20th Anniversary Blog Series: Luis R. Domingo

2023 marks twenty years of Organic & Biomolecular Chemistry publications. As part of the celebrations, OBC has invited some of the most prominent authors across our history to give their thoughts on the last twenty years of their career alongside their predictions for the next two decades.

Our next entry to the series comes from Professor Luis R. Domingo at the University of Valencia who first published with OBC in 2003, the journal’s first year. He has continued to support the journal with 27 articles across the years, most recently in 2021.

 

About Luis

Luis Domingo wearing a suitLuis R. Domingo obtained his PhD in Organic Chemistry in 1987. In 2010 he attained his current position as a Full Professor at the Department of Organic Chemistry of the University of Valencia. In 2014 he was admitted as a Fellow of the Royal Society of Chemistry. His research interest is the study of organic chemical reactivity by using quantum chemical procedures based on the analysis of the molecular electron density. He has published more than 370 articles and 8 book chapters, being reviewer of more than 690 articles. Today, he has reached an h index of 61, receiving more than 16,450 citations.

In 2009, Domingo proposed the mechanism of polar Diels-Alder reactions against the ‘pericyclic mechanism’, which is followed by many of the experimental reactions and in 2019 he established the relationship between the structure and reactivity of the three-atom-components participating in [3+2] cycloaddition reactions, proposing four different reaction mechanisms. In 2014, he proposed a new model for the C-C bond formation based on the quantum chemical topology of electron density. He emphasised the significance of the global electron density transfer (GEDT) in the activation energies of polar reactions. After the study of relevant organic reactions classified in 1969 as pericyclic reactions, in 2019 the corresponding mechanism was rejected. He has introduced several concepts widely used today as non-concerted two-stage one-step mechanisms, which involve high asynchronous transition state structures, pseudoradical centres, which participate in many organic reactions involving the formation of new C-C single bonds, and the GEDT which discards the arrow curves used in many textbooks to explain the electronic displacement in polar reactions.

In the present century, Domingo and co-workers have developed several reactivity indices within the Conceptual Density Functional Theory, such as the local electrophilicity ωk index in 2002, the empirical nucleophilicity N index in 2008, the reactivity difference index in 2012, and the electrophilic and nucleophilic Parr functions in 2013, commonly used nowadays in the study of polar organic reactions.

After 20 years and more than 250 publications in the field of Theoretical Organic Chemistry, in 2016 Domingo proposed a new reactivity theory named Molecular Electron Density Theory (MEDT), which opposes all theories developed in the past century based on analysis of molecular orbitals such as the Frontier Molecular Orbital (FMO) theory. Domingo’s MEDT proposes the study of organic chemical reactivity based on the analysis of electron density changes during a chemical reaction.

 

First OBC Paper: A. Manuel & L. R. Domingo, Theozyme for antibody aldolases. Characterization of the transition-state analogue, Org. Biomol. Chem., 2003, 1, 637-643, DOI: 10.1039/b209636f

Most recent OBC Paper: M. Ríos-Gutiérrez, P. Pérez, L. R. Domingo & J. Soto-Delgado, The catalytic effects of a thiazolium salt in oxa-Diels-Alder reaction between benzaldehyde and Danishefsky’s diene: A molecular electron density theory study, Org. Biomol. Chem., 2021, 19, 9306-9317, DOI: 10.1039/d1ob01415c

Favourite OBC Paper: L. R. Domingo & J. A. Sáez, Understanding the mechanisms of polar Diels-Alder reactions, Org. Biomol. Chem., 2009, 7, 3576-3583, DOI: 10.1039/b909611f

 

How has your research developed over the last 20 years?

The development at the end of the last century of quantum chemistry tools capable of performing molecular electron density analysis has made significant advances in the field of Theoretical Organic Chemistry during the last 20 years.

After the proposal in 1999 of Parr’s electrophilicity ω index, which provides a quantitative measure of an important reactivity concept in organic chemistry in 2002, the first electrophilicity ω scale of organic molecules able to explain the reactivity of experimental Diels-Alder reactions was presented1. The local electrophilicity ωk index, proposed in 2002, allowed explaining the chemo and regioselectivity in polar cycloaddition reactions2. Later in 2008, the empirical nucleophilicity N index was proposed3,4. Today, the electrophilicity ω and the nucleophilicity N indices allow the quantitative study of polar reactions. Finally, in 2013, the electrophilic and nucleophilic Parr functions were introduced, allowing the understanding of the local reactivity, i.e., the chemo and regioselectivities, in polar reactions5.

After numerous theoretical studies of reaction mechanisms in the period 2002-2014 based on the topological analysis of the molecular electron density, a model for the formation of new C-C single bonds experienced by many organic reactions was proposed in 20146. On the other hand, the recognition of the decisive role of the global electron density transfer (GEDT)6 in the activation energies of polar organic reactions provided a new vision of relevant reactions such as the polar Diels-Alder reactions7, inadequately classified as a pericyclic reaction in 1969.

[3+2] cycloaddition (32CA) reactions are a class of fascinating organic reactions. After 20 years of studying 32CA reactions, an excellent correlation between the electronic structure of the three-atom-components (TACs) and their reactivity was established in 2019. Unlike the 1,2-dipolar structure proposed by Huisgen, four different electronic structures, which experience four different reactivity types, were characterized8. Recent studies have shown that although the electronic structure of the TAC can be modified with substitution, the four types of reactivity can be characterized in most 32CA reactions.

After 20 years of working in the field of Theoretical Organic Chemistry, in 2016, Domingo proposed a new reactivity theory named Molecular Electron Density Theory (MEDT)9, which establishes that changes in electron density along an organic reaction, and not molecular orbital interactions, are responsible for the chemical reactivity of organic molecules.

Many recent MEDT studies of relevant organic reactions have allowed us to reinterpret the organic reactivity based on electron density analysis. A recent study of the four reactions classified in 1969 by Woodward and Hofmann as pericyclic reactions has proved that this mechanism does not exist since the bonding changes in organic reactions are sequential and non-concerted10.

 

How has the field of theoretical organic chemistry changed over the last 2 decades?

The advances carried out in the last 2 decades in the field of theoretical organic chemistry based on the analysis of the molecular electron density, which is the only physical observable, have allowed us to establish new concepts in organic chemistry. This has caused the rejection of models developed in the past such as the FMO theory, the symmetry rules and energy decomposition analyses based on molecular orbitals, all of them proposed in the past century before the possibility to perform any topological analysis of the molecular electron density obtained from Schrödinger’s wavefunction.

On the other hand, the electrophilicity ω and the nucleophilicity N indices, together with the Parr functions have become easy and powerful tools in studying local reactivity in polar reactions for experimental organic chemists.

Finally, the recent topological analysis of the ELF of the reagents in relevant organic reactions such as 32CA reactions has established a good correlation between the electronic structure and chemical reactivity.

 

Where do you see the challenges being for this field over the next 20 years?

