Designing a Cocrystal of γ‐Amino Butyric Acid

Abstract

Es gehören immer zwei dazu: Eine Strategie für die gezielte Herstellung von Cokristallen (siehe Bild) mit vorbestimmter Struktur beruht auf dem Erkennen und Nutzen spezifischer Wasserstoffbrückenmuster mit der Graphensatz‐Notation ${{{\rm {\rm R}}{{2\hfill \atop 4\hfill}}}}$(8). Dieses supramolekulare Synthon erzeugt systematisch individuelle Viermolekülcluster.

Preparation and Characterization of Carboxylic Acid Adducts of Gabapentin

“…The band at 1645 cm -1 corresponds to (C=O) of carboxylate groups. While similar discussion of 2:1 gabapentin:oxalic acid adducts has been reported [9], the possibility of formation does not prove the synthon has formed as is illustrated by the GABA:oxalic acid study [7,8] which contains the ionized ammonium and carboxylate forms, but does not contain the R4 2 (8) hydrogen bond synthon.…”

“…Compounds containing carboxylic acid functional groups can readily interact with the −NH2 and −COOH fragments of un-ionized gabapentin, or the -NH3 + and -COO  fragments of Zwitterionic gabapentin ( Fig. 1) to form network synthons as seen in previous studies with GABA and gabapentin with carboxylic acids [7][8][9][10]. Melting points of the four known forms of gabapentin are given in Table 1.…”

Diastereomeric Salt Formation by the γ-Amino Acid RS-Baclofen and L-Malic Acid: Stabilization by Strong Heterosynthons Based on Hydrogen Bonds between RNH3+ and COOH/COO– Groups

“…In the related motif Ib, which is observed in RS-BAC, one of the BAC bridges is replaced by an ammonium and a carboxylate group from two additional BAC molecules. Another frequent pattern is motif II, 76 which corresponds to a [2 + 2] cyclic arrangement involving two NH 3 + and two COO − groups from four different BAC molecules. Motif II is observed in RS-BAC and the cocrystals with benzoic and ptoluic acid.…”

“…RS-BAC:ferulic acid hemihydrate exhibits the mixed version of motifs II and III, which was also reported by Wenger and Bernstein for GABA:benzoic acid (Table 4). 76 It is important to mention that motif III is related to the common [R 2 NH 2 + •••Cl − ] 2 pattern (motif IIIb, Scheme 1). 77 Interestingly, in the molecular salts and cocrystals reported so far with BAC, the coformer counterions do not form hydrogen bonding interactions between each other, although organic salts of dicarboxylic acids, where only one COOH group is ionized, frequently form 1D chains or 2D networks through COOH••• − OOC hydrogen bonds.…”

Benefits of cocrystallisation in pharmaceutical materials science: an update

“…For example, Wenger et al used extensive database searches and screening experiments to propose the R 2 4(8) supramolecular synthon as a design element for the construction of solid forms of g-aminobutyric acid and gabapentine held together by charge-assisted hydrogen bonds. [24,25] In some cases, supramolecular synthons responsible for cocrystallisation act as pathways for intermolecular proton transfer. The result is an ionic structure where conventional hydrogen bonds have been transformed into charge-assisted hydrogen bonds.…”