Local energy decomposition analysis of hydrogen-bonded dimers within a domain-based pair natural orbital coupled cluster study

• Ahmet Altun,
• Frank Neese and
• Giovanni Bistoni

Beilstein J. Org. Chem. 2018, 14, 919–929, doi:10.3762/bjoc.14.79

• the water dimer calculated previously at the CCSD(T)/CBS level (−5.01 kcal/mol [68]) agrees remarkably well with the present DLPNO-CCSD(T) result (ΔEe = −4.95 kcal/mol, Table 1). The accurate calculation of ZPE correction of H-bonded systems requires larger basis sets and the inclusion of anharmonic

• dimerization energies range from −4.51 kcal/mol (Conf1) to −3.52 kcal/mol (Conf3). Therefore, the conformers of both dimers lie within 2 kcal/mol. The inclusion of the ZPE correction to relative energies, which amounts up to 0.7 kcal/mol, makes the energetic separation between the conformers even smaller

• typically of the same order of the overall . Electron correlation also affects the energetic separation of various conformers. For example HF predicts a large energetic separation between Conf2 and Conf3 for both water and HF dimers (about 0.6 kcal/mol) whilst the inclusion of electron correlation makes

Crystal structure of the inclusion complex of cholesterol in β-cyclodextrin and molecular dynamics studies

• Elias Christoforides,
• Andreas Papaioannou and
• Kostas Bethanis

Beilstein J. Org. Chem. 2018, 14, 838–848, doi:10.3762/bjoc.14.69

• dairy products has been studied thoroughly in recent years. Although the physicochemical characterization of the inclusion compound of cholesterol in β-CD has been achieved by various methods, no crystal structure has been determined so far. We report here the crystal structure of the inclusion compound

• of cholesterol in β-CD. The inclusion complex crystallizes in the triclinic space group P1 forming head-to-head dimers which are stacked along the c-axis. One well-defined cholesterol molecule ‘axially’ encapsulated inside the β-CD dimer and 22 water molecules that stabilize the complexes in the

• inclusion compound remains very stable in aqueous solution at both temperatures. Keywords: beta-cyclodextrin; cholesterol; crystal structure; molecular dynamics; Introduction Cholesterol ((3β)-cholest-5-en-3-ol, CHL, Figure 1a) is a polycyclic steroid that is synthesized in mammalian cells and has a

An uracil-linked hydroxyflavone probe for the recognition of ATP

• Márton Bojtár,
• Péter Zoltán Janzsó-Berend,
• Dávid Mester,
• Dóra Hessz,
• Mihály Kállay,
• Miklós Kubinyi and
• István Bitter

Beilstein J. Org. Chem. 2018, 14, 747–755, doi:10.3762/bjoc.14.63

• that they form any type of inclusion complexes disturbing the recognition of ATP. Association constant determination The association constant has been obtained from the emission spectra using standard methods for non-linear curve fitting [65]. The best fit was obtained using 1:1 stoichiometry which

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• for continuous processing. The main issue that has to be solved in such set-up is the tolerability of the catalyst to water (its solubility, its activity, etc.) [55]. A strategy to overcome this problem is the inclusion and confinement of the homogeneous catalysts into a host nano-architecture [56

Terahertz spectroscopy of 2,4,6-trinitrotoluene molecular solids from first principles

• Ido Azuri,
• Anna Hirsch,
• Anthony M. Reilly,
• Alexandre Tkatchenko,
• Shai Kendler,
• Oded Hod and
• Leeor Kronik

Beilstein J. Org. Chem. 2018, 14, 381–388, doi:10.3762/bjoc.14.26

• a more severe challenge for the TS-vdW scheme used here. The computed spectra for the two TNT polymorphs, in the range from 0 to 3.3 THz, is given in Figure 2. Several interesting observations can be drawn from the figure. First, it is readily observed that inclusion of TS-vdW interactions improves

• have calculated terahertz spectra for the monoclinic and orthorhombic polymorphs of 2,4,6-TNT, using DFT both with and without Tkatchenko–Scheffler pair-wise dispersion interactions. We obtained very good agreement with experimental data upon inclusion of dispersion interactions, whereas lack of

