Solid-state NMR of bisphosphonates adsorbed on hydroxyapatite

Großmann, G.; Grossmann, André; Ohms, G.; Breuer, Eli; Chen, Ravit; Golomb, Gershon; Cohen, Hagit; Hägele, Gerhard; Classen, R.

doi:10.1002/(sici)1097-458x(200001)38:1<11::aid-mrc597>3.0.co;2-v

Cited by 26 publications

(23 citation statements)

References 18 publications

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“…34 Using magic angle spinning, Grossman et al were able to distinguish between pure BPs and those specifically adsorbed to HAP. This capability allowed them to estimate the molar ratio of surface-adsorbed to nonadsorbed phosphonates.…”

Section: Resultsmentioning

confidence: 99%

Bisphosphonate binding affinity as assessed by inhibition of carbonated apatite dissolution in vitro

Henneman

Nancollas

Ebetino

et al. 2007

J Biomedical Materials Res

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Bisphosphonates (BPs), which display a high affinity for calcium phosphate surfaces, are able to selectively target bone mineral, where they are potent inhibitors of osteoclast-mediated bone resorption. The dissolution of synthetic hydroxyapatite (HAP) has been used previously as a model for BP effects on natural bone mineral. The present work examines the influence of BPs on carbonated apatite (CAP), which mimics natural bone more closely than does HAP. Constant composition dissolution experiments were performed at pH 5.50, physiological ionic strength (0.15M) and temperature (37°C). Selected BPs were added at (0.5 × 10 −6 ) to (50.0 × 10 −6 )M, and adsorption affinity constants, K L , were calculated from the kinetics data. The BPs showed concentrationdependent inhibition of CAP dissolution, with significant differences in rank order zoledronate > alendronate > risedronate. In contrast, for HAP dissolution at pH 5.50, the differences between the individual BPs were considerably smaller. The extent of CAP dissolution was also dependent on the relative undersaturation, σ, and CAP dissolution rates increased with increasing carbonate content. These results demonstrate the importance of the presence of carbonate in mediating the dissolution of CAP, and the possible involvement of bone mineral carbonate in observed differences in bone affinities of BPs in clinical use.

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Section: Resultsmentioning

confidence: 99%

Bisphosphonate binding affinity as assessed by inhibition of carbonated apatite dissolution in vitro

Henneman

Nancollas

Ebetino

et al. 2007

J Biomedical Materials Res

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“…Concurrently with this work, the absorption of certain BPs on HAP was studied by solid-state NMR spectroscopy [36]. Due to the broadness of the sig-nals obtained in the solid state, this method is limited to compounds having 31 P chemical shifts sufficiently different from that of HAP.…”

Section: Figurementioning

confidence: 99%

“…The molar ratio of phosphonates adsorbed on hydroxyapatite determined by 31 P spectra without cross-polarization (CP) was found to be approximately twice as high for geminal BPs than for 1,1-dihydroxypolymethylene-1,1-bisphosphonates. Interestingly, disodium 1,1-dihydroxypolymethylene-1,1-bisphosphonates in the solid state showed characteristic 13 C chemical shifts, which were indicative of either odd or even numbers of CH 2 groups [36].…”

Section: Figurementioning

confidence: 99%

Long-chain functional bisphosphonates: synthesis, anticalcification, and antiresorption activity

Chen¹,

Schlossman²,

Breuer³

et al. 2000

Heteroatom Chem.

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Bisacylphosphonates have previously been shown to possess in vitro activity with regard to hydroxyapatite (HAP) formation and dissolution, and in vivo on tissue calcification and bone resorption. This work was aimed at elucidating the role of the keto groups in the biological activity of these compounds. For this purpose, we have synthesized a series of long‐chain bisphosphonates possessing different functional groups adjacent to the phosphonic functions and examined them in some in vitro and in vivo models. The functional groups introduced into the newly synthesized bisphosphonates (hydroxyl, amide, and difluoromethylene) were chosen as to represent certain isolated aspects of the keto groups in the original compounds. None of the functional groups introduced into the long chain bisphosphonates bestowed higher activity on the molecules than the carbonyl groups. The unique effect of the α‐keto groups in rendering long‐chain bisphosphonates active is presumably attained through a combination of chelating ability with sufficiently low pKa values to enable the bisacylphosphonate molecules to be fully ionized at physiological pH. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:470–479, 2000

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“…Physicochemical studies that use well‐crystalized noncarbonated hydroxyapatite [HA: Ca 10 (PO 4 ) 6 (OH) 2 ] as a bone model in BPs binding are numerous . Within this type of HA two different coordination environments of Ca 2+ were identified: Ca(1) (nine‐oxygen coordination sphere) and Ca(2) (six oxygens); these are depicted in Figure .…”

Section: Introductionmentioning

confidence: 99%

“…The authors attributed this to the ability of BPs to change their conformation to better match the crystal structure of HP. The changes in charge were postulated to be overcompensated by conformational changes . Computational modeling used for studying risedronate‐related series of N‐BPs revealed the presence of stereospecific recognition events which involve the nitrogen atom (Figure ) .…”

Section: Introductionmentioning

confidence: 99%

Interactions between Clinically Used Bisphosphonates and Bone Mineral: from Coordination Chemistry to Biomedical Applications and Beyond

Gałęzowska

2018

ChemMedChem

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Bisphosphonates (BPs) are well-established, widely used first-choice drugs for bone-related diseases and are one of the few classes of molecules for selective bone targeting. Their binding to calcium cations within hydroxyapatite (HA) is a key physicochemical event that takes place on the bone surface. It is the starting point for a cascade of biochemical reactions and cellular effects that lead to the pharmacological activity of BPs. The phenomenon has been known for years, yet its physicochemical nature is still not fully understood. In particular, the adsorption/release processes and structure-function relationships of BPs remain to be clarified. These are elementary, yet crucial factors, which should influence the design and development of new delivery tools or drugs with improved characteristics. This review summarizes the current understanding of the chemical interactions between clinically used BPs and bone mineral, starting from basic Ca coordination chemistry through to interactions with hydroxyapatite, nanocrystalline apatites, and natural bone mineral.

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Solid-state NMR of bisphosphonates adsorbed on hydroxyapatite

Cited by 26 publications

References 18 publications

Bisphosphonate binding affinity as assessed by inhibition of carbonated apatite dissolution in vitro

Bisphosphonate binding affinity as assessed by inhibition of carbonated apatite dissolution in vitro

Long-chain functional bisphosphonates: synthesis, anticalcification, and antiresorption activity

Interactions between Clinically Used Bisphosphonates and Bone Mineral: from Coordination Chemistry to Biomedical Applications and Beyond

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