New standards for collecting and fitting steady state kinetic data

• Kenneth A. Johnson

Beilstein J. Org. Chem. 2019, 15, 16–29, doi:10.3762/bjoc.15.2

• a smaller substrate than the preferred one. The induced-fit model proposes a two-step binding pathway in which the substrate first binds to an open form of the enzyme and then the enzyme closes leading to tighter binding and organization of catalytic residues. For decades debate raged as to whether

• step. The substrate binds weakly and then the enzyme closes. If the substrate shows the right geometry (structurally and electrostatically) the closed state is stabilized and organization of catalytic residues leads to fast catalysis. If the substrate is not the right size and shape, the enzyme fails

N-Acylated amino acid methyl esters from marine Roseobacter group bacteria

• Hilke Bruns,
• Lisa Ziesche,
• Nargis Khakin Taniwal,
• Laura Wolter,
• Thorsten Brinkhoff,
• Jennifer Herrmann,
• Rolf Müller and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276

• knowledge on their biosynthesis, the underlying gene organization, as well as their function in many bacteria [11][12][13]. In the Roseobacter group, AHLs are involved, e.g., in antibiotic production [9] or cell differentiation [10]. Although many other bacterial signalling compounds must exist, only few of

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• death according to the World Health Organization [1]. The serendipitous discovery of penicillin and its introduction into the clinic in the first half of the 20th century gave rise to the “Golden Age” of antibiotics discovery and have unquestionably represented one of the most important achievements in

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• Organization (WHO) has published a priority list for pathogens with urgent need for novel treatment options and carbapenem-resistant P. aeruginosa was ranked in the highest category ‘critical’ [12]. One of the main problems we face regarding this Gram-negative bacterium is that it shows a prominent ability to

Transition metal-free oxidative and deoxygenative C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyl lithium as an efficient synthetic approach to azaheterocyclic carboranes

• Lidia A. Smyshliaeva,
• Mikhail V. Varaksin,
• Pavel A. Slepukhin,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2018, 14, 2618–2626, doi:10.3762/bjoc.14.240

• 1-oxide; nucleophilic substitution of hydrogen (SNH); Introduction Dicarbadodecaboranes (carboranes) are known to be 3D polyhedral clusters with a special type of structural organization, relative thermal and chemical stabilities, as well as unique physicochemical properties [1][2][3]. The

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• -Braunschweig, Germany Department of Pharmacy, Saarland University, Saarbrücken, Germany 10.3762/bjoc.14.239 Abstract The rapid development of antimicrobial resistance is threatening mankind to such an extent that the World Health Organization expects more deaths from infections than from cancer in 2050 if

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• ; supramolecular chemistry; tetrathiafulvalene; Introduction Undoubtedly, the exploration of nature’s molecular machines in the last century led to a paradigm change of how we think about working and organization processes on the molecular level [1][2][3]. Inspired by the way how energy and concentration

• . A strategy to stabilize the mixed-valence and radical-cation dimer even at room temperature and to overcome the entropic penalty of their formation is to facilitate a spatial proximity of two or more TTF units by a suitable covalent link [37][38]. This pre-organization can also be generated in

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• chemical calculations were done in several steps: selection of optimal conformers; organization of initial complex geometry; complex optimization procedure. The conformers search procedure has been done only for calix[4]arene’s triazolyl substituents due to complexity of the whole molecule. Conformers of

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• and their optimization at various locations of an organization can become reproducible upon integration through such platforms. While the concept of a unified synthesis platform looks fascinating and useful to reach the targets like ‘Dial-a-molecule’ [45], in reality, it can be very challenging. Some

• made keeping the interest of individual or organization for future. These approaches show the unique and promising ways to make the unified platform to realize the concepts like dial a molecule. Realising the concept of a unified flow synthesis platform possesses some challenges but those can be taken

Selective carboxylation of reactive benzylic C–H bonds by a hypervalent iodine(III)/inorganic bromide oxidation system

• Toshifumi Dohi,
• Shohei Ueda,
• Kosuke Iwasaki,
• Yusuke Tsunoda,
• Koji Morimoto and
• Yasuyuki Kita

Beilstein J. Org. Chem. 2018, 14, 1087–1094, doi:10.3762/bjoc.14.94

• Toshifumi Dohi Shohei Ueda Kosuke Iwasaki Yusuke Tsunoda Koji Morimoto Yasuyuki Kita College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan. Tel: +81-77-561-4908, Research Organization of Science and Technology, Ritsumeikan University, 1-1-1

