Planejamento e determinação estrutural de modificações cristalinas dos fármacos lamivudina e efavirenz
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2013-08-02
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Universidade Federal de Goiás
Resumo
Lamivudine and Efavirenz are anti-HIV drug largely used as, respectively a
non-nucleoside and a nucleoside reverse transcriptase inhibitor as part of
antiretroviral therapies. During the tests to obtain co-crystals of efavirenz with
lamivudine it was obtained a novel crystalline phase, the polymorph of the
hydrochloride salt of lamivudine. The structural and conformational analysis
of this crystal modification showed that this keeps similarities, in
intramolecular and intermolecular level, respectively with lamivudine
hydrochloride and lamivudine hydrochloride monohydrate. Based on the
intermolecular analysis and packing efficiency is expected that the polymorph
of the hydrochloride salt of lamivudine is more soluble than the anhydrous
phase. There are few reports on efavirenz solid state structures and
behaviors. Crystal engineering strategies have not been well-exploited for
this drug. In this sense, we delineate our synthesis strategy from the
structural comparison and possibility of formation of intermolecular
interactions patterns similar to those observed in the cocrystal of efavirenz
and 4,4’-bipyridine. Two 4,4’-bipyridine-like compounds whose heterocycles
are spaced by either an ethylene and an ethane moiety were cocrystallized
together with efavirenz into solid state forms isostructural with respect to that
of the drug cocrystal with 4,4’-bipyridine. The formation of a three-molecule
entity based mainly on the hydrogen bonding donation from two efavirenz
molecules to both pyridyl nitrogens of each coformer unit was kept in the
three efavirenz cocrystals. The introduction of spacer groups in the coformers
has altered the pattern of weak non-classical hydrogen bonds of the type C—
H· · ·O. This intriduction was also related to the formation of a π-π stacking
interaction between pyridyl rings of the ethane-spaced conformer.
Furthermore, a polymorphic form of efavirenz with only one molecule in the
asymmetric unit is reported for the first time here. This polymorph crystallizes
in the monoclinic system and space group C2, strictly similar to form
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MELO, Ariane Carla Campos de. Planejamento e determinação estrutural de modificações cristalinas dos fármacos lamivudina e efavirenz. 2013. 117 f. Dissertação (Mestrado em Química) - Universidade Federal de Goiás, Goiânia, 2013.