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Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
Solution studies of dinuclear polyamine-linked platinum-based antitumour complexes.
Rasha A Ruhayel1, Ibrahim Zgani, Susan J Berners-Price
1School of Biomedical, Biomolecular & Chemical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia.
Dalton Transactions (Cambridge, England : 2003)
|March 9, 2011
Summary
This study investigates platinum-based anticancer complexes BBR3007 and BBR3610, revealing their aquation profiles and acid dissociation constants. The findings provide insights into the behavior of these novel platinum drugs in biological systems.
Area of Science:
- Inorganic Chemistry
- Medicinal Chemistry
- Biochemistry
Background:
- Platinum-based drugs are crucial in cancer chemotherapy.
- Understanding the aquation and reactivity of platinum complexes is key to their efficacy.
- Novel dinuclear platinum complexes with polyamine linkers offer potential therapeutic advantages.
Purpose of the Study:
- To determine the aquation profiles of two novel dinuclear platinum-based anticancer complexes, BBR3007 and BBR3610.
- To quantify the rate constants for hydrolysis and acid dissociation of coordinated aqua ligands.
- To evaluate the influence of linker backbone structure on complex reactivity and aquation behavior.
Main Methods:
- Utilized 2D [(1)H, (15)N] HSQC NMR spectroscopy to probe aquation profiles.
- Measured aquation and anation rate constants under specific conditions (15 mM NaClO(4), pH 5.4, 298 K).
- Determined acid dissociation constants (pK(a)) for aquated derivatives and compared with related complexes.
Main Results:
- Reported specific rate constants for aquation (k(1)) and anation (k(-1)) for BBR3007 and BBR3610.
- BBR3610 exhibited a higher pK(1) (4.54) compared to BBR3007 (3.12) and a trinuclear analogue (3.44), indicating less aquation at equilibrium.
- Aquated forms of BBR3007 and BBR3610 showed higher pK(a) values (5.92) than related dinuclear and trinuclear complexes, attributed to macrochelate formation.
Conclusions:
- The linker backbone significantly influences the aquation equilibrium and reactivity of dinuclear platinum complexes.
- BBR3610 is the least aquated complex at equilibrium among those studied, suggesting potentially different in vivo behavior.
- Higher pK(a) values in polyamine-linked complexes are linked to macrochelate formation, impacting their interaction with biological targets.
