Quantum Mechanical Insights into Biological Processes at the Electronic Level - Computational Modeling of Biological Systems - page 135

Fig. 2 Hydrolysis of urea catalyzed by urease, starting from the initial complex with bidentate
coordination of urea to the active site. Adapted with permission from [ 16 ]
a proton can bind to the di-iron site of RNR and facilitate changes that affect the
electronic structure of the iron sites and activate the site for further reaction. Two
potential reaction pathways were presented: one where water adds to Fe1 of the
cis --1,2 peroxo intermediate P causing opening of a bridging carboxylate to form
intermediate P 0 that has an increased electron affinity and is activated for proton-
coupled electron transfer to form the Fe(III)Fe(IV) intermediate X; and the other
that is more energetically favorable where the P to P 0 conversion involves addition
of a proton to a terminal carboxylate ligand in the site which increases the electron
affinity and triggers electron transfer to form X (Fig. 4 ). Both pathways provide a
mechanism for the activation of peroxy intermediates in binuclear nonheme iron
enzymes for reactivity.
One may argue against the use of UDFT for calculations on enzymes such as
ureases and ribonucleotide reductases. For example, Ni 2 C is a metal cation with the
ŒAr4s 2 d 6 electronic configuration. The incomplete population of the d-set of AOs
leads to an ambiguity in the number of unpaired electrons on each Ni center. This
number depends on the splitting of d-AO in a particular coordination environment
of Ni. Several electronic states may lie close in energy, and may change order even
in the course of the catalyzed reaction. Hence, the nature and number of singly
and doubly occupied d-AOs on Ni may change. In addition, when two Ni centers