Impact of mono- and disubstitution on the colorimetric dynamic covalent switching chalcone/flavanone scaffold

Abstract

The effect of aryl substitution on various aspects of the interconversion of ortho-hydroxychalcones and flavanones has been studied using multiple spectroscopic techniques. Derivatization of the core scaffold predictably alters the midpoint pH of this equilibration process suggesting its viability for application as a functional colorimetric molecular switch.

Facile One-Pot Synthesis of Flavanones Using Tetramethylguanidinum-Based Ionic Liquids as Catalysts

“…On the basis of the above-mentioned results and the previous literatures [8,16], we proposed a plausible mechanism for the one-pot synthesis of flavanone (Fig. 1).…”

“…It was demonstrated that these basic catalysts induced high conversions of 2 0 -hydroxyacetophenone but their selectivities of flavanone were relatively low (Entries [6][7][8][9]. This shows that the Claisen-Schmidt condensation reaction is easily performed in the presence of strong basic catalysts [16], but the second step of the interconversion of 2 0 -hydroxychalcone to flavanone is hard to carry out. Moreover, it was indicated that the substituent on phenolate anion had an obvious impact on reaction selectivity.…”

Extended Aromatic and Heteroaromatic Ring Systems in the Chalcone–Flavanone Molecular Switch Scaffold

“…Between these pH values there is rapid interconversion, with equilibrium concentrations shifting as a function of pH. The midpoint pH is defined as the pH at which there is a 1:1 ratio of chalcone and flavanone in solution, and this metric has been used to compare structural derivatives of the chalcone/flavanone switch. , The midpoint pH can be conveniently obtained by analyzing the sigmoidal curve formed by plotting the measured UV/vis absorbance vs pH as we have outlined in our previous works …”

“…ortho -Hydroxychalcone ( 1a ) is a naturally occurring molecule that can undergo reversible isomerization to its flavanone isomer ( 2a , Figure ). o- Hydroxychalcone/flavanone isomerization has been well-studied in the past, − but its utility as a covalent molecular switch scaffold has only recently been explored. , The most important feature of this scaffold is that it incorporates the reversible formation of a covalent bond. The presence of this reversible covalent bond instills rigidity to the molecule and creates a truly binary switching system.…”

“…The parent scaffold has a midpoint pH of 11.46; to this point, we have been able to depress this value to as low as 10.26 . Ideally, the chalcone/flavanone interconversion would take place much closer to neutral pH, as this would enable the facile application of this switch in the biological realm in manners similar to existing switches.…”