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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Crystal Engineering of an Anti-HIV Drug Based on the Recognition of Assembling Molecular Frameworks

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Author(s):
Martins, Felipe T. [1] ; Paparidis, Nikolas [1] ; Doriguetto, Antonio C. [2] ; Ellena, Javier [1]
Total Authors: 4
Affiliation:
[1] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13560970 Sao Carlos, SP - Brazil
[2] Univ Fed Alfenas, Dept Ciencias Exatas, BR-37130000 Alfenas, MG - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Crystal Growth & Design; v. 9, n. 12, p. 5283-5292, DEC 2009.
Web of Science Citations: 28
Abstract

A rational strategy was employed for design of an orthorhombic structure of lamivudine with maleic acid. On the basis of the lamivudine saccharinate structure reported in the literature, maleic acid was chosen to synthesize a salt with the anti-HIV drug because of the structural similarities between the salt formers. Maleic acid has an acid-ionization constant of the anti first proton and an arrangement of their hydrogen bonding functionalities similar to those of saccharin. Likewise, there is a saccharin-like conformational rigidity in maleic acid because of the hydrogen-bonded ring formation and the Z-configuration around the C=C double bond. As was conceivably predicted, lamivudine maleate assembles into a structure whose intermolecular architecture is related to that of saccharinate salt of the drug. Therefore, a molecular framework responsible for crystal assembly into a lamivudine saccharinate-like structure could be recognized in the salt formers. Furthermore, structural correlations and structure-solubility relationships were established for lamivudine maleate and saccharinate. Although there is a same molecular framework in maleic acid and saccharin, these salt formers are Structurally different in some aspects. When compared to saccharin, neither out-of-plane SO(2) oxygens nor a benzene group occur in maleic acid. Both features could be related to higher solubility of lamivudine maleate. Here, we also anticipate that multicomponent molecular crystals of lamivudine with other salt formers possessing the molecular framework responsible for crystal assembly can be engineered successfully. (AU)

FAPESP's process: 07/07185-5 - Screening, characterization and evaluation for novel crystal forms from antiretroviral and antineoplastic drugs
Grantee:Felipe Terra Martins
Support Opportunities: Scholarships in Brazil - Doctorate