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Strong bonds are made by the overlap of closely matched orbitals in size and energy.

Bond cleavage sometimes require catalysts. Due to the high bond energy of C-H of 105.0 kcal/mol (439.32 kJ/mol), it requires a lot of energy to cleave the hydrogen atom and bond a different atom to the carbon. Therefore, a mechanism, such as non-directed C–H functionalization can be used, where 2-pyridone ligand and palladium catalyst in silver acetate allow for the C-H bond cleavage.

Ring-opening
In a ring-opening, the cleaved molecule remains as a single unit. For example, an epoxide ring is opened by ionic mechanisms, in which the polar carbon–oxygen bond is cleaved.

Applications
In biology, cleaving agents are used in proteome analysis where proteins are cleaved into smaller peptide fragments. Examples of cleaving agents used are cyanogen bromide, pepsin, and trypsin.