Editorial [Hot topic: Electron Transfer, Hydrogen and Peptide Bonds (Guest Editor: Petar M. Mitrasinovic)]

Long range electron transfer plays an important role in determining the three-dimensional structures adopted by extended molecular systems such as proteins, nucleic acids, organic-metal complexes, etc. The resulting attraction, which is conceivable as a chemical association of two or more molecules or of different parts of one very large molecule, provides a stabilizing force for the overall donor-acceptor complex. The nature of the attraction is not a stable chemical bond and is much weaker than covalent forces, and it is thus better characterized as a weak electron resonance. In this thematic issue of Current Organic Chemistry, eminent experts have reviewed recent advances in our understanding of these ubiquitous processes by posing more attention to the structure-function relationships. To better understand the mechanistic aspects of charge transfer reactions, the discrete state approach to electron transfer rates is not only a fully justified but an indispensable condition for it. Recent developments in the dynamics of the elementary electron transfer reactions have been reviewed by Peluso with a particular emphasis on the early electron transfer steps in bacterial photosynthetic reaction centers. There are numerous examples in the literature where there is evidence that CH••OH-bonds play important roles in the structure of small molecules and complexes. In this light, Scheiner details means of estimating the energetic contribution of a given CH••OH-bond to protein structure, and how this quantity depends upon the geometry of the interaction, and its relation to experimental measures, such as spectroscopic data. Because of insufficient experimental information on noncovalent interactions such as dispersion, hydrogen-bonding and stacking interactions between biomolecules, sophisticated quantum-chemical calculations have been shown to be an acceptable solution to this problem (Pavlov and Mitrasinovic). Novel methods for the mild and site-specific derivatization of proteins, DNA, RNA, and carbohydrates have been developed for applications such as ligand discovery, disease diagnosis, and high-throughput screening. These powerful methods owe their existence to the discovery of chemoselective reactions that enable bioconjugation under physiological conditions - a tremendous achievement of modern organic chemistry. Recent advances in bioconjugate chemistry have been reviewed in this issue (Kalia and Raines). Special emphasis has been placed on the stability of bioconjugation linkages - an important but often overlooked aspect. It is anticipated that this information will help researchers choose optimal linkages for their applications. Chemically modified biomolecules, which contain non-natural residues, have been recently introduced into a variety of biological systems in order to study the mechanism of enzyme catalysis or to design catalysts with altered substrate specificities. These new findings in combination with data from the literature have been a fundamental ground for Chirkova et al. to propose a comprehensive model for peptide bond synthesis, thus opening a new frontier in synthetic biology. In addition, the longstanding question on whether the peptide anion charge resides primarily on the ionizing nitrogen or is transferred to the carbonyl oxygen to form an imidate has been resolved using amide hydrogen exchange measurements to predict the conformational stability of proteins (Anderson et al.). Since weak interactions determine fine structures of compounds and create high functionalities of materials, Nakanishi and Hayashi have employed the quantum theory of atoms in molecules (QTAIM) to classify and evaluate weak interactions. The same QTAIM approach has been used by Mitrasinovic to propose a general methodology for extrapolating the nature of organic-metal interfacial interactions by both analyzing the topological features of the electron density at the organic/metal bond critical points (BCPs) and correlating the BCP parameters with experimental quantities such as electron affinity and ionization potential. In this way, the interfacial interactions are given physical definitions without invoking non-invariant concepts such as individual orbitals. Since experiments only detect cumulative effects of several cooperative mechanisms taking place at the metal-molecule contacts, contemporary first-principle calculations used in combination with experimental techniques have been demonstrated to lead towards a comprehensive picture of the interfacial electronic structure (Mitrasinovic). I am very grateful towards my dear colleagues, eminent scientists for their acceptance to be a part of this special issue of Current Organic Chemistry by contributing the impressive review articles on the latest relevant developments in the field. I hope that the overall effort will provide inspiration to modern organic chemists to face new interesting challenges of substantial importance with vigor.