A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• bind 9-propyladenine in chloroform with a very high association constant of Kassoc = 120,000 M−1 [17][18][19]. What role do the hydrogen bonding and aromatic stacking play? As seen in Figure 4, this system provides an excellent example of what Jencks called “complex additivity of binding energies” [20

• homologous series of alkanes, not an analysis of a host–guest system. All these values suggest that freezing out a single bond rotation is not terribly costly but association constants can drop significantly if too much flexibility exists; freezing five single bonds within a complex would lower its stability

• Institutes of Health (R01 AR058361), the Muscular Dystrophy Association (295229), and the National Science Foundation (CHE-1307404). I want to thank all of my wonderful students who have made this journey possible. Only some of their work could be included in this review, but I am grateful to them all. This

Supramolecular structures based on regioisomers of cinnamyl-α-cyclodextrins – new media for capillary separation techniques

• Gabor Benkovics,
• Ondrej Hodek,
• Martina Havlikova,
• Zuzana Bosakova,
• Pavel Coufal,
• Milo Malanga,
• Eva Fenyvesi,
• Andras Darcsi,
• Szabolcs Beni and
• Jindrich Jindrich

Beilstein J. Org. Chem. 2016, 12, 97–109, doi:10.3762/bjoc.12.11

• between the cinnamyl moiety and the α-CD cavity would not be strong enough to hold together such large aggregates. According to Boutellier [15] the degree of polymerization (DPmax) for a SP is given by the association constant between the interacting components and by the concentration of the self

Supramolecular polymer assembly in aqueous solution arising from cyclodextrin host–guest complexation

• Jie Wang,
• Zhiqiang Qiu,
• Yiming Wang,
• Li Li,
• Xuhong Guo,
• Duc-Truc Pham,
• Stephen F. Lincoln and
• Robert K. Prud’homme

Beilstein J. Org. Chem. 2016, 12, 50–72, doi:10.3762/bjoc.12.7

• permeation chromatography and light scattering methods [48]. In 2002, Karlson et al. found that hydrophobic association among the hydrophobic substituents of substituted poly(ethylene glycol) was disrupted by host–guest complexation by methylated α-CD [42]; as was a similar association by the hydrophobic

• thickening occurs. 1.3 Recovery of hydrophobic association Hydrophobic associations in substituted polymer solutions may be recovered by adding other guest species which form more stable cyclodextrin host–guest complexes than the polymer substituents do [41][45][46][50]. Thus, Khan et al. used nonionic

• surfactants based on poly(ethylene glycol) to recover the hydrophobic associations in hydrophobically substituted alkali-soluble emulsion (HASE) polymers complexed by α-CD and β-CD [41]. (It should be noted that association occurs between hydrophobically substituted polymers in aqueous solution and that this

Determination of formation constants and structural characterization of cyclodextrin inclusion complexes with two phenolic isomers: carvacrol and thymol

• Miriana Kfoury,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2016, 12, 29–42, doi:10.3762/bjoc.12.5

• phase solubility profiles are generally apparent values that combine several effects on the guest solubility: inclusion complexation, self-association of poorly soluble guests, self-aggregation of CD:guest complexes, as well as non-inclusion interaction and micelles formation [38]. The solubilizing

Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin–steroid interaction

• Mino R. Caira,
• Susan A. Bourne,
• Halima Samsodien and
• Vincent J. Smith

Beilstein J. Org. Chem. 2015, 11, 2616–2630, doi:10.3762/bjoc.11.281

• information such as the values of the association constants for complex formation in solution. Thus instead, the simpler expedient of determining the solubility of 2ME in a series of aqueous solutions of both native and derivatised cyclodextrins of known concentrations (typically 2% m/v) was initially

Smart molecules for imaging, sensing and health (SMITH)

• Bradley D. Smith

Beilstein J. Org. Chem. 2015, 11, 2540–2548, doi:10.3762/bjoc.11.274

• was vital for efficient rotaxane formation. The interlocked molecule retained its salt binding ability and association of the ions modulated the rotaxane structural dynamics [33][34]. Squaraine rotaxanes The interests in molecular imaging and rotaxane structures merged in 2005 with the discovery and

