Current Organic Chemistry - Volume 10, Issue 7, 2006

This issue is about theoretical organic chemistry, a versatile discipline that has contributed considerably to the understanding of how organic molecules react. It is our greatest pleasure to share with the readers the wonderful reviews by some of the eminent scientists in this field. The interesting chemistry of rare-gas containing organic molecules is reviewed by Prof. McDowell from University of Cambridge, England. The recent advances about the theory of substituent effects are reviewed by Prof. Exner and Prof. Böhm from Czech Republic. Prof. Mo from Western Michigan University of USA has reviewed the orbital deletion procedure and its application to intramolecular electron transfer of organic compounds. Prof. Tsuzuki and co-workers from National Institute of Advanced Industrial Science and Technology of Japan have reviewed the advances about the intermolecular interactions ( π/ π, OH/π , NH/π and cation/π interactions) of aromatic molecules. Prof. Alkorta and co-workers from Instituto de Química Médica at Madrid have reviewed the theoretical studies on chiral discrimination. The exciting chemistry of supramolecular structures such as rotaxanes is reviewed by Prof. Jaime and co-workers from Universitat Autònoma de Barcelona. Prof. Castro and co-workers from Argentina have reviewed the molecular modeling studies of cyclodextrin complexes. Finally, Prof. Sordo and co-workers from Spain have reviewed the theoretical studies on ring opening chemistry of β-lactams in solution and in enzymatic media.

This review summarizes a literature survey on chiral recognition as viewed from a theoretical point. Nevertheless, experimental results in the gas-phase are reported when they are relevant for the theoretical calculations. The review is divided into the following sections: general considerations, experiment vs. theory; pure theoretical results; solvent effects; metals as glue; optical rotatory power, and conclusions.

This review deals with the panorama of current theoretical methods applied to study chemical and physical chemistry properties of cyclodextrins and their inclusion complexes. This study covers from 1998 to the present, with the exception of some papers not included in a rather recent review.

Supramolecular structures are formed by holding two or more molecules without covalent bonds. Although rotaxanes are not supramolecular species but real molecules, the interactions existing between the fragments composing rotaxanes are of the same type of those in supramolecular species. Rotaxanes and cyclodextrins are the two structures being considered in this review. The contribution of the authors in the study of these two classes of compounds by computational techniques will be presented. Aspects like geometry of the complex (bimodality), estimation of association constants, conformational changes produced by the complexation, enantiodifferentiation, changes in the molecular reactivity, formation of aggregates, shuttling of the rotaxanes, and the energetic aspects and the geometry of cyclodiastereomeric rotaxanes are also discussed.

Intermolecular interactions of aromatic molecules ( π/π , OH/π , NH/π and cation/π interactions) are important in many fields of chemistry and biology. These interactions are important for crystal structures, stability of biological systems and their molecular recognition processes. Detailed information on the interactions of aromatic molecules is essential for improved material and drug design. However it is not an easy task to study the magnitude and physical origin of these interactions by experimental measurements only. Recent developments of computational methodologies and increasing computer performance enable us to study these interactions quatitatively by high-level ab initio molecular orbital calculations. High-level ab initio calculations are rapidly increasing our knowledge on the intermolecular interactions of aromatic molecules. This review attempts to introduce methodologies for studying weak intermolecular interactions by ab initio calculations and to summarize recent progress in quantitative analysis of intermolecular interactions of aromatic molecules.

The review reports recent progress in the studies of substituent effects in isolated molecules, i. e. based either on the experimental gas-phase acidities (basicities), or on quantum chemical calculations. Attention was focused on cases when the results differed from or exceeded the traditional views: redefinition of the inductive effect, quantitative estimation of resonance, validity of the Hammett equation, interpretation of the ortho effect, additivity of the enthalpies of formation, acidity of carboxylic acids.

The elucidation of the molecular structure-property relationships requires the rational estimation of steric and electronic effects which govern the molecular structures. To this end, we proposed a simple ab initio method called orbital deletion procedure (ODP) which can quantitatively probe the intramolecular electron transfer effect in carbocations and boranes. This method can not only explore the impact of electron transfer on molecular structures and stabilities, but probe the electron transfer efficiency in some electron donor-bridge-electron acceptor (DBA) complexes. In this Review, we will demonstrate the significance of the intramolecular steric effect by comparing the planar and staggered structures of tetrahydrodiboron (B2H4) and halogenated diboranes (B2X4, X = F, Cl, Br). By deactivating the electronic effect, we found that in these systems the staggered structures are consistently stabilized by 4-11 kcal/mol compared with the planar structures, which supports our very recent conclusion that the ethane rotation barrier is dominated by the steric hindrance rather than the hyperconjugative interactions. We further analyzed a few carbocations and demonstrated how conjugation or hyperconjugation can remarkably influence the molecular structures and properties. Based on the ODP method, we proposed a two-state model which can straightforwardly compute the electron-transfer matrix element which is directly related to the electron transfer efficiency and kinetics in H2C-bridge-CH2 + DBA complexes. We employed this ODPbased two-state model to investigate the electron transport across strain-free linear alkyl chains (CH2)n (n=1-8) and linear π-conjugated bridges (CH=CH)n (n=1-5).

The main focus of this review is a new class of neutral molecules containing chemically bonded rare gas atoms. These compounds are given by the general formula HRgX, where Rg denotes a rare gas atom and X denotes an atom or group of atoms having high electron affinity. They are usually produced by photolysis of a HX precursor in low temperature rare-gas matrices. These novel compounds are highly polar and form weakly bound metastable complexes with other molecules via non-covalent interactions. In this review, we discuss theoretical studies of the structure, bonding, properties and factors influencing the energetic stability of these rare-gas species, the preparation and vibrational spectroscopy of these molecules and some theoretical approaches to understanding the nature of these molecules, with experimental studies discussed where appropriate. The complexes formed by the rare-gas compounds exhibit unusual structural and spectroscopic features, which are also discussed in the review.

Herein we present an overview of the theoretical studies on the cleavage of the β-lactam C-N bond in aqueous solution and in enzymatic media. We discuss first the alkaline hydrolysis of β-lactams that has been investigated thoroughly by means of semiempirical, ab initio, and density functional calculations, while solvent effects have been typically included using a discrete and/or continuum representation of solvent. These computational studies investigate the origin of the energy barrier, the structure and stability of tetrahedral intermediates, substituent effects, catalysis by transition metals such as Zn(II) and Cu(II), etc. Other recent articles have been devoted to the analysis of the acidic and neutral hydrolysis/alcoholysis of β-lactams as well as their ozonolysis. We also review a series of theoretical studies that describe the ammonolysis/aminolysis of monocyclic and bicyclic β-lactams using density functional calculations combined with a solvent continuum model. The aminolysis reaction between the lysine 199 residue of Human Serum Albumin and benzylpenicillin is also revised. The second part of this review concentrates on the β-lactam ring opening catalyzed by the "penicillin recognizing proteins" family of bacterial enzymes, which includes both serine-proteases and zinc-proteases. For the serine proteases ( β-lactamases and penicillin binding proteins), quantum chemical optimizations on cluster models of their active sites and hybrid quantum chemical and molecular mechanical calculations on the whole enzymes, have been applied to examine several competing mechanisms that differ in the identity of the required base to activate the nucleophilic serine. For the zinc- β-lactamases, the gross of computational work has been aimed at examining the coordination chemistry of the catalytic metal centers, and only a few mechanistic studies have been reported to date.