Electrostatic Repulsion Controls Efficiency of Cu‐Free Click‐Reaction with Azide‐Modified Semiconductor Quantum Dots

Abstract Determination of factors influencing the efficiency of conjugation of various molecules with colloidal semiconductor quantum dots (QDs) is an important step toward their biomedical application. We have utilized controlled strain promoted [3+2] azid‐alkyne cycloaddition (SPAAC) as an instrument for studying the influence of charge interaction between QDs and molecules on the efficiency of their conjugation. Azide‐modified polymer‐encapsulated core‐shell CdSe/ZnS QDs, bicyclononyne(BCN)‐modified JOE dye and BCN‐BHQ1(Black Hole Quencher 1)‐modified oligonucleotide duplex were used as model objects for conjugation. Strong surface negative charge of carboxylic QDs was shown to suppress efficient conjugation with negatively charged dsDNA or JOE dye (2′,7′‐dimethoxy‐4′,5′‐dichloro‐fluorescein) molecules. Utilization of zwitter‐ionic QDs with reduced surface charge allows significantly enhance the efficiency of QDs conjugation with dsDNA.