• , it has to clearly show a pathway that leads to valuable new technologies. Effective biomolecule recognition requires both strong affinity and high selectivity, and for investigators who wish to develop association systems that operate effectively in water I offer two words of advice “surface area

• and self-assembly processes that are crucial for cell growth and signaling. These precisely controlled association systems have been refined over billions of years of evolution. The selective recognition is driven by protein–protein interactions that operate at an interface with a surface area that is

Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations

• Giuseppina Raffaini,
• Antonino Mazzaglia and
• Fabio Ganazzoli

Beilstein J. Org. Chem. 2015, 11, 2459–2473, doi:10.3762/bjoc.11.267

• investigated the association behaviour of eight molecules in vacuo to model an apolar, weakly interacting solvent. To this purpose, we randomly placed the molecules with an unbiased arrangement in a cubic cell with a size of 61.5 Å using periodic boundary conditions (Figure 9a). The initial minimization

• nanostructure could be viewed as the building block of a vesicle surface [37]. In any case, the radius of gyration of the two clusters are essentially equal, since they amount to 12.01 Å and 12.09 Å, respectively, showing again the relatively loose association achieved in water in this stage. It should be

Size-controlled and redox-responsive supramolecular nanoparticles

• Raquel Mejia-Ariza,
• Gavin A. Kronig and
• Jurriaan Huskens

Beilstein J. Org. Chem. 2015, 11, 2388–2399, doi:10.3762/bjoc.11.260

• synthesized by a reaction of 1-(chlorocarbonyl)ferrocene with the terminal amino group of methoxypoly(ethylene glycol)amine (Mw = 5000 g/mol) in dichloromethane, using an excess of triethylamine as a base, followed by precipitation from diethyl ether. To evaluate the association constant of the Fc moiety with

Co-solvation effect on the binding mode of the α-mangostin/β-cyclodextrin inclusion complex

• Chompoonut Rungnim,
• Sarunya Phunpee,
• Manaschai Kunaseth,
• Supawadee Namuangruk,
• Kanin Rungsardthong,
• Thanyada Rungrotmongkol and
• Uracha Ruktanonchai

Beilstein J. Org. Chem. 2015, 11, 2306–2317, doi:10.3762/bjoc.11.251

• phase-solubility studies were carried out in order to assess complex formation, with the mechanism of association being probed using a mathematical model. It was found that α-MGS was poorly soluble at low ethanol concentrations (0–10% v/v), but higher concentrations (10–40% v/v) resulted in better α-MGS

• directly related to the concentration of free α-MGS [D], the concentration of β-CD, and the apparent binary complexation constant, Kbapp, which can be determined according to Equation 4. Furthermore, the apparent binary complexation constant, Kbapp, has an association with the co-solvent concentration [C

Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition

• Nicolas Desbois,
• Sandrine Pacquelet,
• Adrien Dubois,
• Clément Michelin and
• Claude P. Gros

Beilstein J. Org. Chem. 2015, 11, 2202–2208, doi:10.3762/bjoc.11.239

• contrast agent [14][15]. Copper-64. Despite the emerging recognition of 64Cu as a suitable radioisotope in positron emitting tomography (PET) imaging (t1/2 = 12.7 h, β+: 17.4%, Eβ+max = 656 keV; β−: 39%, Eβ-max = 573 keV), there is actually only few examples of the association of 64Cu2+-labeled NOTA/DOTA

Conformational equilibrium in supramolecular chemistry: Dibutyltriuret case

• Karina Mroczyńska,
• Małgorzata Kaczorowska,
• Erkki Kolehmainen,
• Ireneusz Grubecki,
• Marek Pietrzak and
• Borys Ośmiałowski

