Halogen Bonding: From Fundamentals to Applications

Abstract

Guest Editors Maté Erdélyi, Catharine Esterhuysen, and Weilang Zhu introduce the joint Special Collection on Halogen Bonding published by ChemPlusChem and The Chemical Record. This collection is organized in association with the 4th International Symposium on Halogen Bonding (ISXB4) and features top multidisciplinary contributions where halogen bonding plays a pivotal role, including computational, synthetic and catalytic, supramolecular and crystal engineering, and biological investigations and applications. Despite the first observations of halogen bonding dating back as far as to the early 19th century,1 it received marked interest earliest in the 1950s when Odd Hassel2 reported the first X-ray crystallographic structure of a halogen-bonded complex.3 Following the impactful yet sporadic discoveries of the late 20th century that laid the groundwork for our current understanding, halogen bonding has developed into a distinct and quickly growing research field over the past two decades. The biennial conference series “International Symposium on Halogen Bonding (ISXB)” has become the prime forum for discussions around the developments in the field. The series took off in 2014 in Porto Cesareo (Italy),4 and was continued in Gothenburg (Sweden, 2016)5 and in Greenville (USA, 2018)6 with the latest edition to take place in Stellenbosch (South Africa) in March 2020; however this became an online event in November 2020 as a result of the COVID-19 pandemic. The latter meeting attracted 229 participants, who presented 71 talks (in a mixture of live and pre-recorded formats) and 90 posters that spanned a wide range of topics of both fundamental and applied character. The contributions covered the following themes: Nature of X-bonding Supramolecular chemistry and crystal engineering Solid state properties Understanding X-bonding behavior Applications in synthesis, catalysis and industry Applications in solution chemistry and biology This joint Special Collection of The Chemical Record and ChemPlusChem presents a selection of topics that were discussed at the symposium, giving a flavor of a successful event and reflecting the width of the topics discussed, including computational, synthetic, supramolecular, and biological investigations where halogen bonding plays a pivotal role. The broad, multidisciplinary nature of the field of halogen bonding is reflected in the contributions to the Special Collection, which also follow the themes of the ISXB-4 conference. They also highlight the advantage of holding such a multidisciplinary meeting, as many of the contributions cut across themes, combining theoretical calculations, experimental studies, and/or applications to a wide range of fields. The diversity of the contributions also highlights how far the field has progressed since the first ISXB in 2014. For instance, many of the presentations then focused on the initial electrostatic model based on the σ-hole concept,4 with subsequent meetings showing how this concept has been challenged and gradually refined7 with the increasing awareness of the importance of polarisation and charge transfer. In this Special Collection the nature of X-bonding is further probed through investigating the effects of electronegativity and electrophilicity in halogen, hydrogen (Legon), and tetrel bonding (Saha and co-workers). In the latter study, the even more subtle effect of hybridisation of the C centre in X−C⋅⋅⋅O tetrel bonds is demonstrated. These fundamental studies have deepened our understanding of X-bonding behavior, particularly with respect to how halogen bonds can be modelled (one of the major concerns expressed at the first ISXB4), with this collection including an assessment of radial potential functions for describing halogen bonds (Alkorta and Legon) and an extension of the concept of cooperativity to halogen bonding (Paragi, Fonseca Guerra, and co-workers). As a result, the field has matured to the extent that halogen bonds can be applied to consistently produce supramolecular assemblies through supramolecular chemistry and crystal engineering, such as those of resorcin[4]arenes (Twum, Rissanen, and Beyeh), arylethenynyl helices (Bowling, Speetzen, and Bosch) and fluorous ionic liquids (Cavallo et al.). Such assemblies can then be taken further to study solid state properties, such as in the co-crystals of 1,4-diiodotetrafluorobenzene with 4-biphenylpyridine N-oxide (Wang, Feng, Jin and co-workers), which adaptively capture aromatic guest molecules and hence change their luminescent behavior. Co-crystals of halogen bond donors with molecules with multiple acceptor sites (Aakeröy and co-workers) and the salts of organoiodines and triiodide anions (McMillen, Pennington, and co-workers) are further evidence that halogen bonding in crystal engineering is here to stay. The Special Collection is also further evidence of halogen bonding‘s broad applications in synthesis, catalysis and industry, with halogen bonds being shown to drive anion-binding (Momiyama et al.) and [4+2] cycloaddition (Arai and co-workers) catalysis. Similarly, hydrogen bonding is revealed to be crucial in selenol and thiol oxidation in proteins (Orian and co-workers). Halogen bonding has also found applications in solution chemistry and biology, as seen from the Review on the role of halogen bonding (and other weak interactions) in biology by Shing Ho et al. with our understanding of its scope and limitations, such as how it varies within different solvents (Zeng and co-workers), continuously growing. Research on the halogen bond has led to the insight that the electron density distribution of covalently bonded atoms is anisotropic in general, enabling a range of additional elements to participate in interactions as electrophilic sites. Some of the contributions to this special collection reflect the kinship of halogen bonding with tetrel and hydrogen bonding, for instance. Halogen bonding has become a truly interdisciplinary endeavor that contributes to the development of a continuously growing number of fields. Despite its youthful age, it is not difficult to predict that the rational application of halogen bonding will soon contribute to the development of new and better drugs and improved synthetic procedures, to the establishment of advanced materials, such as halogen-bonded organic frameworks, and will be employed in numerous, so-far unexplored fields. The friendly openness of the halogen bonding community to new approaches and research fields has been an important facilitator of this process, particularly through events such as the ISXB series of conferences, and has provided the basis for the rapid growth of the research field. As the Guest Editors of this Special Collection, we wish to express our gratitude to all our colleagues who contributed to the development of the research field by participating and contributing to the discussion at ISXB-4, and by submitting and/or refereeing manuscripts to this Special Collection. We also thank Jonathan Faiz and Dinesh Talwar, the Editors of ChemPlusChem and The Chemical Record, for their efforts to carry the Special Collection forward. Catharine Esterhuysen: After completing a PhD at the Rand Afrikaans University (South Africa) in 2000, Catharine Esterhuysen joined Stellenbosch University, where she was promoted to professor in 2018. An Alexander von Humboldt fellowship allowed her to join the groups of Gernot Frenking at the Philipps-Universität Marburg in Germany in 2002 and 2010, and Tim Clark at the Friedrich-Alexander-Universität Erlangen-Nürnberg in 2016. She combines her knowledge of computational chemistry and crystallography to explain unusual interactions and their role in the properties of materials. Weiliang Zhu obtained his PhD (1998) from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences. After working as a visiting lecturer and lecturer at Singapore Polytechnic (1998–2004), he moved to the Shanghai Institute of Materia Medica (2004) as a professor and principal investigator, and as Director of the Drug Discovery and Design Center from 2009. His current research interests are focused on molecular modeling, drug design, medicinal chemistry and natural product. Máté Erdélyi graduated from Semmelweis University, and obtained PhD in organic chemistry at Uppsala University. Following postdoctoral research in physical organic chemistry at the University of California, San Diego, in NMR spectroscopy and structural biology at the Max Planck Institute for Biophysical Chemistry, he initiated his independent research at the University of Gothenburg. In 2017, he moved to Uppsala University, and is currently Chair of Organic Chemistry. His research interests encompass halogen bonding, NMR method development, natural product, and medicinal chemistry.

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