Structural diversity in the host–guest complexes of the antifolate pemetrexed with native cyclodextrins: gas phase, solution and solid state studies

• Magdalena Ceborska,
• Magdalena Zimnicka,
• Aneta Aniela Kowalska,
• Kajetan Dąbrowa and
• Barbara Repeć

Beilstein J. Org. Chem. 2017, 13, 2252–2263, doi:10.3762/bjoc.13.222

• complex with α-CD and pseudorotaxane inclusion-type complexes with β-, and γ-CDs. UV–vis titrations at pH 7.4 gave association constants for the obtained complexes. The stability of the complexes increases in the series: α-CD/PTX < γ-CD/PTX << β-CD/PTX. The association of PTX with a monomer cyclodextrin

• experiments in phosphate buffered saline (PBS, pH 7.4) were conducted for evaluation of association constants (Kas). Association of PTX with a monomer CD equivalent – methyl α-D-glucopyranoside – was investigated to fully understand the type of interactions between host and guest molecules. Additionally, the

• . Recent results concerning the studies of association modes between FA and CDs clearly showed that, although the overall gas-phase stabilities do not reflect the solution phase association constants, they are helpful in structural differentiation between inclusion and exclusion complexes [16]. The

p-tert-Butylthiacalix[4]arenes functionalized by N-(4’-nitrophenyl)acetamide and N,N-diethylacetamide fragments: synthesis and binding of anionic guests

• Alena A. Vavilova and
• Ivan I. Stoikov

Beilstein J. Org. Chem. 2017, 13, 1940–1949, doi:10.3762/bjoc.13.188

• receptors for F−, CH3CO2− and H2PO4− ions, which based on the synthesized thiacalix[4]arenes, have been obtained. It was shown that p-tert-butylthiacalix[4]arene tetrasubstituted at the lower rim by N-(4’-nitrophenyl)acetamide moieties bonded to the anions studied with association constants within the range

• 335 nm (see Supporting Information File 1, Figure S18). The complexation ability of the compounds 3, 5 and 6 in relation to the anions (F−, Cl−, Br−, I−, СН3СО2−, Н2РО4−, NO3−) was quantitatively evaluated by the stoichiometry and the association constants (Table 2) of the formed complexes. They were

• determined by the isomolar series method, that all the thiacalix[4]arenes studied form in CHСl3 the 1:1 complexes with selected n-Bu4NX (see Supporting Information File 1, Figure S19). The association constants of the complexes studied were estimated by the dilution method (Figure 2). The appropriate

β-Cyclodextrin- and adamantyl-substituted poly(acrylate) self-assembling aqueous networks designed for controlled complexation and release of small molecules

• Liang Yan,
• Duc-Truc Pham,
• Philip Clements,
• Stephen F. Lincoln,
• Jie Wang,
• Xuhong Guo and
• Christopher J. Easton

Beilstein J. Org. Chem. 2017, 13, 1879–1892, doi:10.3762/bjoc.13.183

• attributed to either steric hindrance by the poly(acrylate) backbone, or hydrophobic association of the adamantyl substituents, or both, hindering complexation. The PAAβ-CDen/PAAADddn system contrasts with the other two systems in that N = 1.45 is consistent with one β-CDen substituent complexing the

• dodecyl tether. Ideally, N = 2 should be observed for such a process, but it appears that either the steric hindrance or hydrophobic association of the adamantyl substituents, or both, restrict N to <2. The 2D NOESY 1H NMR spectrum of the PAAβ-CDen/PAAADddn system confirms the complexation of both the

• and ΔH and more positive TΔS [3]. (The N = 0.86 − 0.83 are also consistent with either the steric hindrance by the poly(acrylate) backbone, or the hydrophobic association of the adamantyl substituents, or both, hindering complexation). The greater stabilities of the PAAβ-CDen/PAAADen and PAAβ-CDen

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• in relation to case reports from Buruli County in Mengo district (today Nakasongola district) in Uganda [20]. Although Bairnsdale ulcer would be the historically more correct denomination, the WHO approved the name Buruli ulcer. Despite the long known association of Buruli ulcer with riverine areas

• specific pathology of M. ulcerans infections [46]. For example, osteomyelitis, a pathology regularly observed in association with M. ulcerans infections in Benin [6] is absent in Australia or Mexico. Likewise, the plaque form of Buruli ulcer which is also found in Benin has not been reported in Australia

