Exemplary of this are the a-ketoglutarate (aKG)-dependent non-heme iron enzymes , which carry out C-H activation reactions selectively. C-H activation is difficult to achieve synthetically owing to the high C-H bond dissociation energy and its inertness due to low polarity . These non-heme iron enzymes are studied widely and are known to catalyze a variety of reactions such as C-H hydroxylation, halogenation, epoxidation, desaturation, and ring cleavage . These reactions play important roles in several biosynthetic processes such as primary and secondary metabolism in plants , generation of clinically relevant natural products , DNA repair and transcription. Non-heme iron enzymes are also highly selective in nature. For example, non-heme iron halogenases selectively halogenate the substrate even though they also have the potential to carry out hydroxylation. Prior experimental studies supported with computations suggested that substrate positioning and reactivity of the rebound intermediate could explain the observed selectivity. Furthermore, computational studies have rationalized the selectivity of these enzymes through various hypotheses including substrate positioning using spectroscopic indicators derived from hyperfine sublevel correlation (HYSCORE) spectroscopy, isomerization of metal-oxo/hydroxo intermediates, interactions with the second coordination sphere, frontier molecular orbital energetics, and OH trapping either through protonation of hydroxo or bicarbonate formation. A recent computational study further demonstrated that the selectivity of halogenases depends on the nature of the substrate radical, with halogen transfer favored for secondary carbon radicals and hydroxo transfer preferred for tertiary carbon radicals. Besides their selectivity, likely rate-determining aspects of the catalytic cycles of non-heme enzymes including oxygen activation and hydrogen atom transfer (HAT) have also been computationally investigated.