Alkoxide coordination of iron(III) protoporphyrin IX by antimalarial quinoline methanols: a key interaction observed in the solid-state and solution

Dalton Transactions : an International Journal of Inorganic Chemistry
Johandie GildenhuysKatherine A de Villiers

Abstract

The quinoline methanol antimalarial drug mefloquine is a structural analogue of the Cinchona alkaloids, quinine and quinidine. We have elucidated the single crystal X-ray diffraction structure of the complexes formed between racemic erythro mefloquine and ferriprotoporphyrin IX (Fe(iii)PPIX) and show that alkoxide coordination is a key interaction in the solid-state. Mass spectrometry confirms the existence of coordination complexes of quinine, quinidine and mefloquine to Fe(iii)PPIX in acetonitrile. The length of the iron(iii)-O bond in the quinine and quinidine complexes as determined by Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy unequivocally confirms that coordination of the quinoline methanol compounds to Fe(iii)PPIX occurs in non-aqueous aprotic solution via their benzylic alkoxide functional group. UV-visible spectrophotometric titrations of the low-spin bis-pyridyl-Fe(iii)PPIX complex with each of the quinoline methanol compounds results in the displacement of a single pyridine molecule and subsequent formation of a six-coordinate pyridine-Fe(iii)PPIX-drug complex. We propose that formation of the drug-Fe(iii)PPIX coordination complexes is favoured in a non-aqueous environment, such as that found in l...Continue Reading

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Citations

Mar 7, 2017·Chemistry : a European Journal·Alistair J FieldingFyaz M D Ismail
Oct 10, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Anjana M D S Delpe AcharigeMarcus C Durrant
Oct 13, 2017·Journal of Applied Crystallography·Ruben A DilanianBrian Abbey
Feb 24, 2021·Journal of Medicinal Chemistry·Aloysus LawongMargaret A Phillips
Oct 9, 2018·European Journal of Medicinal Chemistry·Fabrizio P L'abbateTimothy J Egan
May 14, 2021·Accounts of Chemical Research·Katherine A de Villiers, Timothy J Egan

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