Computational Studies on Structural, Excitation, and Charge-Transfer Properties of Ureidopeptidomimetics

Abstract

Peptides with ureido group enclosing backbones are considered peptidomimetics and are known for their higher stabilities, biocompatibilities, antibiotic, inhibitor, and charge-transduction activities. These peptidomimetics have some unique applications, which are quite different from those of natural peptides. Hence, it is imperative to appreciate their properties at a microscopic level. In this regard, this work outlines, in detail, the charge transfer (CT) properties, holemigration dynamics, and electronic structures of various experimentally comprehended ureidopeptidomimetic models using density functional theory (DFT). Time-dependent DFT and complete active space self-consistent field computations on basic models provide the necessary evidence for the viability of CT from the end enfolding the ureido group to the other end with a carboxylate entity. This donor-to-acceptor CT has been reflected in excitation studies, in which the higher intensity band corresponds to CT from the π orbital of the ureido group to the π* orbital of the carboxylate entity. Further, hole-migration studies have shown that charge can evolve from the ureido end, whereas the hole generated at the carboxylate end does not migrate. However, hole migration has been reported to occur from both ends (amino and carboxylate ends) in glycine oligopeptides, and our studies show that the ability to transfer and migrate charge can be tuned by modifying the donor and acceptor functional groups in both the neutral and cationic charge states. We have analyzed the possibility of hole migration following ionization using DFT-based wave-packet propagation and found its occurrence on a ∼2−5 fs time scale, which reflects the charge-transduction ability of peptidomimetics.

Density functional theoretical studies on photoswitching and charge migration dynamics of thio and selenoureidopeptides

“…Presence of H‐bond between H (28) and O (14) in M3 and M4 models induces the formation of a 6‐membered pseudocycle at the carboxylate end. The trend remains the same in case of excited‐state geometries. The longer chain models (M3S, M3Se, M4S, M4Se along with M2S) prefer linear geometry at the ground state, which is contradictory to that reported for similar longer chain UPs . The increase in chain length (M3 and M4) does not give way for folded conformers, hence both the models prefer linear geometry because it is the lowest energy conformer.…”

“…And note that this kind of a rotation of peptide bond is not observed for UP models . The gradual change from delocalized “n” orbital to localized ones on going down the chalcogen group could be the reason (Figure S4).…”

“…The VI creates a localized hole in the highest occupied molecular orbital (HOMO) by removing the electron from the same. The details of the methods have been illustrated by Remacle et al and used already for similar molecules …”

“…Generally, peptides that contain sulphur and selenium are prone to display interesting physical, chemical and biological activities owing to its less electronegativity when compared to regular peptides . The same is expected in the case of UP derivatives . However their (UP, TUP, and SUP) applications have not been explored to a greater extent because of the complexity in their synthesis .…”

DFT Studies on the Molecular Structure, Regioisomerism, Ground and Excited state Charge Transfer Properties of Spiro‐heterocycles

“…After the sudden ionization of a molecule, the positive charge or the hole produced can migrate throughout the system on a femtosecond timescale [18] . This phenomenon has been previously explored theoretically in different biomolecules like peptides, molecular clusters, ionic liquids, water‐dimer [18] . Experimentally, hole transport has been reported through perovskite solar cells which use a spiro framework to connect the donor‐acceptor moieties [19] .…”