The establishment of Schrödinger’s equation in 1926 was one of the more relevant advances in the field of theoretical organic chemistry as it provides the molecular electron density distribution, which determines the structure and reactivity of organic molecules. Still unfortunately, it cannot be resolved even for the simplest organic molecules. In 1932, the molecular orbital theory was established as a mathematical approach to the wavefunction, but inappropriately molecular orbitals were taken as a reality, proposing in 1931 the Hückel’s p-bonds in unsaturated compounds and 1956 Fukui’s FMO theory to explain organic chemical reactivity. Many concepts, such as pericyclic reactions or concerted reactions are still used today in many organic chemistry textbooks.

Extensive work developed in the present century, based on the analysis of the molecular electron density, has allowed the understanding of many organic reactions, rejecting those concepts based on molecular orbital analyses. Unfortunately, there is still strong influence by research groups that continue working with molecular orbital theories to study reaction mechanisms. But in the last two decades, they have not introduced any advances in chemical understanding.

MEDT proposed in 2016, suggests that the analysis of the molecular electron density, which is the only physical observable, is accurate for understanding organic molecules’ electronic structure and reactivity. Today, theoretical and experimental organic chemists have a great variety of quantum chemical tools able to perform a rigorous analysis of the molecular electron density obtained by any computational level, thus rejecting any obsolete molecular orbital analysis. Note that molecular orbitals were defined to approach the wavefunction, the square of which provides the molecular electron density.

The relationship of HOMO and LUMO energies with the ionization potential and the electron affinity used in Conceptual Density Functional Theory to attain the reactivity indices and that between molecular orbital coefficients and the Fukui functions used to study the local reactivity allows explaining the good correlations found between experimental data and FMO analyses, but non HUMO-LUMO interactions, but rather nucleophilic/electrophilic interactions between molecules of different electronegativity are responsible for the chemical reactivity in polar reactions.

These similitudes make it that unfortunately, many people continue using models based on the updated FMO theory, but it is essential to remember that Schrödinger’s wavefunction was proposed only to describe the electron distribution in a molecule and that electronic interactions between particles constituting a molecule, i.e., nuclei and electrons are responsible for electronic energies.

 

Check out the other entries in our blog series here!

 

1. L. R. Domingo, M. J. Aurell, P. Pérez & R. Contreras, Quantitative characterization of the global electrophilicity power of common diene/dienophile pairs in Diels-Alder reactions, Tetrahedron, 2002, 58, 4417-4423, DOI: 10.1016/s0040-4020(02)00410-6 6. L. R. Domingo, A new C-C bond formation model based on the quantum chemical topology of electron density, RSC Adv., 2014, 4, 32415-32428, DOI: 10.1039/c4ra04280h
2. L. R. Domingo, M. J. Aurell, P. Pérez & R. Contreras, Quantitative characterization of the local electrophilicity of organic molecules. Understanding the regioselectivity on Diels-Alder reactions, J. Phys. Chem. A, 2002, 106, 6871-6875, DOI: 10.1021/jp020715j 7. L. R. Domingo & J. A. Sáez, Understanding the mechanism of polar Diels-Alder reactions, Org. Biomol. Chem., 2009, 7, 3576-3584, DOI: 10.1039/b909611f
3. L. R. Domingo, E. Chamorro & P. Pérez, Understanding the reactivity of captodative ethylenes in polar cycloaddition reactions. A theoretical study, J. Org. Chem., 2008, 73, 4615-4624, DOI: 10.1021/jo800572a 8. M. Ríos-Gutiérrez & L. R. Domingo, Unravelling the Mysteries of the [3+2] Cycloaddition Reactions, Eur. J. Org. Chem., 2019, 267-282, DOI: 10.1002/ejoc.201800916
4. L. R. Domingo & P. Pérez, The nucleophilicity N index in organic chemistry, Org. Biomol. Chem., 2011, 9, 7168-7175, DOI: 10.1039/c1ob05856h 9. L. R. Domingo, Molecular electron density theory: A modern view of reactivity in organic chemistry, Molecules, 2016, 21, 1319, DOI: 10.3390/molecules21101319
5. L. R. Domingo, P. Pérez & J. A. Sáez, Understanding the local reactivity in polar organic reactions through electrophilic and nucleophilic Parr functions, RSC Adv., 2013, 3, 1486-1494, DOI: 10.1039/c2ra22886f 10. L. R. Domingo, M. Ríos-Gutiérrez, B. Silvi & P. Pérez, The Mysticism of Pericyclic Reactions: A Contemporary Rationalisation of Organic Reactivity Based on Electron Density Analysis, Eur. J. Org. Chem., 2018, 1107-1120, DOI: 10.1002/ejoc.201701350

 

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20th Anniversary Blog Series: Hirokazu Tamamura

2023 marks twenty years of Organic & Biomolecular Chemistry publications. As part of the celebrations, OBC has invited some of the most prominent authors across our history to give their thoughts on the last twenty years of their career alongside their predictions for the next two decades.

Our first entry to the series comes from Professor Hirokazu Tamamura at the Tokyo Medical and Dental University who first published with OBC in 2003, the journal’s first year. He has continued to support the journal with 12 articles across the years, most recently in 2021.

 

About Hirokazu

Hirokazu Tamamura wearing a suit

Prof Hirokazu Tamamura graduated from the Faculty of Pharmaceutical Sciences, Kyoto University in 1988 (Supervisor: Prof Haruaki Yajima), and received his Ph.D. from Kyoto University in 1995. He became an Assistant Professor of the Faculty of Pharmaceutical Sciences, Kyoto University in 1989 (Boss: Prof Nobutaka Fujii), and then a Lecturer of the Graduate School of Pharmaceutical Sciences, Kyoto University in 1997.

He became a Visiting Fellow at the National Cancer Institute/NIH, USA in 1999-2000 (Lab. Medicinal Chemistry, Boss: Dr Victor E. Marquez) before becoming an Associate Professor of the Graduate School of Pharmaceutical Sciences, Kyoto University in 2005, and then a Full Professor at the Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU) in 2005. His research fields extend to peptide & protein chemistry, chemical biology, medicinal chemistry and organic chemistry.

Hirokazu Tamamura

Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

 

First OBC Paper: H. Tamamura, T. Kato, A. Otaka & N. Fujii, Synthesis of Potent β-Secretase Inhibitors Containing a Hydroxyethylamine Dipeptide Isostere and Their Structure-Activity Relationship Studies, Org. Biomol. Chem., 2003, 1, 2468-2473, DOI: 10.1039/b304842j

Most recent OBC paper: K. Tsuji, T. Ishii, T. Kobayakawa, N. Ohashi, W. Nomura & H. Tamamura, Fluorescence resonance energy transfer-based screening for protein kinase C ligands using 6-methoxynaphthalene-labeled 1,2-diacylglycerol-lactones, Org. Biomol. Chem., 2021, 19, 8264-8271, DOI: 10.1039/d1ob00814e

Favourite OBC paper: H. Tamamura, K. Hiramatsu, M. Mizumoto, S. Ueda, S. Kusano, S. Terakubo, M. Akamatsu, N. Yamamoto, J. O. Trent, Z. Wang, S. C. Peiper, H. Nakashima, A. Otaka & N. Fujii, Enhancement of the T140-based Pharmacophores Leads to the Development of More Potent and Bio-stable CXCR4 Antagonists, Org. Biomol. Chem., 2003, 1, 3663-3669, DOI: 10.1039/b306613b

 

How has your research developed over the last 20 years?

