Synthesis of 1,2‐Dioxetanes as Thermochemiluminescent Labels for Ultrasensitive Bioassays: Rational Prediction of Olefin Photooxygenation Outcome by Using a Chemometric Approach

Abstract

Great interest in new thermochemiluminescent (TCL) molecules, for example, in bioanalytical assays, has prompted the design and synthesis of a small library of more than 30 olefins to be subjected to photooxygenation, with the aim of obtaining new 1,2-dioxetane-based TCL labels with optimized properties. Fluorine atoms on the acridan system remarkably stabilize 1,2-dioxetanes when they are located in the 3- and/or 6-position (4 h and 4 i). On the other hand, 2,7-difluorinated acridan dioxetane (4 j) showed a significantly enhanced fluorescence quantum yield with respect to the unsubstituted dioxetane (4 a). Some of the synthesized olefins did not undergo singlet oxygen addition and a rationale was sought to ease the photooxygenation step, leading to the TCL dioxetanes. A chemometric approach has been adopted to exploit principal component analysis and linear discriminant analysis of the structural and electronic molecular descriptors obtained by DFT optimizations of olefins 3. This approach allows the steric and electronic parameters that govern dioxetane formation to be revealed.

Thermochemiluminescent semiconducting polymer dots as sensitive nanoprobes for reagentless immunoassay

“…We found that the lnA and Ea activation parameters of 1,2-dioxetane 1 in CN-PPV Pdots were 21.1 ± 2.4 kcal mol −1 K −1 and 21.4 ± 3.1 respectively. Such values were significantly lower than the values measured for the 1,2-dioxetane 1 in the solid state, 27 as already found for compound 1 entrapped in silica NPs. However, the thermal decomposition reaction in silica NPs was much faster than that in Pdots.…”

“…Substrate 1 was synthesized following a previously reported procedure (for more details see Supporting Information). 27 The 1,2-dioxetane 1 -doped Pdots were prepared following a co-nanoprecipitation method. 43 In a typical procedure, stock solutions of CN-PPV (1 mg/mL), PS-COOH (1 mg/mL) and substrate 1 (2 mg/mL) in THF were prepared.…”

“…24,25 In addition, by modifying the molecular structure of the 1,2-dioxetane derivative it will be possible to finely tune the TCL properties in terms of TCL quantum yield, emission wavelength and decomposition temperature. 26,27 A quite low triggering temperature ( e.g. around 100°C) will avoid the use of expensive heat-resistant tubing and materials, also considering that the biosensing part of the device will be disposable, thus it will not sustain several heating cycles.…”

Thermochemiluminescent peroxide crystals

“…If these chemiluminophores are chemically modified to be stable at room temperature, their decomposition can be induced by heating or by application of mechanical force, and the respective phenomena are referred to as thermo- and mechanochemiluminescence. It was demonstrated recently that mechanochemiluminescent polymers can be prepared by incorporating mechanoluminophores in their polymer backbone 5,6 , and thermochemiluminescence was also accomplished by heating of deposited nanoparticles 7–9 and microcrystalline powder 10 . Chemiluminescence in the pure macroscopic solid state, however, was deemed unfeasible due to the very limited ability of molecules for diffusion required for their reaction and the anticipated low quantum yields.…”

The Dibenzosuberenone Scaffold as a Privileged Substructure: From Synthesis to Application

“…Therefore, the Quintavalla and Lombardo group synthesized a small library of more than 30 alkenes to be subjected to photooxygenation, with the aim of obtaining new 1,2-dioxetane-based TCL labels with optimized properties. 115 Furthermore, to verify the capability of the lithium diisopropylamide (LDA) model to predict the reactivity of new compounds with singlet oxygen, the fluorenylalkene 171 (central five-membered ring) and the new alkene 173 (central seven-membered ring) were prepared (Scheme 28). The fluorenyl-derived alkene 171 was predicted to be reactive with a raw canonical score of 30.8 due to an almost completely planar arrangement of the aro-matic rings with respect to the plane defined by the C=C bond (ϕ 1 , ϕ 2 = 159.8°), whereas 5-dibenzosuberenone-derived alkene 173 was predicted to be unreactive with a raw canonical score of -39.9 due to its significantly smaller dihedral angles ϕ 1 and ϕ 2 (113.3°).…”