|
Physical parameters
|
| Energy required |
They are thermodynamically driven reactions and require energy of more than 20 kcal mol−1, provided that metal is not used as a catalyst |
Very little amount of external energy is required which can be provided by the human cells |
107 and 108
|
| Reaction time |
Reaction completes within a few hours, giving the desired products |
Bio-orthogonal reactions are designed to be rapid |
59
|
| Solvent used |
The reaction can proceed in a variety of solvents such as organic solvents including DMF, THF, aqueous solvents, buffer systems, etc.
|
Acetonitrile or its mixture with phosphate-buffered saline was used by Bertozzi et al. However, recent reports have also demonstrated the completion of the reaction in human plasma, thereby further testifying the bio-orthogonality of this approach |
88 and 109
|
| Kinetics |
Metal-catalyzed click reactions are much faster when compared with the metal-free bio-orthogonal click reactions |
Metal-free bio-orthogonal click reactions exhibit varied kinetics depending on the methodology, e.g., IEDDA possess rapid reaction rate, whereas SPAAC has a slow reaction rate, although structure-modified cyclooctynes such aliphatic and (di)benzoannulated cyclooctynes can accelerate the process |
110 and 111
|
| Order of reaction |
Second |
Second |
112
|
| |
|
Chemical parameters
|
| Catalyst used |
Metals such as copper, ruthenium, etc. enhance the rate of reaction |
As the reactions occur under physiological conditions, the use of metal catalysts is omitted and self-catalyzing parameters like ring strain act as the catalyst in these reactions |
113 and 114
|