Elucidating structural patterns in hydrogen bond dense materials: a study of ammonium salts of (4-aminium-1-hydroxybutylidine)-1,1-bisphosphonic acid

Forsyth, Craig M.;Greenhill, Neil B.;Junk, Peter C.;Deacon, Glen B.

Abstract

The syntheses and structures of ammonium salts of the active pharmaceutical agent (4-aminium-1-hydroxybutylidine)-1,1-bisphosphonic acid (alendronic acid, LH5) have been examined. Three deprotonation states of the parent acid were achieved i. e. LH4−, LH32− and LH23−, and crystallisation gave a total of six different structural phases including [NH4][LH4] ⋅ 2(H2O) as two polymorphs 1 a and 1 b, two hydrates of [NH4]2[LH3] ⋅ x(H2O), x=3 (2), x=6 (3), [NH4]5[LH3][LH2] ⋅ 8(H2O) (4) and [NH4]3[LH2] ⋅ 3(H2O) (5). The crystal structures obtained, along with that of the parent acid, enable a direct comparison of competing supramolecular synthons, involving phosphonate-phosphonate O−H⋅⋅⋅O and ammonium-phosphonate N−H⋅⋅⋅O hydrogen bonds, in a series displaying progressively decreasing P-OH with concomitantly increasing RNH3+ moieties. Indeed, the structures show some consistent connectivity patterns of the alendronate units, which thus assemble into substructures such as 2-D sheets (LH5 ⋅ H2O, 1 a), zig-zag chains (2, 5) or ladder-like arrays (3, 4). The occurrence of these motifs appears to correlate with the ionisation level of the parent acid.

Journal

Zeitschrift fuer Anorganische und Allgemeine Chemie

Publication Name

Zeitschrift fuer Anorganische und Allgemeine Chemie

Volume

648

ISBN/ISSN

1521-3749

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Wiley-Blackwell

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DOI

10.1002/zaac.202100305