Epitaxial Retrieval of a Disappearing Polymorph

Abstract

Recrystallization of [PdCl2([9]aneS2O)] ([9]aneS2O = 1-oxa-4,7-dithiacyclononane), 1, and [PtCl2([9]aneS2O)], 2, by diffusion of Et2O vapor into solutions of the complexes in MeNO2 yielded three phases of 1 and two phases of 2. The known phase of 1, herein designated α-1, was obtained under ambient conditions. A second phase, designated β-1, was initially also obtained by this method; however, following the advent of a third phase, γ-1, all subsequent efforts over a period of a year to crystallize β-1 yielded either γ-1, obtained by carrying out the recrystallization at elevated temperature, or α-1, commonly found throughout the study. This persistent absence of a phase which could initially be crystallized with ease led us to the conclusion that β-1 was an example of a “disappearing polymorph”. The first phase obtained of 2, designated α-2, was obtained by recrystallization under ambient conditions and is isomorphous and isostructural with α-1. The second phase β-2 was obtained by slight elevation of the recrystallization temperature and was found to be isomorphous and isostructural with β-1. Subsequently, β-2 was used to seed the growth of the disappearing polymorph β-1. No third phase of 2 (γ-2) has been isolated thus far.

High-pressure studies of three polymorphs of a palladium(II) oxathioether macrocyclic complex

“…This transformation is in marked contrast to the destructive partial ! phase transition observed upon the application of anisotropic pressure, for example when cutting these crystals (Tidey et al, 2015). The absence of such a destructive transformation in this study is likely due to the isotropic application of pressure resisting the necessary expansion along certain vectors that would be required for the aligned dimeric motifs in the layered packing of -(1) to rotate relative to one another and give rise to the herringbone packing of -(1) (Fig.…”

“…The complex [PdCl 2 ([9]aneS 2 O)] [(1), Scheme 1] exhibits polymorphism with three phases hitherto observed, the details of which have already been reported (Tidey et al, 2015). The phase adopts the endodentate conformation and was calculated as being the most thermodynamically stable.…”

“…Complex (1) was prepared as described by Tidey et al (2015). Crystals of -(1) were obtained by diffusion of diethyl ether vapour into a solution of the complex in CH 3 NO 2 at 293 K. Crystals of -(1) were obtained by epitaxial growth off an isomorphous phase of [PtCl 2 ([9]aneS 2 O)] as previously reported (Tidey et al, 2015). Crystals of -(1) were obtained by diffusion of diethyl ether vapour into a solution of the complex in CH 3 NO 2 at 308 K.…”

“…Structures for the ambient pressure phases have been reported previously (Lucas et al, 1997;Tidey et al, 2015), but it is helpful to highlight certain features. Details of the unit-cell parameters at ambient temperature and pressure for the phases discussed in this article are given in Table 1.…”

Perils of Polymorphism: Size Matters

“…Originally prescribed in capsule form with no requirement for refrigeration, the initially developed form of ritonavir was found to convert to a more stable and less soluble polymorph, reducing its bioavailability and forcing Abbot Laboratories to reformulate it at considerable cost . Moreover, the term “disappearing polymorphs”, articulated in 1995 by Dunitz and Bernstein, refers to the formation of a new polymorph that can exclude the nucleation of one previously observed, and strategies for their recovery are now beginning to appear . As Dunitz and Bernstein noted, polymorphism is common, but usually only found when time is spent searching for it; yet a common compound like naphthalene that has been crystallized often and under wide‐ranging conditions, still only exists in one crystal form at ambient conditions.…”