With the huge interest in click chemistry for in vivo applications--the staudinger ligation and the Huisgen cycloaddition, I was wondering, just how viable are these reactions in real world settings? Assuming second order kinetics, the fastest ever reported Staudinger ligation click reaction had a rate constant of 7.7x10^-3 M-1s-1 and the fastest ever Huisgen click reaction has kinetic rate constant of 2.3 M-1s-1. In other words, at concentrations of 1uM (which is near physiological concentration ranges of drugs etc), for a rxn time of 1h, and assuming that we get complete conversion and no side products, that those reactions will produce yields of 0.003% and 0.8% respectively. The kinetic barrier reported seems like a huge obstacle to me. For comparison's sake, enzymes that bioconjugate work with rate constants on the order of 2.7 x 10^6 M-s-1. So really, how viable is the click chemistry approach for in vivo application? Are we primed for failure?