• work was supported by a Grant-in-Aid for Scientific Research (A) to Y.K. from JSPS and a Grant-in-Aid for Encouragement of Young Scientists (A) and Scientific Research (C) to T.D. from JSPS, and Ritsumeikan Global Innovation Research Organization (R-GIRO) project. T.D. thanks the research fund of the

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• ; Introduction Current cancer chemotherapy Cancer is one of the leading causes of death globally behind the heart and circulatory disorders based on statistics of World Health Organization (WHO) [1]. Among all different types of cancer, the most fatal for males are lung and prostate cancer, while for females are

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• -steroidal drug with anti-inflammatory activity for the treatment of rheumatoid arthritis (RA) in patients with cardiovascular disease [7][8][9]. The World Health Organization has identified HCQ (1) as an essential antimalarial medication for a basic healthcare system, but global access to HCQ (1) has been

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

• extent of secondary chiral organization, thus also allowing a monitoring by ECD spectroscopy [16][17]. The non-degenerate coupled oscillator mechanism is also responsible for generating ECD signals in correspondence with electronic transitions of achiral chromophores surrounded by a chiral environment

• organization of DNA/RNA chromophores (base pairs) in a helical structure, ECD is primarily sensitive to the secondary structure of various nucleic acids and provides characteristic ECD spectra of nucleic acids as a result of base sequence and experimental conditions (see chapter 2.1.). As an example of how the

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• ; multivalency; pre-organization; Review Recognition of carbohydrate ligands For the recognition of carbohydrate ligands, nature has explored binding sites of different shapes and properties. The large family of C-type lectins (CLECs) exhibits carbohydrate-recognition domains (CRDs) which incorporate a calcium

• binding site pre-organization, are more difficult to assess and accordingly have been highlighted in this review. Mannose-binding CLECs are involved in various pathways of the human innate immune response, including the blood dendritic cell antigen 2 (BDCA-2, also known as CD303) [18], langerin (CD207

• desolvation penalty [69][70]. Pre-organization vs flexibility. Carbohydrate–lectin interactions benefit from the low conformational flexibility of pyranoses. This could be impressively demonstrated in a case study comparing a septanose with a manno-configured pyranose derivative [71]. Although in both cases

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• ureas and guanidines currently available in the market. The supramolecular level of organization of thioureas in the solid-state. The supramolecular level of organization of thioureas in the solid-state. In situ Raman spectroscopy monitoring the synthesis of thiourea 28d in the solid-state. N

Molecular recognition of N-acetyltryptophan enantiomers by β-cyclodextrin

• Spyros D. Chatziefthimiou,
• Mario Inclán,
• Petros Giastas,
• Athanasios Papakyriakou,
• Konstantina Yannakopoulou and
• Irene M. Mavridis

Beilstein J. Org. Chem. 2017, 13, 1572–1582, doi:10.3762/bjoc.13.157

• crystals. The disagreement between solution and crystal structure in terms of complex formation and orientation/conformation of the guest indicates that the lattice forces and organization in the crystal prevail by far over the soft host–guest contacts established in solution and determines the final

Chemical systems, chemical contiguity and the emergence of life

• Terrence P. Kee and
• Pierre-Alain Monnard

Beilstein J. Org. Chem. 2017, 13, 1551–1563, doi:10.3762/bjoc.13.155

• effect self-assembly [51]. Thus, mineral surfaces and porous formations could have been excellent media to foster the emergence of “self-contained”, dispersed chemical systems. Furthermore, mineral surfaces can serve as supports for chemical systems to undergo organization. The polymerization of nucleic

• nucleic acid oligomers [53][54][55]. The presence of the mineral support is crucial here as it permits the preservation of the amphiphile bilayer structure during drying, thereby promoting the conversion of an “unreactive” organization (free floating vesicles and free monomers) into reactive chemical

• for the physical organization of molecules into functional catalytic/information networks; iii) systems foster evolutionary processes by maintaining chemicals in close proximity, that is, at physical distances permitting their further reactivity, while allowing for reaction wastes to be disposed of

Grip on complexity in chemical reaction networks

• Albert S. Y. Wong and
• Wilhelm T. S. Huck

Beilstein J. Org. Chem. 2017, 13, 1486–1497, doi:10.3762/bjoc.13.147

• “synthetic moves” We hope that the method developed here allows researchers, and especially chemists, to address important features of self-organization in complex systems. We briefly showed how the tuning of molecular structures allows one to explore the robustness of CRNs. From this perspective, other

• Nature Publishing Group, and [102] copyright 2016 Wiley-VCH Verlag GmbH & Co. Acknowledgements Our work is supported by the Netherlands Organization for Scientific Research (NWO, VICI Grant 700.10.44 (W.T.S.H.)), and funding from the Dutch Ministry of Education, Culture and Science (Gravity program

