2 research outputs found
Base-Paired and Base-Stacked Structures of the Anti-HIV Drug Lamivudine: A Nucleoside DNA-Mimicry with Unprecedented Topology
We have prepared a DNA-mimicry of nucleosides in which
the anti-HIV
drug lamivudine (β-l-2′,3′-dideoxy-3′-thiacytidine,
3TC) self-assembles into a base-paired and helically base-stacked
hexagonal structure. Face-to-face and face-to-tail stacked 3TC3TC
dimers base-paired through two hydrogen bonds between neutral cytosines
by either N–H···O or N–H···N
atoms give rise to a right-handed DNA-mimicry of lamivudine with an
unusual highly symmetric hexagonal lattice and topology. In addition,
a base-paired and base-stacked supramolecular architecture of lamivudine
hemihydrochloride hemihydrate was also obtained as a result of our
crystal screenings. This structure is formed through partially face-to-face
stacked lamivudine pairs held together by protonated and neutral fragments.
However, no helical stacking occurs in this structure in which lamivudine
also adopts unusual conformations as the C1′-<i>endo</i> and C1′-<i>exo</i> sugar puckers and cytosine orientations
intermediate between the <i>anti</i> and <i>syn</i> conformations. As a conclusion drawn from the nucleoside duplex,
the hexagonal DNA-mimicry of lamivudine reveals that such double-stranded
helices can be assembled without counterions and organic solvents
but with higher crystallographic symmetry instead, because only water
crystallizes together with lamivudine in this structure
The Continuum in 5‑Fluorocytosine. Toward Salt Formation
5-Fluorocytosine
(5-FC) was crystallized with complementary dicarboxylic
acids, aiming to achieve a controlled synthesis of structures based
on the Δp<i>K</i><sub>a</sub> rule proposed in the
salt–cocrystal continuum study and to provide structural information
helpful in the comprehension of its supramolecularity. Although 5-FC
tends to be basic, p<i>K</i><sub>a</sub> = 3.26, only three
salts are reported. In this way, new 5-FC salts were obtained, the
fumaric, maleic and oxalic ones, all crystallizing in the monoclinic
space group <i>P</i>2<sub>1</sub>/<i>c</i>. In
the 5-FC oxalate and fumarate cases, the acid molecules are placed
on an inversion center in a fashion that each half molecule exhibits
one terminal donor–acceptor site, leading to the constitution
of a 5-FC–acid–5-FC heterodimer. Such a heterodimer
is observed in only one donor–acceptor site of the maleate
of 5-FC, whose acid molecule exhibits a closed chain architecture.
Infrared and Raman spectra recorded for the three compounds complement
the salt characterization on the basis of the extent of proton transfer.
Thermal analysis evidence that the salt formation decreases the melting
point of the new compounds, ranking this molecule as a coformer candidate
to improve the physical properties of other drugs