Syntheses, spectroscopy and structures of metal and organic base geminal bisphosphonates

This thesis describes the synthesis, characterisation and structures of new geminal bisphosphonate complexes and ion-pair salts, mainly featuring (4-amino-1-hydroxybutylidene)-1,1-bisphosphonate (alendronate) ions. These include Group 1 (Chapter 2), Group 2 (Chapter 4), first row transition (Appendix 3) and lanthanoid metal (Appendix 1) alendronate complexes. They also include aminium ion-pair salts containing alendronate (Chapter 3) and two other related geminal bisphosphonates (Chapter 5). The Introduction (Chapter 1) discusses the fundamental properties and chemistry of the anions, cations and the bases used, with emphasis placed on alendronic acid and its’ compounds. The Introduction also includes a discussion of some of the biological aspects of geminal bisphosphonic acids. New crystal structures feature supramolecular assembles with extensive hydrogen bonding. The strongest hydrogen bonding occurred between -PO₂(OH)- and the -PO₃²⁻ groups i.e. –O₂P-O-H…O-PO₂- in doubly deprotonated alendronate ions. Presumably, this occurred to partly delocalise the charge on the two phosphonate groups. The alendronate anion showed an exceptional ability to coordinate to metal cations through a variety of different bonding modes, this possibility being alluded to in the Introduction. Geminal bisphosphonate anions have an affinity for metal ions because they are multi-oxygen donors and can be multiply charged. The varied binding modes can lead to polymorphism, exemplified by [Rb(H₄L)(H₂O)].H₂O and [Cs(H₄L)(H₂O)].H₂O (where H₅L = alendronic acid) and variable hydration (e.g. K₂(H₃L).3H₂O and [K(H₃L)(μ-H₂O)₂K(H₂O)₄]). An unusual [Rb(H₄L)(H₅L)].2H₂O structure is described which contained an uncharged alendronic acid moiety. The structure of an unexpected bimetallic complex [Cu₅ (H₂L)₄Na₂(H₂O) ₈].5H₂O, containing a triply deprotonated alendronate ion bound to Cu and Na ions, was elucidated. [Li(H₄L)(H₂O)₂] was a mononuclear structure and all other compounds were coordination polymers. The Group 1 metal complexes are soluble and the growing of crystals was complicated by polymorphism and different hydrate formations. The Group 2, transition and lanthanoid complexes are insoluble in polar solvents making it difficult to grow crystals to use for structural evaluation. This was a major impediment to the initial thrust of the research. The ion-pair aminium alendronate salts were all soluble. None of them were ionic liquids (melting points <100 °C). Although some salts appeared to melt close to 100 °C, this process mainly involved the loss of waters of crystallisation. The aminium salts feature several types of ring motifs which add to their structural stability. Hydrogen bonding also contributed to structural integrity and one salt contained as many as 38 such bonds. The alendronate anion has characteristic infrared absorption bands, of strong intensity, with the symmetric P-O stretching bands near 1040 cm⁻¹ clearly evident. The solid state phosphorus NMR spectra, although complex to interpret, proved a useful tool in identifying different phosphorus environments and in providing evidence that some compounds existed as polymorphs. The geometry of the alendronate anion was essentially unchanged when coordinated to a metal cation.