My research has been focused on peptide-based medicinal chemistry over the last 20 years. I started on the development of methodologies for peptide synthesis in 1988 at the Graduate School of Pharmaceutical Sciences, Kyoto University. After receiving my PhD and finishing a postdoctoral fellowship at the National Institutes of Health/National Cancer Institute (NIH/NCI), USA, my research got closer to medicinal chemistry and chemical biology, using peptides and their derivatives. As drug leads for chemotherapy of Alzheimer’s disease, we developed potent beta-secretase inhibitors based on peptide derivatives containing a mimic structure of the enzyme-substrate transition state: a hydroxyethylamine dipeptide isostere. Thus, in 2003, my first paper with OBC on the development of beta-secretase inhibitors was published1. In addition, we had research for the development of antagonists for the chemokine receptor CXCR4, which is correlated with several diseases such as HIV-1/AIDS, cancer and rheumatoid arthritis. Through structure-activity relationship studies on polyphemusin-related peptides, we developed peptidic CXCR4 antagonists, which were designated as T140 derivatives, with high CXCR4-binding affinity, low cytotoxicity and improved biostability. The lead compound, Motixafortide has been progressing through to Phase III clinical studies. In the finding of these CXCR4 antagonists, we published two consecutive papers in 2003 with OBC2,3.

In association with this research, we established a fluorescence-based assay system for CXCR4 binding of compounds using a fluorophore-labeled T140 derivative4. So far we have developed novel CXCR4 antagonists based on nonpeptides as well as cyclic pentapeptide derivatives, which we published in several journals5-10, mostly OBC5,7-10. This target receptor CXCR4 forms dimers in the cell surface because it belongs to the G protein-coupled receptor family. So we developed bivalent CXCR4 ligands with polyproline linkers to catch the dimers in cells11. These bivalent CXCR4 ligands are remarkably more potent than the corresponding monomers. In addition, trivalent CXCR4 ligands highly recognise CXCR4-expressed cells because of accumulation of ligands, which we published with OBC in 201512. The concept of multimerised peptides has been applied to HIV-1 envelope proteins related to membrane fusion, hence dimeric C34 derivatives showed much more potent anti-HIV-1 activity compared to the monomer C34 peptide13.

In my postdoctoral fellowship at NIH/NCI, I had started to develop ligands of protein kinase C (PKC) based on conformationally constrained gamma-lactone derivatives of 1,2-diacylglycerol (DAG). This led to research on the development of DAG-lactones with potent binding affinity for PKC. Initially, we had adopted a competitive assay using radio isotope tritium-labeled phorbol 12,13-dibutyrate to evaluate PKC-binding activity of synthesised DAG-lactones. But from the point of view of environmental health and safety, radio isotope-based screening has been replaced with fluorescene-based screening. Therefore, we developed a fluorescence resonance energy transfer (FRET)-based screening method for PKC ligands, which we published with OBC in 20214. It was an honour that this paper was chosen as the Inside Front Cover of the issue. Taken together my research has focused on medicinal chemistry and chemical biology using peptides, their derivatives and other functional molecules over the last two decades.

How has the field of Medicinal Chemistry changed over the last 2 decades?

Two decades ago, it was common sense that drugs were mostly low molecular weight (small-size) compounds. Through the progress of organic and synthetic chemistry, small-size drugs based on synthesised compounds have been conventionally developed against several diseases. Small molecules have some useful advantages including oral availability and low immunogenicity but serious drawbacks such as low specificity and high possibility of side effects. In this century, high molecular weight biologics (large-size molecules) including human monoclonal antibodies have been developed. Macromolecules have some merits such as high specificity and low possibility of side effects but critical shortages containing low applicability and possible immunogenicity. Accordingly, both small- and large-size drugs have their mutual advantages and drawbacks. In addition, it has been noticed that there is an important drug-like chemical space in the mid-size region between small- and large-size regions. Middle-size molecules, which are categorised between small- and large-size molecules and designated as mid-size drugs, might avoid drawbacks but contain the above advantages possessed by small- and large-size molecules. Therefore, mid-size drugs are ideal as new drug modalities, which encompasses peptides and their derivatives because of their location in this middle-size region.

Small-size drugs can recognise small regions on targeted proteins and usually bind to active centres of enzymes and pockets of receptors. The interface between the drugs and the targeted proteins is relatively narrow. Recently, the number of newly found proteins relevant to several diseases is decreasing since the whole human genome was disclosed in 2003/04. Thus, it has been difficult to find first-in-class drugs (brand-name drugs), which have novel action mechanisms that give new therapeutic approaches to treat diseases. Generic drugs, which can be presented for sale if the patent protection for a brand-name drug expires, or next-in-drugs, which have similar action mechanisms to existing drugs, have come to the forefront as small-size drugs. The concept of molecular target drugs, which bind to only specific molecules relevant to objective diseases and inhibit their functions has come to the fore over the last 20 years. Large-size drugs including human monoclonal antibodies can recognise broad regions on targeted proteins and usually bind to extracellular regions on cell surface receptors. The interface between the drugs and the targeted proteins is relatively expansive. Due to the expansive interface, large-size drugs can specifically recognise targeted proteins and achieve inhibition of protein-protein interaction, hence reducing off-target binding and side effects.

Mid-size drugs containing mostly peptides and their derivatives can have these broad interface regions with targeted proteins, the same as large-size drugs. In addition, mid-size drugs such as peptide derivatives might penetrate cell membranes if the conformation is constrained, therefore can target not only extracellular regions on cell surface receptors but also molecules inside of cells. Accordingly, mid-size drugs can target protein-protein interaction as well as active centres of enzymes and pockets of receptors. They are the current focus for development of next generation drugs. Altogether, the field of medicinal chemistry has been much changed over the last two decades, with medicinal chemists drawing attention to these mid-size drugs.

 

Where do you see the challenges being for the Medicinal Chemistry field over the next 20 years?

I think in the next two decades the field of medicinal chemistry will have been changed even more. In the design of small-size and mid-size drugs, computer calculation and artificial intelligence (AI) will be applied to a greater extent. There are still meaningful targets for small-size drug development, such as the central nervous system along with virus-related diseases including emerging and re-emerging infectious diseases. Currently these drugs are designed based on the structures of the lead compounds complexed with their targeted proteins determined by the X-ray structure analysis and/or NMR analysis accompanied with docking simulations. Recently, cryo-electron microscopy (cyro-EM) has been used for structural analysis with great success. In the future, cryo-EM will be used for more structure analysis and other spectroscopies might be adopted. Even though the practical structures of the lead compounds bound to the targeted proteins sometimes are not discoverable, computer calculation and AI can produce the plausible structures. These techniques are now already useful for the design of potent drugs and will advance more in the future, to much greater levels. Based on bioinformatics, including genome information and chemoinformatics of libraries, AI drug discovery will advance more and more with application of big data of lead compounds and in silico screening. AI and robotics, in which data from each working step can be obtained by the robots’ sensors and then judged by the AI to make progress towards the next steps, will also be developed in the near future.

