Theoretical Study of the Thermolysis Reaction and Chemiexcitation of Coelenterazine Dioxetanes

Abstract

Coelenterazine and other imidazopyrazinones are important bioluminescent substrates widespread in marine species and can be found in eight phyla of luminescent organisms. Light emission from these systems is caused by the formation and subsequent thermolysis of a dioxetanone intermediate, whose decomposition allows for efficient chemiexcitation to singlet excited states. Interestingly, some studies have also reported the involvement of unexpected dioxetane intermediates in the chemiand bioluminescent reactions of Coelenterazine, albeit with little information on the underlying mechanisms of these new species. Herein, we have employed a theoretical approach based on density functional theory to study for the first time the thermolysis reaction and chemiexcitation profile of two Coelenterazine dioxetanes. We have found that the thermolysis reactions of these species are feasible but with relevant energetic differences. More importantly, we found that the singlet chemiexcitation profiles of these dioxetanes are significantly less efficient than the corresponding dioxetanones. Furthermore, we identified triplet chemiexcitation pathways for the Coelenterazine dioxetanes. Given this, the chemiexcitation of these dioxetanes should lead only to minimal luminescence. Thus, our theoretical investigation of these systems indicates that the thermolysis of these dioxetanes should only provide "dark" pathways for the formation of nonluminescent degradation products of the chemi-and bioluminescent reactions of Coelenterazine and other imidazopyrazinones.

Conical Intersection in Chemiluminescence of Cyclic Peroxides

“…According to the S 0 and S 1 PECs and their energy gaps calculated by LR-TDDFT, the authors concluded that the uncatalyzed decomposition of neutral 1,2-dioxetanone leads the S 1 -state product to be more efficient than the ET-catalyzed decomposition of the anionic ones. The main evidence to support this conclusion is that a “large and flat biradical region of degeneracy” was observed in neutral decomposition but was absence in anionic decomposition. These explanations regarding the chemiexcitation were incorrect and misunderstood the CI and chemiexcitation.…”

“…Although the existence and roles of S 0 /S 1 CIs in CL of cyclic peroxides were identified and characterized in some theoretical calculations, there are still some misunderstandings in many theoretical works − regarding the chemiexcitation mechanism of cyclic peroxides. In these theoretical studies − by DFT and LR-TDDFT, the authors did not calculate the Φ S but simply estimated it by a unique criterionthe “degenerated S 0 and S 1 state” or “S 0 /S 1 energy gaps”.…”

“…Although the existence and roles of S 0 /S 1 CIs in CL of cyclic peroxides were identified and characterized in some theoretical calculations, there are still some misunderstandings in many theoretical works − regarding the chemiexcitation mechanism of cyclic peroxides. In these theoretical studies − by DFT and LR-TDDFT, the authors did not calculate the Φ S but simply estimated it by a unique criterionthe “degenerated S 0 and S 1 state” or “S 0 /S 1 energy gaps”. According to the S 0 and S 1 PECs and their energy gaps calculated by LR-TDDFT, the authors concluded that the uncatalyzed decomposition of neutral 1,2-dioxetanone leads the S 1 -state product to be more efficient than the ET-catalyzed decomposition of the anionic ones.…”

Combined Experimental and Theoretical Investigation into the Photophysical Properties of Halogenated Coelenteramide Analogs

“…BL is widespread in nature and can be found in organisms as different as fireflies, jellyfishes, bacteria, and fungi, among others [1][2][3][4]. Typically, light emission from CL/BL reactions originates due to the formation of a high-energy peroxide intermediate, which decomposes rather quickly with high exothermicity, which allows for chemiexcitation to excited states [5][6][7][8][9][10].…”

Dissociation Time, Quantum Yield, and Dynamic Reaction Pathways in the Thermolysis of trans-3,4-Dimethyl-1,2-dioxetane

“…The thermolysis of the four-membered heterocyclic peroxides, e.g., 1,2-dioxetane, generates electronically excited state carbonyl compounds that emit light to release the excess energy (see Figure ). The enhancement of the quantum yields of singlet and triplet chemiexcitation was achieved experimentally by the methylation of the 1,2-dioxetanes. , The chemiluminescent mechanism has been studied by computing potential energy surface (PESs), locating minima, transition states (TSs), and conical interactions and/or intersystem crossings, and identifying the potential reaction pathways. − The dynamical quantities, e.g., dissociation time and branching ratios, however, cannot be analyzed in the context of critical points and PESs. The high demand for the nonadiabatic molecular dynamics (NAMD) methods, in which the nuclear motion is regulated by multiple electronic states, has led to the development of different approaches. − As the full quantum-mechanical methods are expensive and limited to a few degrees of freedom, − the trajectory surface hopping (TSH) method has emerged as one of the most popular tools for the NAMD simulations, which was used recently to study the chemiluminescent processes for the four-membered heterocyclic peroxides …”