The Role of Lattice Matching Techniques in the Characterization of Polymorphic Forms
An inspection of the recent literature reveals that polymorphism is a frequently encountered phenomenon. The recognition of polymorphic forms plays a vital role in the materials sciences because such structures are characterized by different crystal packing and accordingly have different physical properties. In the pharmaceutical industry, recognition of polymorphic forms can be critical for, in certain cases, a polymorphic form of a drug may be an ineffective therapeutic agent due to its unfavorable physical properties. A check of the recent literature has revealed that in some cases new polymorphic forms are not recognized. In other instances, a supposedly new polymeric form is actually the result of an incorrect structure determination. Fortunately, lattice-matching techniques, which have proved invaluable in the identification and characterization of crystal structures, represent a powerful tool for analyzing polymorphic forms. These lattice-matching methods are based on either of two strategies: (a) the reduced cell strategy–the matching of reduced cells of the respective lattices or (b) the matrix strategy–the determination of a matrix or matrices relating the two lattices coupled with an analysis of the matrix elements. Herein, these techniques are applied to three typical cases–(a) the identification of a new polymorphic form, (b) the demonstration that a substance may not be a new polymorphic form due to missed symmetry, and (c) the evaluation of pseudo polymorphism because of a missed lattice. To identify new polymorphic forms and to prevent errors, it is recommended that these lattice matching techniques become an integral part of the editorial review process of crystallography journals.
Further errors in polymorph identification: furosemide and finasteride.
Reassessment of the reported single-crystal X-ray diffraction characterization of polymorphs of furosemide and finasteride shows that, in each case, incomplete data collections have resulted in the mistaken identification of two forms that are, in fact, identical.
BIOSYNTHESIS OF DAUNORUBICIN GLYCOSIDES: ANALYSIS WITH BLOCKED MUTANTS
ABSTRACT Daunorubicin (daunomycin; NSC 82151) is an anthracycline antibiotic that is useful in the treatment of human leukemias. Several Streptomyces species accumulate higher glycosides of daunorubicin, which can be converted to daunorubicin by simple hydrolysis. We isolated a number of mutants of a daunorubicin glycoside-producing streptomycete, and found that some were deficient in accumulation of daunorubicin glycosides. One such mutant accumulated no detectable anthracyclines, while other mutants accumulated anthracyclines or aglycones that have not been reported before or have been described as co-metabolites of daunorubicin glycosides. Some of these anthracyclines and aglycones were purified and used as substrates in bioconversion experiments with various mutants. The results allowed us to construct a proposed pathway for the biosynthesis of daunorubicin glycosides by this streptomycete. KEYWORDS Anthracycline; daunorubicin; biosynthesis; blocked mutants; biotransformation.