Peptides and new drug modalities will also become more prominent, especially cyclic peptide derivatives, which possess many advantages as drug candidates. Antibody drug conjugates (ADCs) are ideal compounds, which are conjugates of monoclonal antibodies and small drugs tethered by linkers. In ADCs, the monoclonal antibody can specifically recognise targeted extracellular regions on cell surface receptors while the small drug is then able to reach intracellular target molecules to inhibit their functions. Many ADCs will be developed, mainly for the application for cancer chemotherapy.

An alternative to drugs is chemical protein knockdown. In this strategy, molecules containing ligands of targeted proteins and E3 ligase are synthesised to attack the targeted protein and induce degradation of them by the ubiquitin-proteasome system in vivo, based on specific and non-genetic IAP-dependent protein eraser (SNIPER), proteolysis targeting chimeras (PROTAC) and other similar mechanisms. These molecules can access undruggable targets, which cannot be bound by small size drugs. In the future, I think chemical protein knockdown will be applied to many targets.

Nucleic acid medicine, another drug modality, is now very popular. RNA-dependent polymerease RNA inhibitors and mRNA vaccines have been useful for treatment and prevention of COVID-19 respectively. Thus, these drugs will be expected for the treatment and prevention of new infectious diseases. Research on other gene therapies involving small interfering RNA (siRNA) and antisense nucleotides along with genome editing will become a hot area. Concomitantly, development of vectors for nucleic acid and genome medicine will be actively pursued. In addition, regenerative medicine including cell therapy will make progress in close association with embryonic (ES cells) and induced pluripotent stem cells (iPS cells). Chimeric antigen receptor-therapy (CAR-T) will also be another next generation therapy for cancer. Altogether, I believe various drug modalities will be utilised to have the right drugs for the right targets in the future.

 

Check out the other entries in our blog series here!

 

1. H. Tamamura, T. Kato, A. Otaka & N. Fujii, Synthesis of Potent β-Secretase Inhibitors Containing a Hydroxyethylamine Dipeptide Isostere and Their Structure-Activity Relationship Studies, Org. Biomol. Chem., 2003, 1, 2468-2473, DOI: 10.1039/b304842j 8. H. Tamamura, H. Tsutsumi, H. Masuno, S. Mizokami, K. Hiramatsu, Z. Wang, J. O. Trent, H. Nakashima, N. Yamamoto, S. C. Peiper & N. Fujii, Development of a Linear Type of Low Molecular Weight CXCR4 Antagonists Based on T140 Analogs, Org. Biomol. Chem., 2006, 4, 2354-2357, DOI: 10.1039/b603818b
2. H. Tamamura, K. Hiramatsu, S. Kusano, S. Terakubo, N. Yamamoto, J. O. Trent, Z. Wang, S. C. Peiper, H. Nakashima, A. Otaka & N. Fujii, Synthesis of potent CXCR4 inhibitors possessing low cytotoxicity and improved biostability based on T140 derivatives, Org. Biomol. Chem., 2003, 1, 3656-3662, DOI:10.1039/b306473p 9. T. Tanaka, H. Tsutsumi, W. Nomura, Y. Tanabe, N. Ohashi, A. Esaka, C. Ochiai, J. Sato, K. Itotani, T. Murakami, K. Ohba, N. Yamamoto, N. Fujii & H. Tamamura, Structure-activity Relationship Study of CXCR4 Antagonists Bearing the Cyclic Pentapeptide Scaffold: Identification of the New Pharmacophore, Org. Biomol. Chem., 2008, 6, 4374-4377, DOI: 10.1039/b812029c
3. H. Tamamura, K. Hiramatsu, M. Mizumoto, S. Ueda, S. Kusano, S. Terakubo, M. Akamatsu, N. Yamamoto, J. O. Trent, Z. Wang, S. C. Peiper, H. Nakashima, A. Otaka & N. Fujii, Enhancement of the T140-based Pharmacophores Leads to the Development of More Potent and Bio-stable CXCR4 Antagonists, Org. Biomol. Chem., 2003, 1, 3663-3669, DOI: 10.1039/b306613b 10. T. Tanaka, W. Nomura, T. Narumi, A. Esaka, S. Oishi, N. Ohashi, K. Itotani, B. J. Evans, Z. Wang, S. C. Peiper, N. Fujii & H. Tamamura, Structure-activity Relationship Study on Artificial CXCR4 Ligands Possessing the Cyclic Pentapeptide Scaffold: The Exploration of Amino Acid Residues of Pentapeptides by Substitutions of Several Aromatic Amino Acids, Org. Biomol. Chem., 2009, 7, 3805-3809, DOI: 10.1039/b908286g
4. W. Nomura, Y. Tanabe, H. Tsutsumi, T. Tanaka, K. Ohba, N. Yamamoto & H. Tamamura, Fluorophore Labeling Enables Imaging and Evaluation of Specific CXCR4-Ligand Interaction at the Cell Membrane for Fluorescence-Based Screening, Bioconjugate Chem., 2008, 19, 1917-1920, DOI: 10.1021/bc800216p 11. T. Tanaka, W. Nomura, T. Narumi, A. Masuda & H. Tamamura, Bivalent Ligands of CXCR4 with Rigid Linkers for Elucidation of the Dimerization State in Cells, J. Am. Chem. Soc. (Commun.), 2010, 132, 15899-15901, DOI: 10.1021/ja107447w
5. H. Tamamura, M. Mizumoto, K. Hiramatsu, S. Kusano, S. Terakubo, N. Yamamoto, J. O. Trent, Z. Wang, S. C. Peiper, H. Nakashima, A. Otaka & N. Fujii, Topochemical Exploration of Potent Compounds Using Retro-Enantiomer Libraries of Cyclic Pentapeptides, Org. Biomol. Chem., 2004, 2, 1255-1257, DOI: 10.1039/b401485p 12. W. Nomura, T. Koseki, N. Ohashi, T. Mizuguchi & H. Tamamura, Trivalent Ligands for CXCR4 Bearing Polyproline Linkers Show Specific Recognition for Cells with Increased CXCR4 Expression, Org. Biomol. Chem., 2015, 13, 8734-8739, DOI: 10.1039/c5ob00891c
6. H. Tamamura, K. Hiramatsu, S. Ueda, Z. Wang, S. Kusano, S. Terakubo, J. O. Trent, S. C. Peiper, N. Yamamoto, H. Nakashima, A. Otaka & N. Fujii, Stereoselective Synthesis of [L-Arg, L/D-3-(2-naphthyl)alanine]-Type (E)-Alkene Dipeptide Isosteres and its Application to the Synthesis and Biological Evaluation of Pseudopeptide Analogues of the CXCR4 Antagonist FC131, J. Med. Chem., 2005, 48, 380-391, DOI: 10.1021/jm049429h 13. T. Kobayakawa, K. Ebihara, Y. Honda, M. Fujino, W. Nomura, N. Yamamoto, T. Murakami & H. Tamamura, Dimeric C34 Derivatives Linked through Disulfide Bridges as New HIV-1 Fusion Inhibitors, ChemBioChem: Special Issue dedicated to the 10th IPS in Kyoto, 2019, 20, 2101-2108, DOI: 10.1002/cbic.201900187
7. H. Tamamura, A. Esaka, T. Ogawa, T. Araki, S. Ueda, Z. Wang, J. O. Trent, H. Tsutsumi, H. Masuno, H. Nakashima, N. Yamamoto, S. C. Peiper, A. Otaka & N. Fujii, Structure-activity Relationship Studies on CXCR4 Antagonists Having Cyclic Pentapeptide Scaffolds, Org. Biomol. Chem., 2005, 3, 4392-4394, DOI: 10.1039/b513145f 14. K. Tsuji, T. Ishii, T. Kobayakawa, N. Ohashi, W. Nomura & H. Tamamura, Fluorescence resonance energy transfer-based screening for protein kinase C ligands using 6-methoxynaphthalene-labeled 1,2-diacylglycerol-lactones, Org. Biomol. Chem., 2021, 19, 8264-8271, DOI:10.1039/d1ob00814e

