Solvent Effect on the Chemiluminescence of Acridinium Thioester: A Computational Study

Abstract

Chemiluminescent labelling, which is one of the promising procedures of modern immunodiagnostics, is increasingly carried out using acridinium derivatives, an oxidant, and an alkaline aqueous environment. However, the efficiency of the chemiluminescence of luminol or acridinium esters is higher in non‐aqueous solvents such as dimethyl sulfoxide or acetonitrile. Therefore, the search for a new environment for the chemiluminescence reaction, especially the one characterized by a higher quantum yield of chemiluminescence, is one of the aims of current research. Using computational methods (DFT and TD DFT with PCM model of solvent), we examined thermodynamic and kinetic data concerning the chemiluminescence and competitive dark pathways. Our results suggest that better characteristics of the chemiluminescence reaction of acridinium thioester are observed in nonpolar solvents, such as methylcyclohexane, n‐hexane and n‐pentane, than in aqueous media used so far. Further experimental verification is necessary to confirm the possible application of proposed nonpolar solvents in chemiluminescent labelling and hence in immunodiagnostics.

What Other Than Acridinium Esters? Computational Search for New Acridinium-Based Chemiluminogens

“…As previous studies have shown [4][5][6][7]36], acridinium derivatives are easily oxidized with hydrogen peroxide in an alkaline environment. These compounds are susceptible to nucleophilic attack on the carbon atom at the 9 position of acridinium moiety.…”

“…Considering our previous studies on the chemiluminescence reaction of acridinium derivatives, e.g., acridinium esters [4,5,7] or acridinium thioesters [6,36], it can be indicated that the type of leaving group is important for the efficiency of the chemiluminescence process. Comparing the energy profiles of the chemiluminescence reaction of acridinium derivatives determined by computational methods [6], it can be seen that the use of a less electronegative atom, that extends the bonds within the leaving group, results in a more efficient transformation of acridinium derivatives into electronically excited products of the CL reaction.…”

“…Former studies on acridinium esters revealed, the type of the leaving group primarily determines the kinetics and chemical stability and-to some extent-the efficiency of the emission [4,5,7,11]. The choice of atoms to replace the oxygen atom in the case of acridinium ester [4,5,7] or sulfur atom in the case of acridinium thioester [6,36] was based on three parameters: (i) the electronegativity according to the Pauling scale of the chemical element (R), (ii) the bond length formed between the leaving group and the luminogenic part of the chemiluminogen (C-R), and (iii) ease of synthesis of chemiluminogens (especially a commercial availability of substrates for synthesis). The list of analyzed parameters is presented in Table 1.…”

“…In the next step, the reaction with hydroxide anion follows, and as a result, an energy-rich cyclic intermediate arises. In the end, the cyclic intermediate decomposes, by which an electronically excited product-the molecule of 10-methyl-9-acridinone [6,7,36,37]-is formed. From the point of view of the mechanism of chemiluminescence reaction and easier formation of electronically excited products, acridinium derivatives may be accordingly modified.…”

“…In this work, we focus on comparing the results of quantum-chemical calculations of new potential chemiluminogens with the same values for acridinium esters used so far in To the best of our knowledge, no detailed studies on chemiluminogens with a similar structure to acridinium esters have been carried out so far. However, considering the promising computational results on acridinium thioesters [6,36], it seems interesting to investigate how the change of the leaving group of acridinium ester (phenyl group) affects the efficiency of the chemiluminescence reaction. In this paper, we present the computational results of our studies on the effect of the type of leaving group on the thermodynamic and kinetic parameters of the chemiluminescence reaction.…”