Beilstein J. Org. Chem. 2015, 11, 2105–2116, doi:10.3762/bjoc.11.227

• . Box 35, FI-40014, Jyväskylä, Finland 10.3762/bjoc.11.227 Abstract The association of substituted benzoates and naphthyridine dianions was used to study the complexation of dibutyltriuret. The title molecule is the simplest molecule able to form two intramolecular hydrogen bonds. The naphthyridine

• salt was used to break two intramolecular hydrogen bonds at a time while with the use of substituted benzoates the systematic approach to study association was achieved. Both, titrations and variable temperature measurements shed the light on the importance of conformational equilibrium and its

• influence on association in solution. Moreover, the associates were observed by mass spectrometry. The DFT-based computations for complexes and single bond rotational barriers supports experimental data and helps understanding the properties of multiply hydrogen bonded complexes. Keywords: association

Ru complexes of Hoveyda–Grubbs type immobilized on lamellar zeolites: activity in olefin metathesis reactions

• Hynek Balcar,
• Naděžda Žilková,
• Martin Kubů,
• Michal Mazur,
• Zdeněk Bastl and
• Jiří Čejka

Beilstein J. Org. Chem. 2015, 11, 2087–2096, doi:10.3762/bjoc.11.225

• , but most probably with the slow initiation rate. If initiation starts by coordination of the substrate molecule to the Ru atom (association and interchange mechanism [36]), the steric conditions around the Ru atom may be important. The very low initiation rate with methyl oleate may implicate some

Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Yumi Hirai,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2015, 11, 2079–2086, doi:10.3762/bjoc.11.224

• reference wavelength of 630 nm was measured with a microplate reader (Bio-Rad Model 550, Tokyo, Japan). Cellular association of Lac-β-CyD Cellular association of Lac-β-CyD was determined by a flow cytometry. After incubation with TRITC-Lac-β-CyD for 1 h in U18666A-treated HepG2 cells, the cells were washed

• 100 μL of medium containing 1 mM β-CyDs for 24 h at 37 °C. After washing once with PBS, 100 μL of fresh HBSS and 10 μL of WST-1 reagent were added to plates, and incubated for 30 min at 37 °C. Each value represents the mean ± S.E.M. of 6–8 experiments. Cellular association of TRITC-Lac-β-CyD in

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• peptides (AMPs) [4] and ceragenins I (Figure 1) [5]. These CSAs selectively bind to the over expressed negatively charged peripheral phospholipids on the internal bacterial cell membranes. Following membrane association, deformation occurs causing bilayer destabilization and cell lysis [6]. According to

Star-shaped tetrathiafulvalene oligomers towards the construction of conducting supramolecular assembly

• Masahiko Iyoda and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2015, 11, 1596–1613, doi:10.3762/bjoc.11.175

• -active nanostructures in the solid state were summarized so far. Therefore, this review focuses on the conducting nanostructures of TTF derivatives in the solid state, together with association behavior in solution. Review Redox-active radially expanded TTF oligomers in solution and the solid state TTF

• showed two reversible two-electron redox waves at −0.03 and 0.38 V vs Fc/Fc+ in benzonitrile under normal conditions [25][60]. Conducting nanostructure formation from star-shaped oligo-TTFs Although pristine TTF does not self-associate in solution due to the low association constant for dimerization, the

• File 1). The self-association behavior is significantly affected by the solvent. While no association was observed in benzene-d6 solution in the concentration ranges of 0.7–21 mM even at low temperatures, a larger K2 value was estimated in CDCl3–CD3CN solution (3:7 v/v, K2 = 5.01 ± 0.98 M−1 at 293 K

Latent ruthenium–indenylidene catalysts bearing a N-heterocyclic carbene and a bidentate picolinate ligand

• Thibault E. Schmid,
• Florian Modicom,
• Adrien Dumas,
• Etienne Borré,
• Loic Toupet,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 1541–1546, doi:10.3762/bjoc.11.169

• ][19]. Nevertheless, indenylidene complexes, that have notably showed an improved stability in comparison to their benzylidene counterparts [20][21][22], have never been considered in association with picolinic ligands for the synthesis of robust latent catalysts. Moreover, this strategy would provide

