Pressure-controlled aggregation in carboxylic acids. A case study on the polymorphism of bromochlorofluoroacetic acid

Abstract

Pressure induces different hydrogen-bonding patterns in the polymorphs of bromochlorofluoroacetic acid, CBrClFCOOH, by affecting the balance between secondary intermolecular interactions involving halogen and oxygen atoms. In polymorph a a pattern of the molecules syn-syn H-bonded into catemers is strongly corrugated, up to the limit imposed by steric hindrances between the neighboring chain members, whereas in polymorph b the molecules are H-bonded into dimers. No phase transition between the catemeric and dimeric CBrClFCOOH polymorphs, despite the over-pressurizing phase a by over 1.3 GPa into the stability region of phase b, demonstrates that the preference for dimeric and catemeric forms of carboxylic acids may be impossible for detection as classical solid-state phase transitions, without completely dissolving or melting these compounds and avoiding their nucleation. The smaller volume of the b phase, and hence its high-pressure stability, has been rationalized by more freedom of the 0-D dimers to adjust their positions in the crystal structure, compared to the 1-D catemers. The conformational limitations of the carboxylic-acid aggregates are consistent with the survey of all carboxylic-acid structures determined so far.

Structural, spectroscopic and theoretical studies of dimethylphenyl betaine complex with two molecules of 2,6-dichloro-4-nitro-phenol

“…the is not confirmed by OAHÁ Á ÁO angles, which are about 152°. However, the Donohue angles [33][34][35] clearly indicate that the O(3)HÁ Á ÁO(1) bond is more relaxed: the C(11)AO(3)Á Á ÁO(1) angle is 128.4(3)°and C(10)AO(1)Á Á ÁO(3) 121.7(3)°, i.e. close to the optimal opening of about 120°, consistently with the oxygen atoms hybridization [36,37].…”

Unusual seeding effect in the liquid-assisted high-pressure polymorphism of chlorpropamide

“…Highpressure has been recently proposed as a tool to obtain new polymorphs of pharmaceuticals, which, if preserved on flashdecompression, can be used as seeds for mass-crystallization at ambient conditions [19][20][21][22][23] . However, the control of highpressure polymorphism is not a trivial task [19,[24][25][26][27][28] . The role of kinetic factors known to influence crystallization at ambient conditions increases enormously at high pressure, when molecular motions are even more restricted, the sample is located in a confined space of a gasket hole, the pressuretransmitting fluid is not mixed and is often viscous, so that diffusion and convection processes are hindered.…”

Polymorphism and Solvatomorphism 2009

“…150 The effect of pressure on the hydrogenbonding patterns in two polymorphs of bromochlorofluoroacetic acid has been studied, with the aim of obtaining information on the bonding preferences for dimer and catemer motifs. 151 Given the importance of amorphous pharmaceutical solids in drug delivery, studies of the stability of the amorphous phase and amorphous-to-crystalline phase transitions remain of importance. The lowfrequency Raman spectrum (5-250 cm −1 ) of the crystalline and amorphous states of indomethacin has been investigated, and was used to demonstrate the high sensitivity inherent in the method with respect to the detection and identification of the onset of crystallization.…”