The first polymorph in the family of nucleobases: a second form of cytosine

Abstract

A new polymorph of cytosine, C4H5N3O, is reported half a century after the report of its first known crystal structure [Barker & Marsh (1964). Acta Cryst. 17, 1581-1587]. Cytosine thus provides the first polymorphic example in the category of parent nucleobases. The new form, denoted (Ib), was observed unexpectedly during an attempt to cocrystallize cytosine with catechol. Form (Ib) crystallizes in the orthorhombic centrosymmetric space group Pccn with two molecules in the asymmetric unit. The previously known form, denoted (Ia), crystallizes in the orthorhombic noncentrosymmetric space group P212121. The cytosine molecule is planar in both forms. Hydrogen-bonding interactions are also similar for both forms. Infinite one-dimensional ribbons composed of cytosine base-pair dimers in R2(2)(8) arrangements are observed in both (Ia) and (Ib). However, the way that the ribbons are packed differs in (Ia) and (Ib). This appears to guide the centrosymmetric versus noncentrosymmetric space-group selection through the formation of an inversion-related motif in polymorph (Ib) and a helical propagation in polymorph (Ia). A few selected polymorphic systems have been gathered from the Cambridge Structural Database to understand possible structural features responsible for achiral molecules adopting centro- and noncentrosymmetric space groups.

Experimental and Computational Hydrate Screening: Cytosine, 5-Flucytosine, and Their Solid Solution

“…Both, cytosine and 5-flucytosine, exhibit polymorphism. The Cambridge Structural Database (CSD) contains each two distinct anhydrate structures for cytosine (CYTSIN and CYTSIN01 correspond to one polymorph, C–I ; CYTSIN02, C–II ) and 5-flucytosine (MEBQEQ01, F–I ; MEBQEQ, F–II ). One monohydrate form is known for cytosine (Refcode family: CYTOSM ,− ).…”

Dapsone Form V: A Late Appearing Thermodynamic Polymorph of a Pharmaceutical

“…conformation (Figure 8) to exploit all experimental conditions that may lead to different solid forms (e.g., [8][9][10][11][12][13][14][15][16][17] ) and there is always the risk of missing relevant forms. The use of CSP as a complementary method to experimental screening can be highly advantageous in identifying putative other forms (e.g.…”

“…Such classic techniques are often adequate to find numerous solid forms for a broad range of substances, but there are always cases where more specialized and/or tailored approaches are required. The vast number of possible experiments that have led to solid forms, which extends beyond the classical methods, − makes it hard to create a recipe for complete confidence that all possible solid-state forms are found and impossible to cover the entire crystallization “space”. Crystallizing the most stable form can be complicated by the fact that this form may show a slow nucleation and growth rate, in contrast to metastable form(s), as seen for 4-aminoquinaldine monohydrate Hy1B° .…”

Two polymorphs of 2,5-dichloro-3,6-bis(dibenzylamino)-p-hydroquinone with flexible dibenzylamino groups

“…Polymorphism has attracted significant interest from both academic and industrial researchers in fields such as pharmaceuticals, foods and pigments, because the differences in the packing arrangements and molecular conformations of polymorphs result in different physicochemical properties in the crystalline state (Bernstein, 1987(Bernstein, , 2002. Therefore, the understanding and prediction of the occurrence of polymorphs has been intensively studied, particularly focusing on molecular structure (Chrobak et al, 2014;Sridhar et al, 2015;Ibragimov et al, 2016). Several structural parameters, such as hydrogen bonding and molecular flexibility, have been suggested as significant factors for polymorphism in molecular crystals (Yu et al, 2000).…”