Possible bi-stable structures of pyrenebutanoic acid-linked protein molecules adsorbed on graphene: theoretical study

• Yasuhiro Oishi,
• Motoharu Kitatani and
• Koichi Kusakabe

Beilstein J. Org. Chem. 2024, 20, 570–577, doi:10.3762/bjoc.20.49

• that similar steric hindrance effects appear when rotation around the alkyl chain occurs. Such an assumption may not be valid when substitutional binding of the linker to the protein causes some effects to the extent which rotation is not defined, such as a strong chemical bond change, a conformational

• proteins is weakly coupled to graphene. It can be concluded that except for bulky structures that allow multiple binding on graphene by several linkers, the above cases will be of a weakly perturbed nature when making a single link for protein capture. Discussion on strategy for improving biosensors The

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• binding affinity to enzyme targets, e.g., acyl-ACP thioesterases, belonging to the protein family of FATs, was demonstrated by using co-crystallization, fluorescence-based thermal shift assays, and chemoproteomics techniques [3]. Likewise, methiozolin (2) is a recently assigned FAT inhibitor that has

• . Accordingly, the target binding affinities were considerably lower than those measured for the strongest analogues 7b, 7c, and 13b. To gain further insights into the biological profile, we chose compounds 7b, 7c, and 13b with promising initial in vivo activity as representatives of our new class of FAT

• pI50 values were calculated from plots of inhibition values vs test compound concentration using Model 205 of the ID Business Solutions Ltd Xlfit software suite. The FAT A binding fluorescent tracer was synthesized from (2S,4S)-4-[(2,6-difluorophenyl)methoxymethyl]-4-ethyl-2-methyl-N-(prop-2

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• first part will be devoted to chemically responsive tweezers, including stimuli such as pH, metal coordination, and anion binding. Then, redox-active and photochemical tweezers will be presented. Keywords: coordination; molecular recognition; molecular switches; photoswitch; redox; supramolecular

• Schrader [3][4], and more flexible variants by Rebek [5][6], Zimmerman [7][8], Bosnich [9] and others [10][11][12]. Initially serving as agents for guest binding and recognition, molecular tweezers have undergone a remarkable evolution, diversifying their applications into the realms of biology, catalysis

• flourished since the early 2000s. It is worth mentioning, as stated by Leigh in a comprehensive review [15], that a pioneering example of a molecular machine was the photoswitchable molecular tweezers developed by Shinkai [16] in 1981 for photocontrolled cation binding. This novel class of tweezers

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• , acetonitrile, and the triflate counterion [66]. Theoretical calculation of binding constants predict that esters coordinate more strongly than alkynes, and water [68]. Alkenes have been shown in some cases to coordinate more strongly than alkynes, but the trend depends on substitution pattern (alkynes can

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• investigated the influence of a modification of 2′-OH in the AMS scaffold with different functional groups on binding to target enzymes and bacterial cell penetration. The inhibitor 7 with a cyanomethyl group at 2′-OH showed desirable inhibitory activity against both recombinant and intracellular gramicidin S

• activities against the A-domain of MbtA, a component of mycobactin synthetase and antimicrobial activities against M. tuberculosis [7]. In addition, aminoacyl (AA)-AMS has been designed to inhibit the amino acid-activating A-domains in NRPSs and has been found to be a tight-binding inhibitor (Figure 2b) [8

• introduced a pegylated biotin linker at the 2′-OH group of ʟ-Phe-AMS and confirmed that the probe retains the binding activities toward the A-domain of GrsA, a gramicidin S synthetase. Aldrich et al. developed a Sal-AMS-based activity-based probe (ABP) to profile MbtA in M. tuberculosis [12]. In contrast, we

Enhanced host–guest interaction between [10]cycloparaphenylene ([10]CPP) and [5]CPP by cationic charges

• Eiichi Kayahara,
• Yoshiyuki Mizuhata and
• Shigeru Yamago

Beilstein J. Org. Chem. 2024, 20, 436–444, doi:10.3762/bjoc.20.38

• . Furthermore, Isobe and co-workers also showed that the carbon nanorings with the simplest structural unit of chiral CNTs, such as cyclochrysenylene [34], cyclonaphthylenes [35], and cycloanthanthrenylene [36], are also excellent hosts of fullerenes with exceptionally high binding constants. These results open

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• the GPR receptor can aggravate the symptoms of myeloid leukemia. In contrast to most GPR84 agonists which contain long alkyl chains, BIMs are not lipophilic molecules, which allow them to bind to the GPR receptor via an allosteric binding site and modulate GPR84’s rate of expression [2]. One

