Different Environment Simulation Of The Peptide Unit Proton Transfer Mechanism In Theoretical Research,

The peptide plays a vital role in biological systems, and the tautomerization of the peptide unit is important for the determination of structures and functions of biological molecules. Proton transfer (PT) or proton exchange taking place universally in peptides may be related with some important functions in living systems, e.g., enzymatic catalysis, fragmentation processes, and information transfer, etc., which can be illustrated by the relevant investigations recently. Thus, it is no wonder that the explorations of the PT in modeling peptide units (MPU) have become a prime importance area in chemistry and biology. Investigations on proton transfer isomerization of the modeling peptide units under different biological surroundings should be helpful for the understanding of proton transfer phenomenon in the peptide bond. A series of work have been carried out employing the hybrid density functional theory B3LYP/6-311+G^* and B3LYP/6-311++G^** methods in this thesis. The primary innovations are related as follows.Firstly, the neighboring group effects on proton transfer isomerization in modeling peptide unit and the water-assisting role have been studied for the implication of peptide bond isomerizations under different biological surroundings. Analyses indicate that water adduction with the modeling peptide unit play a stabilization role to the system. Moreover, the isomerization reactions for direct and water-assisted proton transfers are endothermic processes. Similar to the effect of water assistance, the reaction energy is decreased when strong electron-donating group is linked to the modeling peptide unit. The activation barriers for the proton transfer isomerizations of these systems go down when water molecules mediate the proton transfers. Moreover, the introduction of an electron-donating group into the Rl or R2 sites of the modeling peptide unit may promote proton transfer process.Secondly, the influence of the amino acid residues on the proton transfer inthe formamide and the derivatives, the peptide bond unit analogues, have been investigated systematically to explore their active roles in assisting proton transfers occurring widely biologically. Analyses indicate that the assisting role of amino acid residues in the eight-membered ring patterns is more effective than that in the six-membered ring patterns. More important is that the greater the capability of the assisting group for donor proton, the lower the activation energy for the double proton transfer. Well then, acetic acid is the most efficient amino acid residue side-chain in assisting PT processes of the peptide bond. Especially, the double proton transfer process proceeds with a stepwise mechanism via an eight-membered ring structure when methylguanidine servers as the assisting group. At the same time, it can proceed with a concerted asynchronous mechanism through the formation of a six-membered ring structure, which is also true when methylamine acts as an assisting group. However, concerted synchronous mechanism has been observed in the other dimmers formed by modeling peptide unit with amino acid residues.In the end, the effects of metal cation on the proton activity in the peptide unit have been investigated. Here, theoretical study of the calcium's effect on the proton countertransport of the peptide unit when calcium pump is formed has been carried out. Analyses of NBCK NMR, acidity as well as assisting dissociation parameters indicate that ionization states of the acidic residues forming the Ca2+-binding sites may influence the activity of the amide H in MPU and transport proton H of the peptide in the direction opposite to Ca2+. Moreover, calculated results show that the variations of the parameters discussed for amide H of MPU get smaller when the acidity of Ca2+ ion decreases.