Synthesis, characterization and crystal structure of a new organic salt of antidiabetic drug metformin resulting from a proton transfer reaction

Ghasemi, Fatemeh; Rezvani, Ali Reza; Ghasemi, Khaled; Razak, Ibrahim Abdul; Rosli, Mohd Mustaqim

doi:10.1016/j.molstruc.2019.05.040

Cited by 3 publications

(1 citation statement)

References 41 publications

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“…The presence of hydrogen bonds between proton donors and acceptors plays an important role with respect to the formation and stability of 1:1 or 2:1 proton-transfer salts (Smith & Wermuth, 2010a,b, 2011, 2013c, 2014Smith et al, 2007Smith et al, , 2008Subha et al, 2022). Various organic bases can receive a proton and become protonated cations, examples being pyrazine (Lengyel et al, 2019), piperazine (Ding et al, 2014;Muslim et al, 2021;Subha et al, 2022), imidazole (Massey et al, 2016;Khan et al, 2021), indole (Ma et al, 2018), quinoline (Belombe et al, 2011;Li et al, 2012;Khan et al, 2022), 1,2,4-triazole and other azoles (Luo et al, 2011;Massey et al, 2012;Tucker et al, 2015;Singh et al, 2021), hydrazine (Smith et al, 2009), benzamidine (Portalone, 2010(Portalone, , 2014Irrera et al, 2012), sulfamethazine (Padrela et al, 2019), guanidine (Smith et al, 2007;Ghasemi et al, 2019), adenine (Sedghiniya et al, 2019) and amines (Rosokha et al, 2006;Zhang & Zhu, 2007;Ding et al, 2012Ding et al, , 2013Smith & Wermuth, 2013a, 2016Shmukler et al, 2019;El-Dissouky et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Proton-transfer salts of diphenylphosphinic acid with substituted 2-aminopyridine: crystal structure, spectroscopic and DFT studies

Yuan

Zhang

et al. 2023

Acta Crystallogr C

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Three proton-transfer salts of diphenylphosphinic acid (DPPA) with 2-amino-5-(X)-pyridine (AMPY, X = Cl, CN or CH3), namely, 2-amino-5-chloropyridinium diphenylphosphinate, C5H6ClN2 +·C12H10O2P− (1, X = Cl), 2-amino-5-cyanopyridinium diphenylphosphinate, C6H6N3 +·C12H10O2P− (2, X = CN), and 2-amino-5-methylpyridinium diphenylphosphinate, C6H9N2 +·C12H10O2P− (3, X = CH3), have been synthesized and characterized by FT–IR and 1H NMR spectroscopy, and X-ray crystallography. The crystal structures of compounds 1–3 were determined in the space group P\overline{1} for 1 and 2, and C2/c for 3. All three compounds contain N—H...O hydrogen-bonding interactions due to proton transfer from the O=P—OH group of DPPA as donor to the pyridine N atom of AMPY as acceptor. The proton transfer of compounds 1–3 was also verified by 1H NMR and FT–IR spectroscopy. The stoichiometry of all three proton-transfer salts was determined to be 1:1 and the Benesi–Hildebrand equation was applied to determine the formation constant (K CT) and the molar extinction coefficient (ɛCT) in each case. Theoretical density functional theory (DFT) calculations were performed to investigate the optimized geometries, the molecular electrostatic potentials (MEP) and the highest occupied molecular orbitals (HOMO) and lowest unoccupied molecular orbitals (LUMO) of all three proton-transfer salts. The results showed good agreement between the experimental data and the DFT computational analysis.

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Section: Introductionmentioning

confidence: 99%

Proton-transfer salts of diphenylphosphinic acid with substituted 2-aminopyridine: crystal structure, spectroscopic and DFT studies

Yuan

Zhang

et al. 2023

Acta Crystallogr C

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Salts or complexes? Factors affecting the type of binding of biogenic organic amines by carboxyl derivatives of 1,1′-dinaphthylmethanes and calix[4]resorcinarenes

et al. 2022

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Determination of metformin bio-distribution by LC-MS/MS in mice treated with a clinically relevant paradigm

Chaudhari

Wang

et al. 2020

PLoS ONE

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Metformin, an anti-diabetes drug, has been recently emerging as a potential "anti-aging" intervention based on its reported beneficial actions against aging in preclinical studies. Nonetheless, very few metformin studies using mice have determined metformin concentrations and many effects of metformin have been observed in preclinical studies using doses/ concentrations that were not relevant to therapeutic levels in human. We developed a liquid chromatography-tandem mass spectrometry protocol for metformin measurement in plasma, liver, brain, kidney, and muscle of mice. Young adult male and female C57BL/6 mice were voluntarily treated with metformin of 4 mg/ml in drinking water which translated to the maximum dose of 2.5 g/day in humans. A clinically relevant steady-state plasma metformin concentrations were achieved at 7 and 30 days after treatment in male and female mice. Metformin concentrations were slightly higher in muscle than in plasma, while,~3 and 6-fold higher in the liver and kidney than in plasma, respectively. Low metformin concentration was found in the brain at~20% of the plasma level. Furthermore, gender difference in steady-state metformin bio-distribution was observed. Our study established steady-state metformin levels in plasma, liver, muscle, kidney, and brain of normoglycemic mice treated with a clinically relevant dose, providing insight into future metformin preclinical studies for potential clinical translation.

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Synthesis, characterization and crystal structure of a new organic salt of antidiabetic drug metformin resulting from a proton transfer reaction

Cited by 3 publications

References 41 publications

Proton-transfer salts of diphenylphosphinic acid with substituted 2-aminopyridine: crystal structure, spectroscopic and DFT studies

Proton-transfer salts of diphenylphosphinic acid with substituted 2-aminopyridine: crystal structure, spectroscopic and DFT studies

Salts or complexes? Factors affecting the type of binding of biogenic organic amines by carboxyl derivatives of 1,1′-dinaphthylmethanes and calix[4]resorcinarenes

Determination of metformin bio-distribution by LC-MS/MS in mice treated with a clinically relevant paradigm

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