• -effects that it can cause in the more sensitive subgroups of patients. Specifically, when DIM was used in tandem with tamoxifen, the ratio between 2OHE1/16αOHE1 increased up to 229%, as well as the concentration of the sex hormone binding globulin (SHBG) that inhibits the growth of breast cancer cells [4

• related environments [8]. The mechanism of action involves the binding of BIMs to the penicillin-restricting protein PBP2a which inhibits the biosynthesis of the bacterial cell wall, making the treatment feasible without any toxicity to human cells [9][10]. The applications of BIMs have also been extended

Spatial arrangements of cyclodextrin host–guest complexes in solution studied by ¹³C NMR and molecular modelling

• Konstantin Lebedinskiy,
• Ivan Barvík,
• Zdeněk Tošner,
• Ivana Císařová,
• Jindřich Jindřich and
• Radim Hrdina

Beilstein J. Org. Chem. 2024, 20, 331–335, doi:10.3762/bjoc.20.33

• signals in 13C NMR spectra. This signal split can be correlated to the distance of the guest atoms from the wall of the host cavity and to the spatial separation of binding sites preferred by pairs of prochiral carbon atoms. These measurements complement traditional solid-state analyses, which rely on the

• delivery [2][3][4], in analytical and preparative chemistry for compound separation [5] and in materials science for small molecule detection [6][7]. Association (binding) constants between the host and guest molecules [8][9][10] are typically measured by 1H NMR titration [11][12] or isothermal titration

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• garnered attention for their roles as laboratory probes and potential therapeutics. Here, we report the discovery and characterization of Cucumis melo agglutinin (CMA1), a new R-type lectin from melon. Our findings reveal CMA1’s unique glycan-binding profile, mechanistically explained by its 3D structure

• , augmenting our understanding of R-type lectins. We expressed CMA1 recombinantly and assessed its binding specificity using multiple glycan arrays, covering 1,046 unique sequences. This resulted in a complex binding profile, strongly preferring C2-substituted, beta-linked galactose (both GalNAc and Fuca1-2Gal

• ), which we contrasted with the established R-type lectin Ricinus communis agglutinin 1 (RCA1). We also report binding of specific glycosaminoglycan subtypes and a general enhancement of binding by sulfation. Further validation using agglutination, thermal shift assays, and surface plasmon resonance

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• study the mechanism of action of antimicrobial peptides that kill bacteria through binding to these polyprenyls [21][28][29][30][31][32][33][34]. Lipid II has been of particular interest, and during our synthesis of multiple different lipid II analogues, we have developed several optimizations, which we

• in red and antimicrobial-binding motifs highlighted with blue arcs. R1 = H or Ac; R2 = H or Ac; R3 = OH, OMe or NH2; R4 = H or COOH; R5 = Gly5, Ala2, Ala-Ser/Ala or ᴅ-Asp; R6 = OH, OMe or NH2. These structural modifications are described in detail by Münch and co-workers [9]. For more details on

• lipid II-binding antimicrobials, see recent review by Buijs and co-workers [2]. List of i) glycosyl donors and ii) glycosyl acceptors used in this study. Synthesis of disaccharide pentapeptide core 7. Synthesis of lipid II (11) and its analogues 8–10. Optimization of the glycosylation conditions.a

Synthesis of the 3’-O-sulfated TF antigen with a TEG-N₃ linker for glycodendrimersomes preparation to study lectin binding

• Mark Reihill,
• Hanyue Ma,
• Dennis Bengtsson and
• Stefan Oscarson

Beilstein J. Org. Chem. 2024, 20, 173–180, doi:10.3762/bjoc.20.17

• (β-ᴅ-GalNAc-(1→4)-β-ᴅ-GlcNAc), which have then been used for production of the glycodenrimersomes and interaction studies with various galectins [1][2]. In the continuation of this collaboration, to investigate the binding of siglec-1 and the chimera of 3’-SuTF-binding siglecs and TF-binding galectin

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• organic solvents (78–20% in MeCN). The quinolizinium derivatives bind to DNA by intercalation with binding constants of 6–11 × 104 M−1, as shown by photometric and fluorimetric titrations as well as by CD- and LD-spectroscopic analyses. These ligand–DNA complexes can also be established in situ upon

• irradiation of the styrylpyridines and formation of the intercalator directly in the presence of DNA. In addition to the DNA-binding properties, the tested benzo[c]quinolizinium derivatives also operate as photosensitizers, which induce DNA damage at relative low concentrations and short irradiation times

