Computational study on the reactivity of tetrazines toward organometallic reagents.

The possible reaction pathways between methyllithium and disubstituted 1,2,4,5-tetrazines (bearing methyl, methylthio, phenyl, and 3,5-dimethylpyrazolyl groups) were investigated by means of the density functional theory B3LYP/6-31G* method. Solvation was modeled using the supermolecule approach, adding one tetrahydrofuran molecule to the complexes. Comparison of the calculated energies and structures for the alternate azaphilic and nucleophilic addition pathways showed that the azaphilic addition is kinetically favored over nucleophilic addition, while thermodynamically the nucleophilic addition is usually preferred.

Clickable fluorophores for biological labeling--with or without copper.

The synthesis of a set of new clickable fluorophores that virtually cover the whole visible spectrum reaching the near infra-red regime is presented herein. Besides dyes that are capable of participating in classical copper catalyzed 1,3-dipolar cycloaddition reactions with the counterparting function we have also prepared dyes containing a cyclooctyne moiety, an alkyne derivative that enables copper free clicking to azides. The suitability of these dyes for fluorescent labeling of biomolecules is presented by examples on model frameworks representing major biopolymer building blocks.