Applied computational chemistry

Israel Fernández a and Fernando P. Cossío b
aDepartamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040, Madrid, Spain. E-mail:
bDepartamento de Química Orgánica I-Kimika Organikoa I Saila, Facultad de Química-Kimika Fakultatea, Universidad del País Vasco–Euskal Herriko Unibertsitatea, and Donostia International Physics Center (DIPC), P. K. 1072, 20080 San Sebastián-Donostia, Spain. E-mail:

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Israel Fernández

Israel Fernández (Madrid, 1977) studied Chemistry at the Universidad Complutense of Madrid (UCM). In 2005, he earned his PhD (with honors) at the UCM under the supervision of Prof. Miguel A. Sierra receiving the Lilly-Young Researcher Award. After that, he joined the Theoretical and Computational Chemistry group of Prof. Gernot Frenking at the Philipps Universität Marburg as a postdoctoral researcher. In 2009, he received the Young-Researcher Award from the Spanish Royal Society of Chemistry and the Julián Sanz del Río award in 2011. At present, I.F. is Profesor Contratado Doctor at the UCM. His current research includes the experimental and computational study of the bonding situations and reaction mechanisms of organic and organometallic compounds.

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Fernando P. Cossío

Fernando P. Cossío studied chemistry at the Universidad de Zaragoza (Spain) and received his PhD in 1986 at the University of the Basque Country (UPV/EHU, Spain, Prof. C. Palomo). After a postdoctoral stay at CNRS (Talence, France, Dr J.-P. Picard), he joined the UPV/EHU as Profesor Titular in 1988 and Catedrático in 2002. In 1994, after a short stay at UCLA in the laboratories of Prof. K. N. Houk, he decided to combine theoretical and experimental organic chemistry to investigate the origins of selectivity in chemical reactions. His research interests include pericyclic reactions, C–C bond-forming reactions, and medicinal chemistry (design and chemical synthesis of inhibitors of integrins and epigenetic enzymes). At present, F.P.C. is the Scientific Director of Ikerbasque, The Basque foundation for science.

Computational Chemistry has, without any doubt, become a powerful tool in chemistry in the last decades. The tremendous development of computer science, which has led to a significant increase in the accuracy and efficiency of numerical calculations and simulations, has boosted the application of Quantum Theory to problems in Chemistry. In this sense, Computational Chemistry methods have nowadays entered into the toolkit of many chemists, including those mainly oriented towards synthesis, in order to understand and predict the chemical phenomena. This situation is in line with the “Applied Theoretical Chemistry” concept proposed by Roald Hoffmann:1To the chemistry community at large, to my fellow scientists, I have tried to teach “applied theoretical chemistry”: a special blend of computations stimulated by experiment and coupled to the construction of general models – frameworks for understanding.

This themed issue is hence focused on the application of computational/theoretical methods to chemical problems of interest to a wide computational and experimental audience. Special emphasis will be made on the interplay between both sides of chemical science, rather than on recent developments in methods and algorithms (following Charles Coulson's famous dictum “give us insight, not numbers”, recently emphasised by Walter Thiel:2The primary aim is not number crunching but understanding chemistry”). Therefore, this themed issue will cover state-of-the-art applications of computational chemistry in different fields of chemistry.

Computational chemistry, for instance, has shed light on many of the details of how cyclobutanes are assembled in nature, in particular, towards the synthesis of terpene natural products. Specific insights and general principles derived from these theoretical studies are described in the review by Hong and Tantillo (DOI: 10.1039/c3cs60452g). In the field of organometallic chemistry, computational methods have enormously contributed to our current understanding of the involved reaction mechanisms. To illustrate recent efforts in this field, Stirling, Nair, Lledós and Ujaque (DOI: 10.1039/c3cs60469a) present a Tutorial Review devoted to mechanistic studies on the Wacker process stressing the long controversy about the key reaction steps. These authors show how ab initio Molecular Dynamics calculations have helped to obtain a novel understanding of the mechanism and kinetics of the Wacker reaction. In a different context, Musaev, Figg and Kaledin (DOI: 10.1039/c3cs60447k) review recent applications of computational chemistry towards the study of the mechanistic features of mono-N-protected amino acid ligand and cesium-halide base in Pd-catalyzed C–H bond functionalization. These studies have revealed the roles of the CsF base in arylation reactions and predict the unprecedented “Cs2–I–F cluster” assisted mechanism for this transformation.

