Protonation-deprotonation and structural dynamics of antidiabetic drug metformin
| Autor: | Fernando Pflüger, Belén Hernández, Régis Cohen, Mahmoud Ghomi, Sergei G. Kruglik |
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| Rok vydání: | 2015 |
| Předmět: |
Drug
Stereochemistry media_common.quotation_subject Chemistry Pharmaceutical Clinical Biochemistry Population Biophysics Pharmaceutical Science Protonation Spectrum Analysis Raman Protein Structure Secondary Analytical Chemistry Deprotonation Computational chemistry Drug Discovery medicine Molecule Animals Humans Hypoglycemic Agents Technology Pharmaceutical Amino Acids education Spectroscopy Serum Albumin media_common Platinum education.field_of_study Aqueous solution Chemistry DNA Hydrogen-Ion Concentration Metformin Diabetes Mellitus Type 2 Density functional theory Cattle Protons medicine.drug |
| Zdroj: | Journal of pharmaceutical and biomedical analysis. 114 |
| ISSN: | 1873-264X |
| Popis: | Since the late 1950s, metformin is the worldwide first-line pharmacologic treatment for type 2 diabetes. Beyond the fact that the mode of action of this drug has always been very difficult to elucidate, little is known about its physicochemical properties in aqueous solution. Herein, we focus on the protonation-deprotonation features of metformin by using jointly Raman scattering and theoretical calculations. Vibrational markers evidence the fact that within a wide pH interval extended at either side of the physiological one, i.e. ∼7 ± 4, metformin is mainly monoprotonated. Although the biprotonated form appears as major population at very low pH values (1.5), Raman markers of neutral species do not dominate even at very high pH values (13), presumably because of the extreme basicity of metformin as described by recent NMR measurements. Density functional theory calculations using both explicit and implicit hydration models, have led to presume a possible coexistence of two possible monoprotonated forms in aqueous environment. In conclusion, the biophysical features of this molecule and the amount used in clinical practice might certainly explain the pleiotropic actions toward several targets where metformin could be a permanent cationic partner, a proton donor/acceptor, as well as a good candidate for stabilizing the so-called π→π interactions. |
| Databáze: | OpenAIRE |
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