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

• . Moreover, trends in enantioselectivity do not follow trends in association constants, i.e., the association constants for the β-CD complexes of both enantiomers of N-acetyltyrosine, N-acetylphenylalanine and N-acetyltryptophan are in decreasing order, whereas their enantioselectivity (ratio of the binding

• . However, as the Job plots suggested, the aliphatic part is influenced by a second host molecule presumably via its secondary side. This implies that in solution, host–guest association is possible through additional orientations and stoichiometry, thus the presence of alternative arrangements in low

• )salicylaldimine complex in ethanol, novel association of β-CD monomers in structures of β-CD complexes, e.g., with 4-pyridinealdazine [30], polyethylene glycol [38] or adamantane [39]. Conclusion This work has been focused on the ability of β-CD to discriminate between the enantiomers of N-acetyltryptophan. NMR

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

• -surfactants, if available via prebiotic syntheses [20][60][61][62], could have also contributed to the formation of primitive amphiphile-based structures, by allowing structure stabilization under prebiotic conditions, e.g., high ionic strength or temperature or stringent pH values. Selective association of

• /association with the chemical system structure or to the encapsulation of a reaction “machinery” within it. Interface-linked catalysis: The oligomerization of peptides from amino acids with condensing agents has been demonstrated to occur in the presence of phospholipid vesicles [65][66][67]. In these studies

• association with the interface of chemical systems. For instance, the activity of an RNA polymerase ribozyme was improved when the various RNA compounds of the system (the ribozyme, the template/primer) were derivatized with amphiphilic moieties and co-associated within micelle structures [69]. Although no

An improved preparation of phorbol from croton oil

• Alberto Pagani,
• Simone Gaeta,
• Andrei I. Savchenko,
• Craig M. Williams and
• Giovanni Appendino

Beilstein J. Org. Chem. 2017, 13, 1361–1367, doi:10.3762/bjoc.13.133

• once used in human medicine as a topical rubefacient and in veterinarian medicine as a strong laxative [1], but nowadays its only medical use is in rejuvenating esthetic surgery in association to blepharoplasty, a practice that was mastered in the 1960s capitalizing on the potent exfoliating activity

• of the oil, especially in association to phenol [3]. The extraordinarily obnoxious and vesicant properties of croton oil have fostered studies aimed at the identification of its active principles since the very early developments of organic chemistry. Thus, the first chemical study on croton oil was

Biomimetic molecular design tools that learn, evolve, and adapt

• David A Winkler

Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125

• biological probes synthesized by automated synthesis by iterative coupling of different building blocks (colors). TBDPSE, tert-butyldiphenylsilylethyl; TMSE, trimethylsilylethyl. Adapted with permission from [37]; copyright 2015 American Association for the Advancement of Science. An example of a composition

Sugar-based micro/mesoporous hypercross-linked polymers with in situ embedded silver nanoparticles for catalytic reduction

• Qing Yin,
• Qi Chen,
• Li-Can Lu and
• Bao-Hang Han

Beilstein J. Org. Chem. 2017, 13, 1212–1221, doi:10.3762/bjoc.13.120

• support of the National Natural Science Foundation of China (Grants 21574031, 21374024, and 21574032), the Ministry of Science and Technology of China (Grant No. 2014CB932200), and CAS Youth Innovation Promotion Association is acknowledged.

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

• tool for the investigations of the state of materials in solution at the nanoscale. Many studies have been devoted to polysaccharides, for which structural change have been observed in real time. There exists extensive literature on this subject and the role played by polysaccharide association

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• consequence is that this is an abstract way to create an association between matter and information, exactly as the integer “3” can be coded in a variety of languages (e.g., three, trois, τρια, ). The one-to-one correspondence of complementary strands in nucleic acids was a straightforward coding process, but

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

• : Surface pressure/area per molecule isotherms, energy minimized structures of the flipper mechanophore, GIXD heightmaps, and IRRAS data. Acknowledgements Parts of this research were carried out at PETRA III at DESY, a member of the Helmholtz Association (HGF). We would like to thank Dr. Uta Ruett and Dr

G-Protein coupled receptors: answers from simulations

• Timothy Clark

Beilstein J. Org. Chem. 2017, 13, 1071–1078, doi:10.3762/bjoc.13.106

• bound. The α-subunit of the G-protein is shown in green, β in yellow and γ in magenta. In this state, the GPCR exhibits basal activity. This figure assumes pre-association of the G-protein to the receptor. (b) Fully activated GPCR. Both an agonist ligand and the G-protein are required for full