Two different Tutorial Reviews deal with the ability of computational chemistry to understand chemical reactivity and design more efficient transformations. On one hand, Usharani, Lai, Li, Chen, Danovich and Shaik (DOI: 10.1039/c4cs00043a) review the usage of valence bond (VB) diagrams for a better understanding of chemical reactivity in general, and hydrogen atom transfer (HAT) reactivity in particular. On the other hand, Fernández and Bickelhaupt (DOI: 10.1039/c4cs00055b) present and discuss the so-called Activation Strain Model (ASM) of reactivity, a method which has allowed to gain more insight into the physical factors which control how the activation barriers arise in different fundamental processes within organic and organometallic chemistry.

Frenking, Tonner, Klein, Takagi, Shimizu, Krapp, Pandey and Parameswaran (DOI: 10.1039/c4cs00073k) review novel bonding situations of carbon and group 14 elements. In this Review Article, the authors show how these elements can form donor–acceptor divalent compounds that possess two lone pairs. These types of compounds are known as tetrylones (carbones, silylones, germylones, stannylones, and plumbylones) and their properties can be distinguished from those associated with tetrylenes (from carbenes to plumbylenes). The new bonding situation thus characterized by computational methods poses a formidable challenge for the skills of experimental chemists. In a different context, Parthey and Kaupp (DOI: 10.1039/c3cs60481k) describe the characterization of mixed-valence (MV) systems by means of computational methods, thus permitting a better understanding of the experimental data obtained for these important compounds.

Rationalizing the chemical properties of molecules has been a traditional target of computational chemistry. Two totally different and recent approaches to analyse the properties of molecules and their influence on reactivity have been considered in this themed issue. Geerlings, Fias, Boisdenghien and De Proft (DOI: 10.1039/c3cs60456j) describe the nearly unexploited linear response function within the context of conceptual Density Functional Theory. On the other hand, Sparta and Neese (DOI: 10.1039/c4cs00050a) provide a brief overview of the chemical applications carried out by local pair natural orbital coupled-electron pair and coupled-cluster methods. Benchmark tests reveal that these methods reproduce, with excellent accuracy, their canonical counterparts. At the same time, the speed-up achieved by exploiting the locality of the electron correlation has allowed the tackling of chemical systems that, due to their size, would normally only be addressable with density functional theory.

Biomolecules and materials chemistry constitute a challenge for computational chemistry. This themed issue covers these topics with two reviews. In the first one, Viñes, Gomes and Illas (DOI: 10.1039/c3cs60421g) describe the main computational methods to understand the intimate chemistry of metallic nanoparticles (NPs). In this sense, the effects of different parameters such as size, shape and composition are evaluated and compared with available experimental data. This deeper understanding of NPs can eventually permit the design of more active and efficient species. In the second, Orozco (DOI: 10.1039/c3cs60474h) presents the current state-of-the-art theoretical approaches to the study of protein dynamics. These advanced computational techniques are extremely useful to understand and eventually predict the structure and chemical behaviour of these macromolecules, whose importance cannot be overemphasised. In this authoritative review, the most recent advances and examples of use are presented and discussed, as well as the expected lines of development in the near future.

Computational chemistry has also contributed to the chemists' toolkit by providing chemical concepts, which are not experimentally measurable. For instance, aromaticity is an essential concept in chemistry, which was introduced to account for the unusual stability, reactivity, molecular structures, and other properties of many unsaturated organic compounds. This concept has been extended to other systems with mobile electrons. This themed issued includes two reviews on the role of aromaticity in special systems. In a Tutorial Review, Schleyer, Wu, Fernández and Cossío (DOI: 10.1039/c4cs00012a) present the aromaticity of transition structures associated with pericyclic, pseudo-pericyclic and non-pericyclic reactions. These authors discuss how computational chemistry permits to quantify the aromaticity of the corresponding saddle points and distinguish the nature of these cyclization processes. In a more focused Review Article, Garcia-Borràs, Osuna, Luis, Swart and Solà (DOI: 10.1039/c4cs00040d) show how computational chemistry provides models and interpretative tools to understand the aromatic properties and the reactivity of electronically sophisticated systems such as endohedral fullerenes.

We are really grateful to the authors whose outstanding contributions comprise this themed issue. In addition, we wish to thank Prof. Kendall N. Houk for writing his authoritative and inspiring foreword. Finally, we gratefully thank the staff of Chemical Society Reviews for their help in making this ambitious project a reality.


  1. Roald Hoffmann – Biographical,, Nobel Media AB 2013, web 29 Apr 2014,
  2. W. Thiel, Angew. Chem., Int. Ed., 2011, 50, 9216 CrossRef CAS PubMed.

This journal is © The Royal Society of Chemistry 2014