Faculty of Natural and Agricultural Sciences
School of Physical Sciences
Department of Chemistry
Selected Highlights from Research Findings
The bone is one of the most preferential metastatic target sites for several cancers, including breast, prostate, and lung cancer because it possesses unique biological features that enable circulating cancer cells to home, survive and proliferate.
Radiopharmaceuticals, such as 153Sm-EDTMP, have produced satisfactory results in pain palliation therapy Intravenous radioisotopes such as 89Sr and 153Sm have been used to treat bone cancer in radiation therapy. The mechanism by which these radioisotope-containing bisphosphonates (BPs) lessen the bone cancer pain is not yet known.
The main component of the bone is the hydroxyapatite (HA). The overall structure of any BP might be written as H2O3P- (R1) C (R2)-PO3H2 with R1 being mostly OH-group. BPs show extremely high affinity toward HA due to the presence of the two groups, –PO3H2.
It is accepted that the bisphosphonates’ ability to bind the bone and their anti-resorptive ability (or potency) depend on the nature of the groups attached to the central carbon atom. BPs containing a primary nitrogen atom in the R2 group (e.g. in 1–hydroxyl–3–aminopropilydene diphosphonic acid, APD) are more potent than non-nitrogen bisphosphonates (e.g. 1-hydroxy-ethylene-diphosphonic acid (HEDP) where R2 = –CH3).
We recently embarked on extensive studies of HEDP and APD by electroanalytical (solution equilibria), spectroscopic (interactions of BPs with HA(s) by Raman), and computational (modelling, MM and MD) techniques.
A newly developed concept of virtual thermodynamic potential, computed from non-equilibrium and dynamic polarographic data, was used to model the solution composition (prediction of metal complexes formed) and computing stability constants of identified species.
Results obtained by us in modelling and optimisation operations (involving virtual potentials) for the APD-Cd(II) and APD-Pb(II) systems are in good agreement with other data reported by us earlier for the HEDP-Cd(II) system where we used a “traditional” methodology. Also, results generated from virtual potentials are in good agreement with Raman Spectroscopic studies. From results obtained we came to the conclusion that there is no evidence to support increased potency of APD by role the –CH2-CH2-NH2 chain might play in the complex formation with a central metal ion.
We claim that this chain is not involved in complex formation reactions at blood plasma pH (just above 7). This opens up a new chapter in interpretation of the role of the R2 group in the increase (or decrease) in activity (potency) of radiopharmaceuticals. Our intention is to computationally model the interactions between the bone (HA) and BPs in order to understand the variation in their potency as a function of the chemical structure of the R2 group.
Virtual potential might be seen as quite an unusual concept, but we are making it clear (by results generated) that without the use of it, it would be impossible to interpret experimental data rigorously. We hope that with time, the concept (theory) of virtual thermodynamic potential will find its place in academic textbooks, but more importantly, will be used daily by many scientists working in the field, and not only us
Contact person: Prof I Cukrowski.
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