Framing major prebiotic transitions as stages of protocell development: three challenges for origins-of-life research

• Ben Shirt-Ediss,
• Sara Murillo-Sánchez and
• Kepa Ruiz-Mirazo

Beilstein J. Org. Chem. 2017, 13, 1388–1395, doi:10.3762/bjoc.13.135

• -life simplifications that do not completely erase this aspect at the beginning. The combination of diverse chemical reactions with self-organization and self-assembly processes in heterogeneous, multi-phase conditions could actually be crucial at those first stages: this is the main assumption that

• (individual) organization and (ii) reproduce reliably to spread that type of organization in the population. In practice, this entails becoming autonomous from an energetic point of view (hence the importance of setting up the first energy transduction mechanisms [40]) and achieving regularity in the actual

• oversimplified explanations. First, as we suggested along the previous lines, a combination of evolutionary and organizational principles should be sought. However, this combination should not be simply conceived on a one-dimensional axis (e.g., in terms of the relative weights of ‘self-organization’ vs

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• fashion [58][59]. Therefore, they postulated that by using the correct divalent cation and suitable Lewis acid/Lewis base pairing, the necessary transition-state organization to favor glycosylation of a glycosyl fluoride would outcompete hydrolysis in the aqueous medium. This would lead to a simple non

Strategies in megasynthase engineering – fatty acid synthases (FAS) as model proteins

• Manuel Fischer and
• Martin Grininger

Beilstein J. Org. Chem. 2017, 13, 1204–1211, doi:10.3762/bjoc.13.119

• phosphopantetheinylated [24][32], is located at the tip of the fold opposite to the N- and C-terminal attachment sites. This structural organization likely preserves linkers from interfering in ACP:domain interactions, and, concomitantly, may support the loading of the covalent acyl moiety by steering the acyl tail into

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• information, i.e., they are a molecular reader of the glyco-code. The plethora of three-dimensional structures of lectins, both in unbound form or complexed with oligosaccharides, lead to their organization in a dedicated database, available at http://glyco3d.cermav.cnrs.fr [45]. Information contained in the

• such that antibodies with similar specificity exhibit different selective cell-profiling. Up to now, crystallographic studies of carbohydrate-antibodies mainly concentrated on systems where carbohydrates are complexed with antibody (Fab) or variable fragments (Fv). The organization of a small database

• . While this new investigation corroborated the essential features of the original model, some additional fine details were revealed (Figure 18) [88]. Multiscale organization Cellulose: Knowledge of the structure of a material is necessary to understand its properties. In the case of cellulose, it is also

Correlation of surface pressure and hue of planarizable push–pull chromophores at the air/water interface

• Frederik Neuhaus,
• Fabio Zobi,
• Gerald Brezesinski,
• Marta Dal Molin,
• Stefan Matile and
• Andreas Zumbuehl

Beilstein J. Org. Chem. 2017, 13, 1099–1105, doi:10.3762/bjoc.13.109

• . Monolayers at the air/water interface are well known models for biological membranes, avoiding trans-bilayer leaflet correlation effects [11][12][13][14]. Various techniques exist to probe the surface pressure and the lateral organization of the monolayer [14]. Using monolayers of pure flipper probes, we

• were able to study the fundamental questions of surface pressure–hue correlation avoiding interfering effects from other lipids or solvents. The putative lateral organization of the hydrophobic part of the flipper probes was probed by grazing-incidence angle X-ray diffraction experiments (GIXD) [15][16

• . However, this apparently low slope is connected with the experimental problem of measuring the surface tension of stiff films and the organization of this particular flipper mechanophore. The stiffness of the layer leads to a tilting of the Wilhelmy plate (expansion leads shortly to a surface pressure

Molecular-level architectural design using benzothiadiazole-based polymers for photovoltaic applications

• Vinila N. Viswanathan,
• Arun D. Rao,
• Upendra K. Pandey,
• Arul Varman Kesavan and
• Praveen C. Ramamurthy

Beilstein J. Org. Chem. 2017, 13, 863–873, doi:10.3762/bjoc.13.87

• energy region due to π–π* transitions. A bathochromic shift in the λmax of all thin film spectra of the polymers was observed, as compared to the solution spectra. This is due to the enhanced interchain stacking and ordered structural organization of the polymers in the thin film. The intensity of the

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• synthases are classed according to their intron/exon pattern [47] and their diverse reaction initiation mechanisms [48]. Genomic analyses of plant terpene synthases by Trapp and co-workers [47] revealed general organization of 12–14 introns for Class I terpene cyclases, 9 introns for Class II and 6 introns