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 ΔpKa 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, pKa = 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 P21/c. 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.