 

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Celebrating the 20th anniversary of Organic & Biomolecular Chemistry

This year we are proud to be celebrating the 20 years since the launch of Organic & Biomolecular Chemistry

Although the first issue of OBC was published in 2003, the journal is part of a proud history of publications stretching back over 170 years beginning with Journal of the Chemical Society (1849-1965) via Journal of the Chemical Society B and C (1966–1971), and Journal of the Chemical Society, Perkin Transactions 1 and 2 (1972–2002). The vision behind OBC‘s creation was to bring together the synthetic and physical organic strands of Perkin 1 and 2, while incorporating more material relevant to biology. Since that first issue OBC has continued to publish a diverse range of high quality and impactful research in the organic chemistry community. 

We are delighted to announce a range of activities to celebrate the 20th anniversary of OBC. You can find out more about each of these activities below:

 

20th Anniversary Activities

Introductory Editorial

Editorial Board Chair Anthony Davis and Executive Editor Becky Garton introduce the anniversary celebrations with an Editorial: Celebrating the 20th anniversary of Organic & Biomolecular Chemistry

 

20th anniversary collection

We have published an ongoing themed collection featuring work from members of the community who have served on the Editorial and Advisory Boards of OBC across the last two decades. We would like to thank everyone who has been a part of the journal as it would not be where it is today without the support they provided and we appreciate them sharing their latest discoveries with us! Hopefully you enjoy the range of articles featured in the collection.

OBC 20th anniversary collection

 

Community Spotlight Interviews

We will be publishing a series of blogs featuring interviews with authors who have prominently supported OBC by publishing in the journal from our early volumes through to the present day. These blog posts are an opportunity for our authors to give their thoughts on the past twenty years of their research and the encompassing field alongside their insights towards the next two decades.

Professor Hirokazu Tamamura

Professor Luis Domingo

Professor Philip Gale

Professor Dame Margaret Brimble

Professor Guan-Wu Wang

Professor Dhevalapally B. Ramachary

Professor Lei Wang

Professor Alexandra Slawin

Professor Peter Langer

Keep an eye out on our blogs platform and on our socials for future interviews!

 

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Organic & Biomolecular Chemistry welcomes new Associate Editor Cristina Trujillo

We are delighted to welcome our new Associate Editor, Dr Cristina Trujillo to the Organic & Biomolecular Editorial Board!

Dr Cristina Trujillo is a Lecturer in Computational & Theoretical Chemistry at The University of Manchester. She has expertise in highly fundamental topics within Computational Organic Chemistry such as asymmetric catalysis, computationally-led catalysis design, mechanisms of reaction, and non-covalent interactions. Her research interests are focused on the asymmetric catalysis field with particular emphasis on the application of computational techniques in the design of organocatalysts along with the prediction and control of catalytic processes with a direct impact on the development of products with different applications.

Cristina obtained her Ph.D. in Theoretical and Computational Chemistry in 2008 at the Universidad Autónoma de Madrid (Spain). During the period 2008-2016, she held several Postdoctoral positions in Spain (CSIC), Prague (Academy of Sciences), and Ireland (Trinity College Dublin). From 2016 until 2018 she worked at TCD as a Research Fellow before becoming an Assistant Lecturer at TU-Dublin in the School of Chemical & Pharmaceutical Sciences. She has been awarded the very competitive SFI-Starting Investigator Research Grant (SIRG, 2018) and L’Oreal-Unesco Women in Science UK and Ireland Fellowship -Highly Commended (2019). She started as an independent researcher leading her own group at TCD from 2019-2022 before moving to the University of Manchester.

Find out more about Cristina on her website and submit your article to her today!

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Editor’s Collection: Meet the authors – Nathalie Busschaert et al.

Meet our researchers:

Elliot Williams

Hassan Gneid

Sarah Marshall

Mario González

Jorgi Mandelbaum

Nathalie Busschaert


Elliot Williams
obtained his BSc in biochemistry from the University of Central Florida. He is currently working towards his PhD at Tulane University. His PhD focuses on the development of hosts for bacterial lipids, in particular anionic lipids such as PG. As such, he was the first author of the paper and performed the majority of the experiments. When not in the lab, he likes to dance, engage in his community, and walk his dog.

Hassan Gneid completed a BSc in chemistry at Damascus University (Syria), in the field of applied chemistry. After a number of years working in industry, he returned to education in 2011 to complete an MPhil degree in chemistry at the University of Southampton (UK) under the supervision of Dr. Martin Grossel. In 2014, he joined the group of Dr. Jonathan Watts to pursue a PhD in chemistry at the University of Southampton (UK) and the RNA Therapeutics Institute (USA). His PhD work revolved around the use of antisense oligonucleotides for the development of novel antibiotics. Hassan joined the Busschaert group in 2020 as a post-doctoral researcher responsible for microbiology studies. His research interests are oligonucleotide therapeutics and antibiotic development.

Sarah Marshall received her B.S. in biology from the Honors College at East Carolina University in 2015. She continued at East Carolina University to receive her M.S. in chemistry under the supervision of Dr. William E. Allen. During her M.S., she focused on the development of fluorescent amino acids and peptide synthesis. Currently, Sarah is a PhD candidate in the Busschaert group at Tulane University, working on various medical and non-medical applications of synthetic transmembrane anion transporters.

Mario González was born in San Juan, Puerto Rico. In 2019, he received his B.S. in Chemistry from the University of Miami. That same year, he joined the Busschaert group at Tulane University as a graduate student working towards a PhD. His current research involves turning commercially available, nonselective sensors selective via liquid-liquid extractions.