How and why kinetics, thermodynamics, and chemistry induce the logic of biological evolution

• Addy Pross and
• Robert Pascal

Beilstein J. Org. Chem. 2017, 13, 665–674, doi:10.3762/bjoc.13.66

• required by the Second Law (Figure 1A). With regard to living organisms, the situation is more complex. On the one hand, association processes directly driven by the Second Law are common in living organisms (e.g., protein folding, the assembly of protein sub-units through molecular recognition, assembly

• species which can interact, leading to macromolecular structures or patterns [18]. The kinetic stability of the organised structures in those cases is associated with energy dissipation from an activating agent able to convert some reactant into transient species able to undergo intermolecular association

• forward by Lynn Margulis [71] half a century ago to explain eukaryotic cell formation is in fact just a particularly striking example of a cooperative association in action. It is also important to emphasise that cooperation may either have involved a physical linkage between different components through

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• . (Reproduced with permission from [43], copyright 2016 American Association for the Advancement of Science). Reconfigurable modules and flowcharts for API synthesis. (Reproduced with permission from [85], copyright 2016 American Association for the Advancement of Science). Reconfigurable system for continuous

• production and formulation of APIs. (Reproduced with permission from [85], copyright 2016 American Association for the Advancement of Science). A flow microreactor system for the generation and trapping of highly unstable carbamoyllithium species. Flow synthesis of functionalized α-ketoamides. Reactions of

• microreactor system. Control of anionic Fries rearrangement reactions by using submillisecond residence time. (Adapted with permission [43], copyright 2016 American Association for the Advancement of Science). Flow microreactor system for lithiation, borylation, Suzuki–Miyaura coupling and selected examples of

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• dispersion of this nucleus. The authors determined the association constant of the complex of NaPF6 with α-cyclodextrin at the picomole level with a detection volume of 50 nL and using non-deuterated solvents [25]. To conclude with the different coil geometries, microslot NMR microprobes and stripline coils

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• relationship study. Ultimately, we wish to synthesize chemical probes of glorin for the identification of the unknown glorin receptor. Experimental Quantitative reverse transcription PCR: P. pallidum PN500 cells were cultured in association with Escherichia coli K12 cells. Cells were harvested before first

• for financial support from the Leibniz Association, and the Fonds der Chemischen Industrie (VCI) (P.S.). This work was also supported by the DFG-funded graduate school of excellence Jena School for Microbial Communication (R.B. and D.R.).

Interactions between photoacidic 3-hydroxynaphtho[1,2-b]quinolizinium and cucurbit[7]uril: Influence on acidity in the ground and excited state

• Jonas Becher,
• Daria V. Berdnikova,
• Darinka Dzubiel,
• Heiko Ihmels and
• Phil M. Pithan

Beilstein J. Org. Chem. 2017, 13, 203–212, doi:10.3762/bjoc.13.23

• acidity or basicity. In fact, it was shown that the pKa of organic acids and bases often shifts by orders of magnitude upon association with CB[n] [16][17][18][19][20][21][22][23][24], which may be used, e.g., to modify catalytic activity [6] or for sensing purposes [7]. Notably, the same effect was

• -wavelength emission at 571 nm was quenched to a lesser extent. To assess the influence of the association of the ligand 2 with CB[7] on its acidity, photometric and fluorimetric acid–base titrations were performed with the complex (Figure 7). Such as in the case of the unbound ligand, the absorption bands

• –guest association. Thus, the titration curve at pH 5 reveals the association of 2 with CB[7] to result in only one absorbing complex, as clearly indicated by the formation of an isosbestic point. At pH 7, however, no isosbestic points are formed, presumably because of already considerable deprotonation

Dynamics and interactions of ibuprofen in cyclodextrin nanosponges by solid-state NMR spectroscopy

• Monica Ferro,
• Franca Castiglione,
• Nadia Pastori,
• Carlo Punta,
• Lucio Melone,
• Walter Panzeri,
• Barbara Rossi,
• Francesco Trotta and
• Andrea Mele

Beilstein J. Org. Chem. 2017, 13, 182–194, doi:10.3762/bjoc.13.21

• the reflexes of IbuNa, shown in upper traces of the figure (Figure 10f). As a final remark, the PXRD patterns show that ibuprofen entrapped into the nanosponge network still retains crystallinity, thus confirming that the formation of the polymer-drug association is a mild process. Conclusion The

