Drug Companies Push Into Central Europe - C&EN Global Enterprise

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SOLVING STRUCTURES WITHOUT CRYSTALS Method provides structural solutions to materials lacking long-range order

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state compound, and modern crystallography methods usually can help solve the material's atomic structure, provided that samples ofthe material are available in the form of bulk crystals, even small ones. But for nanoparticles and other materials that lack longrange order, detenniningstnictures is challenging because crystallography methods aren't applicable.

UNDER CONSTRUCTION A new method builds up structures of crystallographically inaccessible clusters (C60 in this example) through an iterative process that's based on ranking the agreement between experimental and theoretical structure data. Light-colored atoms indicate large error.

termining the atomic structures of aperiodic materials using the type of data measured in X-ray and neutron-diffraction studies ofpowders and other noncrystalline samples. According to the researchers, the method may enable structures to be solved with subangstrom resolution even when crystallographic methods fail. "Knowing the structure of a material is a prerequisite to understanding its properties,,, says Simon J. L. Billinge, a professor ofphysics at Michigan State University, East Lansing. Yet for certain types of solids, such as nanometer-sized chunks of semiconductors, the absence of long-range order rules out the possibility of solving the structure via crystallography. So Billinge, PavolJuhas, Phillip M. Duxbury, and their coworkers in computer science at Michigan

Meanwhile, India's Ranbaxy will pay Advent International $324 million for a 97% stake in Terapia, Romania's largest manufacturer and distributor of generic pharmaceuticals. With annual sales of about $80 million, Terapia markets almost 160 products and operates two finisheddosage manufacturing sites in Romania. Advent, a Boston-based private equity firm, bought a 91% stake in Terapia in August 2003 for $44 million. Ranbaxy says Terapia has the knowhow to prepare generics marketing requests to European Union standards. This capability will promote Ranbaxy's business throughout Europe and the former Soviet Union, the firm adds. The two deals follow an unsolicited $1.6 billion bid by Iceland's Actavis for the Croatian generics maker Pliva (C&EN, March 27, page 9). Pliva had sales last year of $1.2 billion.-MICHAEL MCCOY AND JEAN-FRANÇOIS TREMBLAY

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Drug Companies Push Into Central Europe

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2006,440,655). Billinge explains that the procedure was inspired by the rules of promotion and relegation (downgrading) that are used to rank teams in European soccer leagues, such as La Liga in Spain. Named accordingly, the Liga method was used to deduce the structure of C 60 , using PDF data obtained from neutron-scattering measurements on a solid-phase sample of buckeyballs. The team reports that the calculated data set matches the experimentally measured results quite closely, yet the computed structure deviates slightly from the ideal structure of C 60 due to noise in the data and experimental limitations. In a commentary in the same issue of Nature, John J. Rehr, a physics professor at the University of Washington, remarks that "aperiodic materials are among the technologically most interesting nanoscale materials currently under study. The new approach to solving these materials' structures could be widely applicable."—MITCH

A new computational method, though, is poised to help with the problem. Researchers have developed a numerical procedureforde-

anof i-Aventis and Ranbaxy Laboratories are the latest pharmaceutical companies to make acquisitions in the fast-growing Central European generic drugs business. Paris-based Sanofi has spent about $516 million to acquire a 24.9% interest in the Czech generics company Zentiva. Sanofi bought most of the stake from Warburg Pincus, which invested in one of Zentiva's predecessor firms in 1998, and the rest from current and former Zentiva employees. Sanofi, which is now Zentiva's largest shareholder, calls the purchase "a strategic move in the development of Sanof i-Aventis in Central and Eastern Europe." Zentiva was formed in August 2003 by the merger of Léciva and Slovakofarma, the largest drug companies in the Czech Republic and Slovakia, respectively. Zentiva had sales last year of close to $500 million, up 11% over 2004.

State developed a computational technique for building up cluster structures one atom at a time using readily available high-resolution diffraction data. The data, which are known as atomic pair distribution functions (PDFs), consist oflists of interatomic spacings and a histogram that indicates howmany atom pairs share a particular spacing. To build up structures, the algorithm "positions" a small number of atoms in a cluster and then compares the distance list derived from the computer-generated cluster with an experimentally measured list. Distance values obtained from other computer-generated clusters of the same size are also compared with the experimental data. The theoretical cluster that matches the experimental data most closely "wins" that round and is promoted to the next level, where structures of clusters with one additional atom are once again ranked according to the closeness of the match with experimental data {Nature

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