Re-evaluated data of dissociation constants of alendronic, pamidronic and olpadronic acids

Abstract

The dissociation constants of (4-amino-1-hydroxybutylidene)bisphosphonic (alendronic) acid, (3-(dimethylamino)-1-hydroxypropylidene)bisphosphonic (olpadronic) acid and (3-amino-1-hydroxypropylidene)bisphosphonic (pamidronic) acid were obtained in aqueous solutions (0.10 M KCl) and micellar solutions of cetylpyridinium chloride (0.10 M CPC) at 25.0°C. With the exception of the third dissociation constant of alendronic acid, the dissociation constants of alendronic, olpadronic and pamidronic acids in aqueous solutions matched literature data. The possibility of sodium alendronate determination by acid-base titration by NaOH solution was theoretically grounded on the basis of re-evaluated data of alendronic acid dissociation constants.

Systematic Study of the Physicochemical Properties of a Homologous Series of Aminobisphosphonates

“…The following general trend can be found in the results of this study: the lengthening of the CH 2 chain between BP and amino groups decreases the value of the first protonation constant (pKa 5 , amino group) and increases the values of the other protonation constants (phosphonate groups) in most cases ( Table 2 ). The same trend can be seen also in those earlier studies where a comparison is possible, e.g., for all pK a values with compounds 1 and 2 [ 14 , 17 ] and for pKa values of the phosphonate groups with compounds 1 and 2 [ 13 , 18 ] and with compounds 1 and 4 [ 16 ]. The protonation of the ligands is also illustrated in the percentage distribution curves calculated from log β values (see Figure S3 in the Supporting Information ).…”

“…The logK values for compounds 1 , 2 and 4 from earlier studies can be found in literature, but they are not entirely comparable with each other because of the different experimental conditions used (e.g., background electrolyte, ionic strength, temperature or method) [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Although these values vary to some extent for each ligand, they do agree with each other on the whole, taking into consideration the different conditions.…”

“…, pamidronate ( 1 ) was almost freely soluble in water whereas a compound with a longer chain, e.g., n = 10, was virtually insoluble in water and most common organic solvents. Moreover, although pamidronate ( 1 ), alendronate ( 2 ) and neridronate ( 4 ) are in drug use and they have been intensively studied by several groups, there is still some discrepant information, concerning their properties, e.g., there are variations in their pK a values published in the literature [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”

A biocompatible calcium bisphosphonate coordination polymer: towards a metal-linker synergistic therapeutic effect?

“…The ligand is partially deprotonated, and the position of the remaining acidic H atoms was deduced from the combination of pK a values, bond valence calculations (see ESI †; Table S2), solid state NMR data (first principle calculations) and was further confirmed by the analysis of the coordination sphere around the Ca atom and the hydrogen bond network (see below). First, regarding the values of the corresponding pK a (pK a2 = 2.2, pK a3 = 6.4, pK a4 = 10.7, pK a5 = 11.4 27 ) and the synthetic conditions (pH ~7.4), the amine group was considered fully protonated (-NH 3 + ), together with the hydroxyl group (O7H). The remaining H atom was found disordered on the two non-bonded oxygen atoms of the phosphonate groups (O3 and O6).…”

Smart, programmable and responsive injectable hydrogels for controlled release of cargo osteoporosis drugs

“…Furthermore, the bands assigned to the R-(CH 2 ) x -NH 3 + moiety (in the regime >3000 cm −1 ) broaden and are undetectable in the dried gel spectra. Regarding the protonation state of the BPs, it is certain (from literature reports 36 – 38 ) that at pH 7 (the pH of the internal gel regions) each phosphonate moiety is mono-deprotonated (–PO 3 H − ), and (for the aminoalkyl BPs) the amine moiety is protonated (R-(CH 2 ) x -NH 3 + ).…”