• a change of the DNA structure or occupy binding sites of essential enzymes, which in turn may influence or even inhibit important biochemical processes, for example DNA replication or transcription [1][2]. As a result, the development of DNA-targeting drugs still involves the design of suitable DNA

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• of charges (Figure 1) [13][14][15][16]. Crabtree and co-workers first reported the abnormal binding of an imidazolium salt to an iridium hydride at the C4 carbon atom instead of C2 in 2001 [17][18]. Since then, many other metal complexes bearing imidazol-4-ylidene ligands (F) have been reported [7

Studying specificity in protein–glycosaminoglycan recognition with umbrella sampling

• Mateusz Marcisz,
• Sebastian Anila,
• Margrethe Gaardløs,
• Martin Zacharias and
• Sergey A. Samsonov

Beilstein J. Org. Chem. 2023, 19, 1933–1946, doi:10.3762/bjoc.19.144

• essential to explain their biological functions. In this study, the umbrella sampling (US) approach is used to pull away a GAG ligand from the binding site and then pull it back in. We analyze the binding interactions between GAGs of three types (heparin, desulfated heparan sulfate, and chondroitin sulfate

• GAG properties, especially protein recognition specificity and multipose binding. We found that the binding free energy landscape in the proximity of the GAG native binding pose is complex and implies the co-existence of several binding poses. The sliding of a GAG chain along a protein surface could

• to multipose binding, wherein various configurations of the protein–GAG complex may exhibit similar free binding energies, allowing them to co-exist. Interpreting the “sulfation code”, the amount (net sulfation) and particular positions of the sulfation group (sulfation pattern), could assist in the

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• formation (Figure 1C) [12]. This intriguing mechanism of catalysis should be further intensified on single-walled carbon nanotubes 2 (SWCNTs, Figure 1D) and multi-walled carbon nanotubes 3 (MWCNTs, Figure 1E) [13]. Multiple substrate/transition-state binding should reduce particularly in-plane polarization

• of the π system and thus induced anion–π interactions. Since the polarization caused by substrate/transition-state binding hinders additional binding, this effect should occur only at high concentrations. These expectations were first explored with anion–π catalysis on fullerenes in 2017 [12

• -to-face π stacking because the delocalized π electrons move within the stack away from the charge, which induces a macrodipole along the stack that supports the binding of the anion (Figure 1B) [61]. What works for anion–(π)n–π catalysis on π-stacked foldamers [61] and micelles [8] should apply to

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• , using a new synthesis strategy based on the usage of diazo glutarimide 4 (Scheme 1). Compared to thalidomide (Figure 1), the resulting “benzotriazolo thalidomide” has a similar binding mode, but improved properties, as revealed in crystallographic analyses, affinity assays and cell culture [26]. However

Quinoxaline derivatives as attractive electron-transporting materials

• Zeeshan Abid,
• Liaqat Ali,
• Sughra Gulzar,
• Faiza Wahad,
• Raja Shahid Ashraf and
• Christian B. Nielsen

Beilstein J. Org. Chem. 2023, 19, 1694–1712, doi:10.3762/bjoc.19.124

• separation by reducing Coulomb attraction and exciton binding energy. The resulting enhancement in exciton dissociation and reduced charge recombination contribute to the improved performance of polymer acceptors, especially Qx2 which achieved PCE of 5.32% with PBDB-T donor in an all-PSC device [20]. In a

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• binding guest molecules/ions, but also to undergo unusual transformations, such as metal-induced expansion/contraction. Depending on the design of the particular hybrid, they present unique features involving intriguing redox chemistry, interesting optical properties, and reactivity towards transition

• date back to 1982 when Krishnan and Thanabal reported synthesising a new host molecule with multiple cavities capable of encompassing several guest molecules/ions [39]. The molecule demonstrated an exciting feature of binding Na+, Mg2+, Ca2+, K+, NH4+, and Ba2+ cations. The incorporation of cations

• [46]. The macrotetracycles and macropentacycles, apart from the apparent metal complexation within the porphyrin core, showed cationic guest binding upon adding different ammonium salts, forming 1:1 complexes. Later, in 1985, Camilleri and co-workers reported the synthesis of a capped porphyrin

Complexes of resorcin[4]arene with secondary amines: synthesis, solvent influence on “in-out” structure, and theoretical calculations of non-covalent interactions

• Waldemar Iwanek

Beilstein J. Org. Chem. 2023, 19, 1525–1536, doi:10.3762/bjoc.19.109

• the amine nitrogen of the guest molecule. In addition to hydrogen bonding, other interactions such as π–π stacking and electrostatic interactions also play a role in the complexation process. These interactions can be modulated by changing the pH, solvent, and temperature of the solution. The binding