Jorgi Mandelbaum graduated from Tulane University with a B.S. (2021) and M.S. (2022) in neuroscience, with undergraduate minors in chemistry and Spanish. During her studies, she performed undergraduate research in the lab of Dr. Nathalie Busschaert, focusing on PG binding. She currently works as Research Scientist II on the Translational Pharmacology team in the Ophthalmology department at Novartis Institutes for BioMedical Research in Cambridge, MA. With her passion for pharmaceutical development, Jorgi is excited to be continuing her research beyond the academic setting in the healthcare industry.

Nathalie Busschaert born in Antwerp, Belgium, completed a BSc in chemistry at the K. U. Leuven, Belgium, and continued studying for an MSc in chemistry at the same university. She then moved to the University to Southampton (UK) in 2010 to undertake a PhD under the supervision of Professor Philip A. Gale, working on the development of synthetic transmembrane anion transporters. In 2015 she joined the group of Andrew Hamilton at the University of Oxford to work as a post-doctoral researcher. In January 2016 she followed prof. Andrew Hamilton to New York University. She is currently working as an assistant professor at Tulane University. Her research interests are ion transport, lipid binding, membrane processes and medicinal applications of supramolecular systems.


What inspired your research in this area?

We are a young research group (established July 2017), and have been looking for a way to carve out our reputation as supramolecular chemists that work towards medical applications. I have been intrigued by the activity of antimicrobial peptides for a long time, due to my interest in biological membranes. Antimicrobial peptides have long been hailed as a solution to the antibiotic resistance crisis, because they target the bacterial membrane and can cause quick bactericidal activity in bacterial cells. However, they have some drawbacks and have not been able to completely live up to their expectation yet. Most antimicrobial peptides are cationic amphiphilic compounds that function by binding to the negatively charged lipids of bacterial membranes, followed by membrane disruption. During my own PhD that focused on the development of small neutral molecules that can transport chloride anions across biological membranes, we often observed binding to the lipid headgroup in molecular dynamics modelling. While binding to the lipid headgroup is detrimental for anion transport, I hypothesized that binding to the headgroup can provide membrane selectivity (e.g., bacterial membranes over human membranes) and can induce membrane perturbations similar to those observed for antimicrobial peptides. From the start of my independent career, my research group therefore started to develop small molecules that can strongly and selectively bind to bacterial lipid headgroups.

What do you personally feel is the most interesting/important outcome of your study?

The most important outcome of our study is that we provided proof-of-principle that small, neutral, structurally simple molecules can selectively bind to lipid headgroups and that this binding event has sufficient impact on membrane permeability to induce antibacterial activity. Even though the reported compounds were our first attempt at binding PG lipids and have not underwent further optimization yet, we have already achieved relatively potent antibiotics with minimum inhibitory concentrations (MIC values) of 12.5 – 25 μM.

What directions are you planning to take with your research in future? What are you going to be working on next?

We are preparing analogs of the PG hosts reported in this paper (https://doi.org/10.1039/D1OB02298A ), as well as the PE hosts that were reported in our previous OBC paper (https://doi.org/10.1039/D1OB00263E). The aim is to improve the antibacterial activity and lipid selectivity, and to elucidate structure-activity relationships that can help other researchers develop hosts for these two important bacterial lipids. In addition, we would like to investigate the effect of physical membrane parameters (such as curvature, and lipid chain length) on the binding of the hosts to the lipid headgroup. Finally, we are working on developing hosts that can bind selectively to other types of biologically relevant lipids.

Read the full article: A supramolecular host for phosphatidylglycerol (PG) lipids with antibacterial activity

See the other articles showcased in this month’s Editor’s Collection

See all the full articles on our publishing platform

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Editor’s Collection: Meet the authors – Luca Gabrielli et al.

Meet our researchers:

Daniele Rosa-Gastaldo

Vytautas Pečiukėnas

Christopher Hunter

Luca Gabrielli

Daniele Rosa-Gastaldo obtained his PhD in Chemistry at the University of Padova in 2020 under the supervision of Prof. Fabrizio Mancin, studying the use of gold nanoparticles as NMR chemosensors. After a postdoctoral experience at the same university in Dr. Gabrielli’s group, he moved to the University of Geneva and joined as a post-doc Prof. Thomas Bürgi’s group, where his research is focused on the properties and applications of atomically precise gold and silver nanoclusters.

Vytautas Pečiukėnas studied Natural Sciences at the University of Cambridge obtaining MSci diploma in 2018. There he carried out his Masters project on informational oligomers in Prof. Hunter’s group under the direct supervision of Dr. Gabrielli. Currently he is a PhD student in Dr. Josep Cornella’s group at the the Max-Planck-Institut für Kohlenforschung in Germany. His research is focused on developing catalytic cross-coupling protocols by employing Bi(III)/(V) redox platform.

Christopher A. Hunter was born in New Zealand and educated at the University of Cambridge, graduating with a PhD in 1989. He was a lecturer at the University of Otago till 1991, when he moved to the University of Sheffield.  He was promoted to a chair in 1997, and in 2014, he took up the Herchel Smith Professorship of Organic Chemistry at the University of Cambridge. In 2008, he was elected a Fellow of the Royal Society, and he is an Honorary Member of the Royal Irish Academy.

Luca Gabrielli obtained his MSc and PhD in Chemistry at the University of Milano-Bicocca with Laura Cipolla, spending part of his PhD at the Ben G. Davis’ group (University of Oxford). After a post-doc experience with Fabrizio Mancin at the University of Padova, he moved to the group of Chris Hunter (University of Cambridge) as an MSCA-IF fellow. In 2019 he moved back to the University of Padova, where is currently an assistant professor. His research interests span from information molecules to kinetically controlled and out of equilibrium systems.


What inspired your research in this area?

The way living systems store information as a sequence of nucleotides, and how this information is copied, transcribed, and translated into a functional molecule, represents the main inspiration of our research. However, these outstanding properties are currently unique to nucleic acids. Synthetic recognition-encoded oligomers have the potential to display similar properties, which would open the way for the directed evolution of function in synthetic polymers.

What do you personally feel is the most interesting/important outcome of your study?

One of the challenges in the realization of synthetic oligomers capable of sequence-selective duplex formation is the competing intramolecular folding interaction between complementary recognition units. Thanks to the modular approach adopted for designing duplex-forming oligoanilines (Chem. Sci., 2020, 11, 561-566), we investigated how variations in the steric bulk around the H-bond acceptor unit and on the backbone structure would affect folding and duplex formation. We observed that using a long rigid linker as the backbone connecting two monomer units successfully prevents 1,2-folding and leads to the formation of a stable mixed-sequence duplex, while increasing the acceptor bulkiness was not effective in preventing the undesired folding.

What directions are you planning to take with your research in future? What are you going to be working on next?

The observation of imine polymerase activity in one of these single-stranded oligomers (Chem. Sci., 2020, 11, 7408-7414) suggested that more interesting analogies between natural biopolymers and the chemistry of synthetic recognition-encoded oligomers will come to light. Hence, our future research will be focused on developing synthetic duplex-forming oligomers able to perform templated synthesis of the complementary sequence molecule, which is the key property that allows to copy, transcript, and translate nucleic acids.