• work was supported by the Agence Nationale de la Recherche (ANR) (ANR-12-CD2I-0002 Cflow-OM), Oméga Cat System and the Association Nationale de la Recherche et la Technologie (ANRT, grant to A.D.). M.M. and O.B. thank the Centre National de la Recherche Scientifique (CNRS) and the Ecole Nationale

Tetrathiafulvalene-based azine ligands for anion and metal cation coordination

• Awatef Ayadi,
• Aziz El Alamy,
• Olivier Alévêque,
• Magali Allain,
• Nabil Zouari,
• Mohammed Bouachrine and
• Abdelkrim El-Ghayoury

Beilstein J. Org. Chem. 2015, 11, 1379–1391, doi:10.3762/bjoc.11.149

• devoted to the association of a binding or coordinating unit to the redox-active TTF moiety. This strategy has led for example, in solid state, to the preparation of electroactive metal complexes that combine magnetic and electrical properties [12][13][14][15][16][17]. In solution, TTF-based redox

Surprisingly facile CO₂ insertion into cobalt alkoxide bonds: A theoretical investigation

• Willem K. Offermans,
• Claudia Bizzarri,
• Walter Leitner and
• Thomas E. Müller

Beilstein J. Org. Chem. 2015, 11, 1340–1351, doi:10.3762/bjoc.11.144

• ethylmethylimidazolium chloride, CO2, and propylene oxide (complex c in [37]) and for the association complex of [Ni(OH)(pincer ligand)] and CO2 [50]. The calculations for the product state (PS) revealed an optimized structure for each ligand L, whereby the carbonate chain was coordinated in a mono-dentate fashion to

Synthesis of photoresponsive cholesterol-based azobenzene organogels: dependence on different spacer lengths

• Yuchun Ren,
• Bin Wang and
• Xiuqing Zhang

Beilstein J. Org. Chem. 2015, 11, 1089–1095, doi:10.3762/bjoc.11.122

• new classes of organogelator architectures have been systematically studied because of their reversible gel process and unique directional self-association through weak van der Waals interactions [16][17]. Up to now, numerous attempts have been made to develop novel supramolecular architectures, which

• the same vibrational area. The peak observed at 3437cm−1 can be assigned to the intermolecular association hydrogen stretching vibration. However, the band of ethanol, isopropanol and 1-butanol shifted to 3438, 3439 and 3440 cm−1, respectively. The comparison of the IR spectra of powder and gels

Glycoluril–tetrathiafulvalene molecular clips: on the influence of electronic and spatial properties for binding neutral accepting guests

• Yoann Cotelle,
• Marie Hardouin-Lerouge,
• Stéphanie Legoupy,
• Olivier Alévêque,
• Eric Levillain and
• Piétrick Hudhomme

Beilstein J. Org. Chem. 2015, 11, 1023–1036, doi:10.3762/bjoc.11.115

• realized on this system [59]. By comparison with these results observed for molecular clip 15 [58], it is clear that clips 1–3 exhibit [(TTF)2]+˙ mixed-valence dimer and/or (TTF+˙)2 dimer species but their self-association organization could not be yet demonstrated. The presence of more or less sterically

• , confirming the formation of the 1:1 complex (m-DNB@clip 3) (Figure 9 left). The association constant was determined to be Ka = (7 ± 3) × 103 M−1 by exploiting the Job plot analysis according to literature [66]. Despite many efforts devoted to the search for a complexation of m-DNB using molecular clip 4, we

• addition of sensor 4. The construction of the Job plot is in agreement with the 1:1 binding stoichiometry between clip 4 and F4-TCNQ with a maximum centered at a molar ratio of 0.5 (Figure 9 right). The high association constant Ka = (1.3 ± 0.8) × 106 M−1 in CH2Cl2 confirms that this rigidified molecular

