Heidi HalbwirthProf. Amy Howell
Dr. Stefan Martens
Dr. Fulvio Mattivi
Dr. Irene Mueller‐Harvey
Prof. Stéphane Quideau
Prof. Jess Dreher Reed
Dr. Erika Salas
Prof. Juha‐Pekka Salminen
Prof. Kathy Schwinn
Dr. David Vauzour
Prof. Kristiina Wähälä
1 Achieving Complexity at the Bottom Through the Flavylium Cation‐Based Multistate : A Comprehensive Kinetic and Thermodynamic Study
Johan Mendoza and Fernando Pina
Department of Chemistry, Nova School of Science and Technology, Caparica, Portugal
1.1 Introduction
Complexity is ubiquitous in biological systems. The main strategy to study complexity has been carried out using a top‐down approach. Though the top‐down approach the simpler components of the complex systems are identified, and whenever possible, up to the molecular level. In contrast, supramolecular chemistry, a concept well established and recognized after the 1987 Nobel Prize awarded to Donald J. Cram, Jean‐Marie Lehn, and Charles J. Pedersen, is a bottom‐up approach (Figure 1.1). Supramolecular chemistry studies how molecules interact to form higher‐dimension entities and tends to fill the gap between “classical chemistry” and biology (Lehn, 1995).
A beautiful example of supramolecular chemistry is the structure of the metalloanthocyanin that gives color to Commelina communis (Kondo et al. 1992; Yoshida et al. 2009). An anthocyanin, a flavone, and a metal ion in a ratio 6:6:2 are organized into two parallel plans, each one containing three anthocyanins, three flavones, and one metal ion that organizes the space Figure 1.1.
There is an alternative to achieve complexity that we coin metamorphosis (Petrov et al. 2012). When a molecule (generator) is able to be transformed into other molecules by means of successive conversions and as a response to external stimuli, new molecules are formed. The complexity results from the number of the species and everything takes place at the bottom.
The pH‐dependent multistate of species of anthocyanins and related compounds is a paradigm of the metamorphosis concept; see Scheme 1.1.
1.2 Flavylium Cation as a Metamorphosis Generator
The flavylium cation, AH+, is the most stable species at very low pH values, in anthocyanins generally for pH<1. The system is conveniently studied by direct pH jumps when base is added to the flavylium cation, and reverse pH jumps, defined as addition of acid to equilibrated solutions at higher pH values. After a direct pH jump to moderately acidic pHs, the flavylium cation equilibrates in microseconds with quinoidal base, A eq. (1). The next step is the formation of the hemiketal, B, through the hydration of AH+ (min) eq. (2), followed by the ring opening to form cis‐chalcone, Cc, (ms) eq. (3). The fact that the quinoidal base does not open in acidic medium is a breakthrough discovery (Brouillard and Dubois 1977) crucial for the comprehension of anthocyanins and related compounds systems. The Cc isomerization to trans‐chalcone, Ct, in anthocyanins takes place in several hours eq. (4). When the system is equilibrated in moderately acidic pH values, a reverse pH jumps restores the flavylium cation. The following set of equilibrium reactions accounts for the system:
Figure 1.1 Sketch of the metalloanthocyanin responsible for the color in Cummelina communis. The building blocks self‐associate to create the supramolecule in a bottom‐up approach.
Source: Courtesy of Prof. Kumi Yoshida.
Scheme 1.1 The metamorphosis concept in biology and in chemistry applied to anthocyanins and related compounds in acidic medium.
Source: Reproduced from Mendoza et al. (2018), with permission.
A few years ago we introduced an energy level diagram that accounts for the thermodynamic of the anthocyanin system in acidic medium (Pina et al. 1997; Pina 2014a). This diagram can be straightforwardly constructed provided that the equilibrium constants, eq. (1) to eq. (4), of the system have been determined, see Scheme 1.2.
Scheme 1.2 Energy level diagram for anthocyanins and related compounds in acidic medium.
Source: Adapted from Pina 2014a. © 2014 John Wiley & Sons.
1.3 Extending the Multistate of Anthocyanins and Related Compounds to the Basic Region
In many flavylium derivatives from natural or synthetic origin, including anthocyanins, it is indispensable to extend the multistate study to basic medium.
In
