Green synthesis, spectroscopic and theoretical studies on molecular charge-transfer complex of linagliptin with 2, 3-dichloro-5,6-dicyano-1,4-benzoquinone, chloranilic acid and ninhydrin

• Published in: Journal of molecular liquids Vol. 401; p. 124696
• Main Authors: Zaki, Sameera, Ali, Saeeda Nadir, Qayoom, Amtul, Ahmed, Rafiq, Khan, Aiman Rasheed
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-05-2024
• Subjects: AGREE; Charge transfer complex; Chloranilic acid; DDQ; Linagliptin; Ninhydrin; UV–Vis spectrophotometer; DDQ; UV–Vis spectrophotometer; Ninhydrin; AGREE; Linagliptin; Charge transfer complex; Chloranilic acid
• DOI: 10.1016/j.molliq.2024.124696
• EISSN: 1873-3166
• ISSN: 0167-7322

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•Three charge-transfer complexes of LNG with DDQ, ChA, and NIN were synthesized in a green solvent and characterized.•Linear calibration curves for linagliptin with all the complexes were obtained with R2 > 0.997.•The complexes exhibited a 1:1 ratio with DDQ and ChA and a 1:2 ratio with NIN by Job's plot.•Environmental sustainability of the proposed method was evaluated by AES and AGREE tool.•The method proved effective in analyzing LNG in dosage forms, confirming its suitability for pharmaceutical quality control.
Three novel intermolecular proton transfer complexes of an anti-diabetic drug linagliptin were synthesized in methanol with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, chloranilic acid, and ninhydrin as the acceptors. The stoichiometry of the complexes was determined by Job's method of continuous variation. A swift and precise spectrophotometric method was developed and validated for quantitative analysis of linagliptin in its pure form. This method generated linear calibration curves, covering specific concentration ranges of 2.84–28.35, 2.36–21.26, and 9.45–85.06 μg mL−1 for reagents, such as DDQ, chloranilic acid, and ninhydrin respectively. In all instances, the correlation coefficient exceeded 0.997, demonstrating the method's reliability. The Benesi-Hildebrand equation was applied to determine the spectral factors, such as the transition dipole moment, oscillator's strength, molar extinction, ionization potential, resonance energy, and thermodynamic factors, i.e., association constant and Gibb's free energy. The stability of the synthesized charge transfer complexes was confirmed by ensuring that the factors met the approved ranges. Additionally, the synthesized complexes were characterized by FT-IR and thermogravimetric analysis. The environmental friendliness of the newly developed method was assessed using the AGREE tool. A comparison was made between the proposed method and an existing spectrophotometric technique using an analytical eco-scale approach. The proposed method proved effective in analyzing linagliptin in dosage formulations in the presence of potentially interfering excipients confirming its suitability for quality control purposes in pharmaceutical production.