 

Read the full article: Duplex vs. folding: tuning the self-assembly of synthetic recognition-encoded aniline oligomers

See the other articles showcased in this month’s Editor’s Collection

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Editor’s Collection: Meet the authors – Francesco Sansone et al.

Meet our researchers:

Alessandro Casnati

Jeffrey Esko

Ilaria Morbioli

Francesco Sansone

Yitzhak Tor

Alessandro Casnati received his PhD in Chemistry in 1992 at the University of Parma under the supervision of Prof. Rocco Ungaro. After a period of study in Prof. Reinhoudt’s laboratories at Twente University (NL), he came back to Parma University as Assistant Professor (1994). In 1998 he became Associate Professor and in 2015 Full Professor of Organic Chemistry. His interests are in Supramolecular Chemistry and in the design and synthesis of calixarene receptors for ions, small molecules and of multivalent ligands for macrobiomolecules.

Jeffrey D. Esko, is a Distinguished Professor of Cellular and Molecular Medicine and was a founding Director of the Glycobiology Research and Training Center at the University of California, San Diego. Dr. Esko received his Ph.D. in Biochemistry at the University of Wisconsin in Madison. After an independent fellowship at the Molecular Biology Institute at the University of California, Los Angeles, he moved to the University of Alabama at Birmingham in 1983 as an Assistant Professor and then as a full Professor to the Department of Cellular and Molecular Medicine at the University of California, San Diego in 1996 to help build a program in glycosciences. Work in his laboratory focuses on the structure, biosynthesis, and function of proteoglycans. Current work includes the application of genome-wide methods to identify novel genes involved in glycosaminoglycan assembly; studies focused on treatments for enzyme replacement therapy; studies of proteoglycans in viral and bacterial infection; and studies of proteoglycan-associated receptors with particular emphasis on the vasculature and infection.

Ilaria Morbioli graduated in Chemistry at University of Padua and received her PhD in 2017 under the supervision of Prof. Francesco Sansone working on multivalent calixarenes for the targeting of cell membrane receptors and intracellular cargo delivery. Since 2017 she has been working as researcher at Aptuit, an Evotec Company, which deals with the synthesis of small molecules having pharmacological activity.

Francesco Sansone received his PhD in 1998 in Organic and Supramolecular Chemistry at the University of Parma (Italy), under the supervision of Prof. Rocco Ungaro. Currently, he is Full Professor of Organic and Bioorganic Chemistry at the Department of Chemistry, Life Sciences and Environmental Sustainability, Parma University. With his activity, he significantly contributed to define for calixarenes the role of versatile scaffolds for the preparation of efficient multivalent ligands for biomacromolecules. His research interests are in the design of supramolecular systems for applications in the field of biology and biotechnologies, but also in technological contexts as additives for lubricants and for treatment of radioactive waste.

Yitzhak Tor carried out his doctorate work at the Weizmann Institute of Science earning his PhD in 1990. After a postdoctoral stay at the California Institute of Technology (1990–1993), he took his first faculty position at the University of Chicago. In 1994, he moved to the University of California, San Diego, where he is currently a Distinguished Professor of Chemistry and Biochemistry. He was the Teddy Traylor Scholar in Organic Chemistry (2006–2011) and the George W. and Carol A. Lattimer Professor (2013–2017). His research interests are diverse and include chemistry and biology of nucleosides, nucleotides and nucleic acids, the discovery of novel RNA-targeting antiviral and antibacterial agents, as well as the development of cellular delivery agents and biomolecular fluorescent probes.


What inspired your research in this area?

For some years we have been working on calixarene derivatives that show remarkable ability in delivering nucleic acids into cells thanks to their functionalization with guanidinium and arginine units. Among the functions put into play during the transfection process, these cationic macrocyclic amphiphiles facilitate the cell membrane penetration. Therefore, we decided to exploit this latter property of these macrocycles to improve the uptake of liposomes by cells, with the aim of overcoming some limitations characterizing the action of these lipidic carriers. Liposomes in fact frequently show poor penetration capability and this can significantly impair the beneficial and expected transport of drugs and biologically relevant species for which they are designed. On the other hand, liposomes can be rather simply adorned to gain new properties and functions. We planned thus to improve the liposomes performance by decorating their outer surface with our cationic calixarene-based carriers.

What do you personally feel is the most interesting/important outcome of your study?

I think it is important to have verified that the calixarene derivatives can significantly affect the activity of liposomes, improving their ability of delivering their cargo into the cells. The parallel use of cells lacking anionic polysaccharides on their surface and of plain liposomes (lacking the calixarenes in the outer layer) as references proved the active role played by the cationic macrocycles to trigger the uptake of the calixarene-modified vesicles. I hope these results can be useful to other researchers active in the field of drug delivery to explore the possible use of other similar clustered multivalent polycationic ligands to facilitate cell penetration.

What directions are you planning to take with your research in future? What are you going to be working on next?

Remaining within the context of this specific paper, we are going to work on supramolecular transporters/vectors able to deliver cargos in a targeted way, combining the already-established cell penetrating properties with additional tools such as, for instance, the recognition of specific cells by using antigens units. These latter units should provide the calixarenes with the ability of selectively interacting with specific receptors located only, or overexpressed, in particular tissues, cells and organs. To this end, the calixarene structure typically allows multiple functionalization generating multivalent or multifunctional systems, or even the combination of both natures. The chemistry to obtain such complex systems becomes step by step more challenging.

 

Read the full article: Calixarene-decorated liposomes for intracellular cargo delivery

See the other articles showcased in this month’s Editor’s Collection

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Editor’s Collection: Meet the authors – Yun-Bao Jiang et al.

Meet our researchers:

Professor Yun-Bao Jiang

Dr Xiaosheng Yan

Di Shi

Yun-Bao Jiang is a Professor of Chemistry in the College of Chemistry and Chemical Engineering, Xiamen University, China. He received his PhD from Xiamen University in 1990 under the supervision of Professor Guo-Zhen Chen. He was awarded the distinguished young investigator grant by the NSF of China and has led innovation research teams financially supported by the Ministry of Education and the NSF of China. His current research interests include design and applications of chemical sensors and hierarchical self-assembling systems, with a focus on electron/proton transfer photophysics, metallophilic interactions and supramolecular chirality.

Xiaosheng Yan obtained his PhD degree in analytical chemistry from Xiamen University in 2016 under the supervision of Professor Yun-Bao Jiang. He now is an associate professor in the School of Pharmaceutical Sciences, Xiamen University, China. His research interests are centered on folding and assembling of short peptides for drug discovery, halogen/chalcogen-bonding-driven supramolecular helices, and spontaneous chiral resolution.

Di Shi is a PhD student in Prof. Yun-Bao Jiang’s group in Xiamen University, China. She received her Bachelor’s degree in material chemistry in 2018 from Huaqiao University. Her research focuses on the development of chalcogen bonding driven supramolecular helices and synthesis and applications of macrocyclic molecules, both from folded short peptides.


What inspired your research in this area?

Despite its successful applications as an intermolecular interaction in anion recognition, crystal engineering and catalysis, chalcogen bonding has not been employed to build supramolecular helices. We recently created halogen-bonding driven supramolecular helices from folded short azapeptides containing β-turns, so it was natural for us to explore the potential of chalcogen bonding in driving the supramolecular helices.