Phosphated cyclodextrins as water-soluble chiral NMR solvating agents for cationic compounds

• Cira Mollings Puentes and
• Thomas J. Wenzel

Beilstein J. Org. Chem. 2017, 13, 43–53, doi:10.3762/bjoc.13.6

• . Equation 1 and Equation 2 show the association of the (R)- and (S)-enantiomers of a substrate (Sub) with a chiral solvating agent (CSA). Provided that the exchange of substrates with the CSA is fast on the NMR time scale, there are two mechanisms through which chiral solvating agents (CSAs) can cause

• enantiomeric differentiation. The first is that the complexes of the two enantiomers of the substrate with the enantiomerically pure CSA are diastereomers and therefore exhibit different chemical shifts. The second relies on a frequently observed difference in the association constants of the two enantiomers

• . In those cases where enantiomeric differentiation occurs solely through differences in association constants of the two enantiomers of the substrate with the P-CD, the magnitude of the enantiomeric differentiation may decrease at increasing P-CD concentrations from 5 to 20 mM. In this situation, the

Stabilization of nanosized titanium dioxide by cyclodextrin polymers and its photocatalytic effect on the degradation of wastewater pollutants

• Tamás Zoltán Agócs,
• István Puskás,
• Erzsébet Varga,
• Mónika Molnár and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2016, 12, 2873–2882, doi:10.3762/bjoc.12.286

• occur depending on the conformation of the host–guest complex (if the light-sensitive part of the molecule is located within or outside of the cavity), on the complex association constant and on the concentration ratio of the guest to the CD. It was shown that the photodecomposition of MB was enhanced

• by stabilizing Ag/TiO2 nanoparticles with β-CD, but applying β-CD in excess the rate of degradation decreased dramatically [46]. The association constant of IBR/β-CD complex falls in the range of 103–104 M−1 [47][48], while that of MB/β-CD is less than 103 M−1 [49][50]. According to NMR studies IBR

• is deeply included into the cavity [51], while MB is too large to be completely shielded by complexation. The too strong association between IBR and the cavities of CMBCD-P can be a possible reason of protection instead of catalytic decomposition in this process. Further experiments are needed to

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• and Michael Hoffmann (Helmholtz Institute for Pharmaceutical Research Saarland, HIPS) for HRMS measurements. We are grateful to the Helmholtz Association (grant no. VH-NG-934) and the Deutsche Forschungsgemeinschaft (grant no. Ti756/2-1) for financial support.

Direct arylation catalysis with chloro[8-(dimesitylboryl)quinoline-κN]copper(I)

• Sem Raj Tamang and
• James D. Hoefelmeyer

Beilstein J. Org. Chem. 2016, 12, 2757–2762, doi:10.3762/bjoc.12.272

• ) intermediate may be well-stabilized by boron as a Z-type ligand, and the mesityl groups surrounding boron may favor the association of arenes for the deprotonation–metalation and the oxidative addition steps. Wang et al. proposed concerted metalation–deprotonation via a sigma bond metathesis involving a cyclic

Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

• Markus Menke,
• Pardha Saradhi Peram,
• Iris Starnberger,
• Walter Hödl,
• Gregory F.M. Jongsma,
• David C. Blackburn,
• Mark-Oliver Rödel,
• Miguel Vences and
• Stefan Schulz

Beilstein J. Org. Chem. 2016, 12, 2731–2738, doi:10.3762/bjoc.12.269

• towards a biological evaluation of the gland secretion and its compounds to understand their real function in the behavior of the frogs. Although no experimental evidence has been obtained so far, the close association of the innervation of the gland with the mating period, its location and use during

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• binding constants between CDs (α- or γ-CD) and short phospholipids (i.e., diheptanoylphosphatidylcholine, DHPC) [63]. In this study, the association constants were estimated from 1H NMR measurements. The results proved that the K1 values are in the order α-CD < γ-CD while the K2 values are in the order γ

• ]. In the same idea, Mascetti et al. proposed that CDs interact directly with cholesterol [82]. Based on molecular simulations, López et al. proposed the following mechanism: i) association of CDs in aqueous solution to form dimers, ii) binding of dimers at the membrane surface, iii) extraction and

• logical that D-glucose interacts weakly with native CDs due to its size and its hydrophilic property. However, from these conflicting results, Turner proposed to use kinetic measurements to determine the association constants of several sugars with β-CD [98]. This new method has been published in 2000 [99