The 11-BM synchrotron powder diffraction beamline at the Argonne Advanced Photon Source, put into operation in 2007, provides the high throughput and the high resolution required to investigate weakly scattering drugs, while minimizing the overlap of Bragg peaks in the measured powder patterns in order to allow for the indexing of low-symmetry unit cells. The subsequent data analysis using the single software package EXPO 2009: (i) indexes the patterns, (ii) ranks suitable crystal symmetries [i.e., space groups] and (iii) solves the structure using simulated annealing for flexible molecular models of linked rigid groups.

The power of 11-BM and EXPO2009 in combination is readily demonstrated on examples pertaining to two important powdered pharmaceuticals: (1) the chemotherapy agent Tegafur C8H9FN2O3 [β-form] and (2) the local anesthetic Tetracaine Hydrochloride (TCHC C15H25O2N2+,Cl-). Monoclinic β-Tegafur was initially solved from single-crystal data by Nakai et al. and reported in 1986 in the Chem. Pharm. Bull. The structure of triclinic TCHC was first published in 2002 by Nowell et al. in the New J. Chem. The synchrotron powder dataset was then indexed with DICVOL (Boultif & Loüer, 1991) and subsequently solved with DASH (David& Shankland, 2001).

A third and final example relates to the propensity for polymorphism of pharmaceutical drugs. A key feature of the 11-BM beamline is its low/high-temperature in-situ capability. In a recent study on the modifications of TCHC, two distinct patterns were obtained at room temperature from the same initial powdered sample. Polymorphism or blunder ? This issue was eventually resolved by slowly varying temperature at 11-BM and watching one pattern gradually transform into the other. Both were indeed successfully indexed by the N-TREOR09 option of the EXPO2009 package.

This work is done in collaboration with Dr. Brian H Toby [ APS / ANL / USA ] and Prof. Viatcheslav N Agafonov [ Faculté de Pharmacie, Université de Tours, France ].

Reference :

A. Altomare, M. Camalli, C. Cuocci, C. Giacovazzo, A. Moliterni and R. Rizzi

“EXPO2009: structure solution by powder data in direct and reciprocal space”

J. Appl. Cryst. (2009) 42, 1197-1202.

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