Novel carbocationic rearrangements of 1-styrylpropargyl alcohols

• Christine Basmadjian,
• Fan Zhang and
• Laurent Désaubry

Beilstein J. Org. Chem. 2015, 11, 1017–1022, doi:10.3762/bjoc.11.114

• 16. Optimization of the acid-catalyzed rearrangements of enynol 2. Supporting Information Supporting Information File 218: Experimental procedures for the synthesis of compounds 7–9, 13, 14 and 17–28. Acknowledgements L.D. was supported by the "Association pour la Recherche sur le Cancer" (ARC). We

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• from the data obtained for the sample lane (Fc2-Fc1, Figure S11, Supporting Information File 1). The association phase was followed by a 180 s dissociation phase. Washing and regenerating of both lanes was done by injecting 4 M MgCl2. For KD determination, chips were loaded to one third with the

Discrete multiporphyrin pseudorotaxane assemblies from di- and tetravalent porphyrin building blocks

• Mirko Lohse,
• Larissa K. S. von Krbek,
• Sebastian Radunz,
• Suresh Moorthy,
• Christoph A. Schalley and
• Stefan Hecht

Beilstein J. Org. Chem. 2015, 11, 748–762, doi:10.3762/bjoc.11.85

• association strongly, no selective deprotonation of the porphyrin core has been attempted. The preparation of the corresponding crown ether hosts (Scheme 2) involved an initial Williamson ether synthesis in which catechol (17) was first extended with 2-[2-(2-chloroethoxy)ethoxy]ethanol to diol 18, which was

• -8 C1 as well as of C2 and C4 with monovalent dibenzylammonium A1 (Figure 2, top), followed by the results obtained for the multivalent 1:1 and 2:1 complexes A2@C2, A22@C4, A4@C22 and A4@C4 (Figure 2, bottom). [3]- and [5]pseudorotaxanes from monovalent building blocks First the association of A2 and

• the appearance of a new set of signals due to slow exchange rates on the NMR-time scale, could be observed. Upon association the benzyl signals Hb/c shift downfield by approximately +0.3 ppm and split into two separate pair of signals, which is typical for a complexation of C1 with a dibenzylammonium

First principle investigation of the linker length effects on the thermodynamics of divalent pseudorotaxanes

• Andreas J. Achazi,
• Doreen Mollenhauer and
• Beate Paulus

Beilstein J. Org. Chem. 2015, 11, 687–692, doi:10.3762/bjoc.11.78

• energies of association (Gibbs free (binding) energies) for divalent crown-8/ammonium pseudorotaxanes are determined by investigating the influence of different linkers onto the binding. Calculations are performed with density functional theory including dispersion corrections. The translational

• ; Gibbs energy; pseudorotaxanes; solvent effects; COSMO-RS; Introduction If two or more binding sites of a molecular system are involved in the association process, the interaction energy can be significantly increased compared to the sum of the individual binding energies. This effect is called

• contributions, enthalpic and entropic temperature effects as well as solvent effects are included in our simulations in order to compare to experimentally obtained Gibbs energy of association. Results and Discussion In order to investigate the cooperativity effects of the binding between divalent host molecules

Potential of acylated peptides to target the influenza A virus

• Daniel Lauster,
• Damian Pawolski,
• Julian Storm,
• Kai Ludwig,
• Rudolf Volkmer,
• Henry Memczak,
• Andreas Herrmann and
• Sumati Bhatia

Beilstein J. Org. Chem. 2015, 11, 589–595, doi:10.3762/bjoc.11.65

• have been partially neutralized by the liposomes, either by attachment and/or incorporation into the lipid bilayer. Very likely, in case of stearylated peptides, we surmise incorporation into the bilayer via the fatty acyl chain. To verify the association with lipid membranes exemplarily, we

• results show that acylated peptides, e.g., C18-PeBGF, could readily insert into biological membranes. As we observed association with the plasma membrane of red blood cells we surmise that those peptides could also insert into the virus envelope. Conclusion Here, we investigated the potential of a