Cycloaddition of Strained Cyclic Alkenes and Ortho-Quinones: A Distortion/Interaction Analysis

Abstract

The chemistry of strained unsaturated cyclic compounds has experienced remarkable growth in recent years via the development of metal–free click reactions. Among these reactions, the cycloaddition of cyclopropenes and their analogues to ortho -quinones has been established as a highly promising click reaction. The present work investigates the mechanism involved in the cycloaddition of strained dienes to ortho -quinones and structural factors that would influence this reaction. For this purpose, we use B97D density functional theory calculations throughout, and for relevant cases, we use spin component–scaled MP2 calculations and single–point domain-based local pair natural orbital coupled cluster (DLPNO-CCSD(T)) calculations. The outcomes are analyzed in detail using the distortion/interaction model, and suggestions for future experimental work are made.

Evaluation of Dibenzocyclooctyne and Bicyclononyne Click Reaction on Azido‐Functionalized Antifouling Polymer Brushes via Microspotting

“…[ 9,10 ] A successful example is benefitting from the activation by ring strain in the structure of reactants, for example, cycloalkyne or cycloalkane. [ 11–15 ] Particularly, the strain‐promoted alkyne‐azide cycloaddition (SPAAC) is an outstanding member of this class owing to its excellent chemical stability, non‐toxic and mild reaction conditions, and high coupling efficiency for bio‐orthogonal conjugations. [ 16–19 ]…”

“…[9,10] A successful example is benefitting from the activation by ring strain in the structure of reactants, for example, cycloalkyne or cycloalkane. [11][12][13][14][15] Particularly, the strain-promoted alkyneazide cycloaddition (SPAAC) is an outstanding member of this class owing to its excellent chemical stability, non-toxic and mild reaction conditions, and high coupling efficiency for bio-orthogonal conjugations. [16][17][18][19] Commonly, azide derivatives are used as bio-tags in biochemistry due to easy integration with biomolecules, for example, in metabolic labeling for living cells with azido functionality, [20,21] post-synthetic modification, [22,23] and in vitro enzymatic transfer.…”

Computational insights into the inverse electron-demand Diels–Alder reaction of norbornenes with 1,2,4,5-tetrazines: norbornene substituents’ effects on the reaction rate

“…In order to get more insights about the chemical reactivity observed between these two cycloalkenes, we used the activation strain model developed by Bickelhaupt and Houk. 27 This theoretical model has been successfully applied to a diverse range of chemical reactions, including nucleophilic substitution, 28 elimination, 29 cycloadditions, 30 oxidative addition, 31 organometallic chemistry, 32 and other processes in organic chemistry. The activation strain model (ASM), also known as the distortion/interaction model, is a systematic development of an energy decomposition of equilibrium structures (reactant complex and product complex), transition states, and nonstationary points along the reaction coordinate (ζ).…”

Role of Protein Damage Inflicted by Dopamine Metabolites in Parkinson’s Disease: Evidence, Tools, and Outlook

“…Further optimization of the LC-MS methodology that comprehensively identifies DA–protein adducts would aid this effort. Harnessing the unique reactivity of ortho -quinones may prove useful in enriching DA–protein adducts in biological samples through cycloadditions with strained cyclic alkenes . In addition, antibodies raised against particular DA-modified proteins are currently lacking and would also be a useful enrichment and detection tool.…”

“…Harnessing the unique reactivity of ortho-quinones may prove useful in enriching DA−protein adducts in biological samples through cycloadditions with strained cyclic alkenes. 227 In addition, antibodies raised against particular DA-modified proteins are currently lacking and would also be a useful enrichment and detection tool. To determine the pathological contribution of various DA-derived metabolites, probes akin to the reported DA yne and 6-OHDA-PEG3-yne could be designed to mimic specific oxidation states of DA metabolites.…”