• affinity and selectivity of the R[4]A–amine complexes depend on several factors, including the size, shape, and functional groups of both the host and the guest molecules. For example, R[4]A derivatives with different substituents on the aromatic rings [12] have been synthesized to enhance the binding

• dipropylamine and diisopropylamine, complexes with a stoichiometry of 1:2 are formed (i.e., 1 molecule of R[4]A binding to 2 molecules of dipropylamine or diisopropylamine). Regardless of the quantity of amine added to the solution of R[4]A in ethanol (4 equiv, 2 equiv, and 1 equiv, respectively), a 1:2

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• often attributed to high binding affinity to DNA, interference with protein biosynthesis, induction of membrane leakage, and affecting GTPase activity in bacteria cell division [12][13][14][15]. Recent reports have also pointed to inhibition of the ‘filamenting temperature-sensitive mutant Z’ (FtsZ

• ) protein [16][17], as well as perturbing carbohydrate metabolism to generate reactive oxygen species that damage the DNA [18], as modes of action for berberine’s antibacterial effects. The antitumor properties of berberine have been attributed to DNA binding, and in particular regulating the activity of

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• ), bear only a single flanking heteroatom and exist as a zwitterionic structure with no neutral canonical resonance form (Figure 3). In this case, binding takes place via the C4 or C5 position. These NHCs have been found to be stronger electron-donors due to the reduced σ-withdrawal from the carbene carbon

• 1,3-dipolar cycloaddition and belongs to the general category of [π4s + π2s] cycloadditions. It is an important method to construct a five-membered heterocyclic ring [66]. As discussed earlier, the Cu atom in NHC–Cu(I) complexes has nucleophilic character, which allows binding to the positive end of

• -donors on the catalytic activity of NHC–Cu(I) complexes for azide–alkyne [3 + 2] cycloaddition reactions [67]. They determined binding constants of four NHC–CuCl complexes with two N-donors, which revealed that addition of phenanthroline to the NHC–CuCl enhanced the catalytic activity manifold. In fact

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• ). The review of Lemaire et al., dedicated to the synthesis of glycerol ether, is complemental to this review article [57]. Of note, the review of Godfroid and Braquet attempted to decipher the binding site of PAF via a QSAR study [58]. 1.1 Synthesis of PAF and some building blocks The platelet

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• numerous similar attributes, halogen bonding has also proven to be a viable alternative in methodologies that rely on hydrogen bond initiation. For example, both halogen- and hydrogen bonding can be used in supramolecular chemistry as the binding mechanism in photoresponsive receptors [73][74][75][76][77

• . used 1H NMR titrations and isothermal titration calorimetry (ITC) to experimentally determine interactions energies for I-9 complexes (e.g., I-9-lig, −6.3 kcal/mol), they also discovered that simultaneous binding to both σ-holes was possible [90]. Given these observations, it is unsurprising that HVI

CO₂ complexation with cyclodextrins

• Cecilie Høgfeldt Jessen,
• Jesper Bendix,
• Theis Brock Nannestad,
• Heloisa Bordallo,
• Martin Jæger Pedersen,
• Christian Marcus Pedersen and
• Mikael Bols

Beilstein J. Org. Chem. 2023, 19, 1021–1027, doi:10.3762/bjoc.19.78

• , are studied as potential CO2 capture agents due to their unique molecular structures and high selectivity towards CO2. In this paper we have investigated binding efficiency of a number of cyclodextrins towards CO2. It is found that the crystal structure of α-cyclodextrin with CO2 has a 1:1

• stoichioimetry and that a number of simple and modified cyclodextrins bind CO2 in water with a Kg of 0.18–1.2 bar−1 (7–35 M−1) with per-O-methyl α-cyclodextrin having the highest CO2 affinity. Keywords: carbon dioxide; crystals; cyclodextrin; gas binding; Introduction The concentration of carbon dioxide (CO2

• CO2 is captured by non-covalent binding. Henglein and Cramer showed many years ago that α-cyclodextrin (1, Figure 1), when treated with CO2 under pressure for several days gave crystals with the gas trapped inside [8]. According to Cramer only 1 was able to form crystals, while larger cyclodextrins

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• chelate environmental Fe3+. Ligand groups, such as hydroxamate, phenolate, catecholate, carboxylate, or oxazoline/thiazoline residues, confer siderophores their high affinity for the binding of Fe3+ [3][4][5]. Following the coordination of the metal, the Fe3+-loaded siderophore complex is transported back