Curcumin is known as (1E,6E)-1,7-bis(4-hydroxy-methoxyphenyl)-1,6-heptadiene-3,5-dione by the International Union of Pure and Applied Chemistry (IUPAC). Curcumin's chemical formula and molecular weight are C21H20O6 and 368.38 g/mol, respectively. Curcumin is composed of three chemical components: two aromatic ring systems of o-methoxy phenolic groups joined by a seven carbon connector containing an α, β-unsaturated β-diketone molecule.
Curcumin is less soluble in water at acidic and neutral pH levels, although it is soluble in ethanol, alkali, ketone, methanol, acetic acid, chloroform, dimethyl sulfoxide (DMSO), and acetone. Curcumin has a melting temperature of 176 – 177°C and various methoxy substitutions in the diferuloylmethane chemical structure (which is responsible for the yellow coloration), demethoxycurcumin, bisdemethoxycurcumin, and cyclocurcumin (Figure 1) are responsible for many biological and pharmacological differential activities [1].
(Figure 1: Chemical structure of curcumin (A) [(1) b-diketone or keto-enol, (2) phenolic, (3) alkene linker], demethoxycurcumin (B), bisdemethoxycurcumin (C) and cyclocurcumin (D) (Source))
Curcumin is capable of binding to different cellular and molecular entities within the human body and can effectively enable or obstruct biological pathways through proteins, enzymes, metals, lipid layers, and ionic channels, to name a few. Curcumin has been identified to exhibit pleiotropy or having more than one behavior in a suspended microenvironment where the moiety interacts with intra- and extracellular targets via stimuli manipulation (changing pH, enzyme pathways, transcription and growth factors).
(Neuroprotective mechanisms of curcumin in treating Parkinson’s disease (Source))
Despite the presence of as many functional groups and different intermediate and mixed forms that allow curcumin to express its cellular behaviors, a clear understanding of the exact mechanism is still being investigated. Whether it is the acidic proton on the central methyl group (-CH2 at position 1 in Figure 1) or the phenol is a question that remains to be answered. However, curcumin’s behavior in an acidic environment in its diketo form has been theorized and substantiated from research to follow proton transfer via the central methyl group (diketo position 1) – this was theorized by observing the stability of the intermediate carbanion and/or radical intermediates and measuring the reduction potentials as the reaction progressed [2].
References:
Karthikeyan, A., Senthil, N. & Min, T. Nanocurcumin: A Promising Candidate for Therapeutic Applications. Frontiers in Pharmacology vol. 11 Preprint at https://doi.org/10.3389/fphar.2020.00487 (2020).
Barclay, L. R. C. et al. On the antioxidant mechanism of curcumin: Classical methods are needed to determine antioxidant mechanism and activity. Org Lett 2, 2841–2843 (2000).
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