What do you personally feel is the most interesting/important outcome of your study?

We recently suggested that a folded short peptide could be an amenable helical building block to form supramolecular helices, allowing good propagation. This study thus confirms that chalcogen bonding can function as an intermolecular interaction to propagate the helicity too. The study may eventually establish a new interaction mode for a supramolecular helix to be built, from helical building blocks containing a chalcogen bonding element.

What directions are you planning to take with your research in future? What are you going to be working on next?

We are exploring the possibility of using chalcogen bonding to build supramolecular helices in the solution phase. The functions of chalcogen bonding in the supramolecular assembled systems will be investigated in the future, for example to examine if the chalcogen bonding can be employed to promote spontaneous chiral resolution.

 

Read the full article: Chalcogen bonding mediates the formation of supramolecular helices of azapeptides in crystals

See the other articles showcased in this month’s Editor’s Collection

See all the full articles on our publishing platform

 

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Editor’s Collection: Anthony Davis

In this month’s Editor’s collection, Chair Anthony Davis shares some of their favourite recent Organic & Biomolecular Chemistry articles

The Organic & Biomolecular Chemistry Editor’s collection is a showcase of some of the best articles published in the journal, hand selected by our Associate Editors and Editorial Board members.

For this month’s selection, Chair Anthony Davis has highlighted some of his favourite recent works.

Take a look at what he thought of the articles below, and find out more about the research and the researchers behind the papers in our interviews with the authors.

Tony’s selection:

Chalcogen bonding mediates the formation of supramolecular helices of azapeptides in crystals
Di Shi, Jinlian Cao, Peimin Weng, Xiaosheng Yan, Zhao Lia and Yun-Bao Jiang

Tony’s comment:
Chalcogen bonding is a fascinating addition to the armoury of supramolecular chemists. In this paper by Yan, Jiang and co-workers it is used in a rational fashion to control molecular conformations. The success of their approach bodes well for future efforts to exploit this under-appreciated phenomenon.

Find out more in our interview with the authors


Calixarene-decorated liposomes for intracellular cargo delivery
Ilaria Morbioli, Alessandro Casnati, Jeffrey D. Esko, Yitzhak Tor and Francesco Sansone

Tony’s comment:
Calixarenes are widely used as synthetic scaffolds for the presentation of multiple functional groups. Tor, Sansone and co-workers show here that calixarenes bearing guanidinium groups can be inserted in liposomes and promote the delivery of contents to cells. The paper nicely exemplifies the efforts of today’s supramolecular chemists to create systems with real-world medical applications.

Find out more in our interview with the authors


Duplex vs. folding: tuning the self-assembly of synthetic recognition-encoded aniline oligomers
Daniele Rosa-Gastaldo, Vytautas Pečiukėnas, Christopher A. Hunter and Luca Gabrielli

Tony’s comment:
It is well-understood how nucleic acids and related molecules can store and transmit information, but the extension of this behaviour to other types of molecules is not well-explored. The Hunter group has investigated duplex formation via hydrogen bonding in carefully-designed oligomers. In collaboration with the Gabrielli group, they here show how unwanted folding can be avoided, pointing towards systems with true information-carrying capacity.

Find out more in our interview with the authors


A supramolecular host for phosphatidylglycerol (PG) lipids with antibacterial activity
Elliot S. Williams, Hassan Gneid, Sarah R. Marshall, Mario J. González, Jorgi A. Mandelbaum and Nathalie Busschaert

Tony’s comment:
In another example of supramolecular chemistry with medical potential, molecules designed to bind anionic lipids are used to target bacterial cell membranes. The systems of Busschaert and co-workers exploit well-known motifs combined in quite simple structures to obtain good selectivity and impressive antibacterial activity.

Find out more in our interview with the authors


Meet the Editor:
Anthony Davis, OBC Chair

Anthony Davis gained a B.A. in Chemistry from Oxford University in 1977, then stayed for a D.Phil. under Dr. G. H. Whitham and postdoctoral work with Prof. J. E. Baldwin. In 1981 he moved to the ETH Zürich as a Royal Society European Exchange Fellow working with Prof. A. Eschenmoser, then in 1982 was appointed Lecturer in Organic Chemistry at Trinity College, Dublin. In September 2000 he moved to the University of Bristol, where he is Professor of Supramolecular Chemistry in the School of Chemistry.

His research focuses on the development of supramolecular systems with potential for biological applications, especially carbohydrate receptors and transmembrane anion transporters. He has co-founded two companies to exploit discoveries in carbohydrate recognition and sensing; Ziylo, which was sold in 2018 to Novo Nordisk, and Carbometrics, which continues to work in the area.

 

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Welcoming Dr S.S.V Ramasastry to the OBC Editorial Board

We are delighted to announce that Dr S.S.V Ramasastry has joined the OBC Editorial Board!

About Ramasastry:

Dr Ramasastry obtained his Ph.D. in Chemical Sciences in 2005 from the Department of Organic Chemistry, Indian Institute of Science, Bangalore (India), under the supervision of Prof. A. Srikrishna. He then pursued postdoctoral studies with Prof. Carlos F. Barbas, III at The Scripps Research Institute, San Diego (USA). After briefly working in industry, he became Assistant Professor in 2011 and then Associate Professor in 2017 at the Department of Chemical Sciences, IISER Mohali.

His research interests include the development of sustainable and atom economic reactions via organophosphine catalysis, palladium-catalyzed allylic alkylation reactions, one-pot cascade transformations employing sulfur ylides, and applying these strategies in the synthesis of bioactive natural products and pharmaceutically important compounds.

Find out more about Ramasastry on his webpage and check out some of his OBC publications below.


Phosphine- and water-promoted pentannulative aldol reaction
Bishnupada Satpathi, Lona Dutta and S. S. V. Ramasastry
Org. Biomol. Chem., 2019, 17, 1547-1551

A computational investigation of the solvent-dependent enantioselective intramolecular Morita–Baylis–Hillman reaction of enones
Nitin Kumar Singh, Bishnupada Satpathi, P. Balanarayan and S. S. V. Ramasastry
Org. Biomol. Chem., 2017, 15, 10212-10220

One-pot relay catalysis: divergent synthesis of furo[3,4-b]indoles and cyclopenta[b]indoles from 3-(2-aminophenyl)-1,4-enynols
Manisha, Seema Dhiman, Jopaul Mathew and S. S. V. Ramasastry
Org. Biomol. Chem., 2016, 14, 5563-5568

Di- and triheteroarylalkanes via self-condensation and intramolecular Friedel–Crafts type reaction of heteroaryl alcohols
Seema Dhiman and S. S. V. Ramasastry
Org. Biomol. Chem., 2013, 11, 8030-8035

Taming furfuryl cations for the synthesis of privileged structures and novel scaffolds
Seema Dhiman and S. S. V. Ramasastry
Org. Biomol. Chem., 2013, 11, 4299-4303


Find out more about our full Editorial Board on our webpage.

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