• that modes in the range from 0 to ca. 3.3 THz bear contributions from both inter- and intramolecular vibrations, with the former dominating below ca. 1.5 THz and the latter primarily involving nitro and methyl groups. Finally, we showed that the theoretical results are little affected by the inclusion

Binding abilities of polyaminocyclodextrins: polarimetric investigations and biological assays

• Marco Russo,
• Daniele La Corte,
• Annalisa Pisciotta,
• Serena Riela,
• Rosa Alduina and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2751–2763, doi:10.3762/bjoc.13.271

• derivatives, obtained by anchoring suitable polyammonium or imidazolium pendant groups onto the main macrocycle scaffold [23][24][25][26][27][28]. The latter example is interesting, because of the well-known ability of these macrocycles to form inclusion complexes with diverse organic guest molecules [29][30

• knowledge, the possible inclusion of a generic guest/drug molecule into CD derivatives bearing amine groups have been studied only occasionally [41][43][44][45][46][47][48]. Moreover, the interaction of polycationic CDs with polynucleotides has been mainly considered by targeting their abilities in gene

• inclusion properties of the main CD scaffold. At the same time, we wanted to clarify the microscopic features and quantitative aspects of the interaction between AmCDs and polyanions such as polynucleotides. For these purposes, we investigated by means of polarimetry the behaviour of materials CD1–CD3

Binding abilities of a chiral calix[4]resorcinarene: a polarimetric investigation on a complex case of study

• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2698–2709, doi:10.3762/bjoc.13.268

• Polarimetry was used to investigate the binding abilities of a chiral calix[4]resorcinarene derivative, bearing L-proline subunits, towards a set of suitably selected organic guests. The simultaneous formation of 1:1 and 2:1 host–guest inclusion complexes was observed in several cases, depending on both the

• that the binding abilities of CAP−1 are modest. Significant inclusion is shown only by the large triphenylphosphonium cation 6, and by the neutral guests 8 and 10. In the former two cases, even the presence of 2:1 complexes can be detected. Polarimetric data for cations 9, 11 and 12 reveal a weak

• benzylammonium cation 7 forms 1:1 complexes only. In this case, K1 values decrease on increasing the average negative charge of the host (whereas CAP−1 does not include it, as we already mentioned). If Coulomb interactions were the main driving force for the inclusion process, then a regular increase of K1

Synthesis and supramolecular properties of regioisomers of mononaphthylallyl derivatives of γ-cyclodextrin

• Markéta Bláhová,
• Sergey K. Filippov,
• Lubomír Kováčik,
• Jiří Horský,
• Simona Hybelbauerová,
• Zdenka Syrová,
• Tomáš Křížek and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2017, 13, 2509–2520, doi:10.3762/bjoc.13.248

• reasons. Compared to α- or β-CD, the number of publications dealing with γ-CD is quite small, e.g., [14][15]. The naphthyl group is well known for its ability to make inclusion complexes with CDs [16]. The allyl connecting linker is relatively rigid and should support the formation of supramolecular

• the shape of peaks, but also in the value of the chemical shifts. For both regioisomers the concentration dependence of chemical shifts in aromatic and allyl areas indicates intermolecular association such as inclusion of the naphthylallyl moiety into the cavity of γ-CD or π stacking of naphthyls. The

• absence of the significant concentration dependence of chemical shifts of the CD hydrogens does not disqualify inclusion complexation because changes of chemical shifts by 0.01 ppm or less were observed upon inclusion of an aromatic guest into the γ-CD cavity [41]. To reconcile the absence of interactions

A permutation approach to the assignment of the configuration to diastereomeric tetrads by comparison of experimental and ab initio calculated differences in NMR data

• Przemysław J. Boratyński

Beilstein J. Org. Chem. 2017, 13, 2478–2485, doi:10.3762/bjoc.13.245

• capable software has led to inclusion of computational chemistry into the organic laboratory practice [2]. This provided a powerful tool to augment the interpretation of experimental data including NMR results [3][4][5][6][7][8][9][10]. Comparisons of experimental and theoretical spectra for the pairs of

• other hand RMS deviation and Pearson correlation coefficient proved as the most effective scores. While assignment for the three out of four diastereomers was found to be mostly accurate, synthesis and inclusion of a “missing” isomer would noticeably improve the chance for a correct assignment (100% vs

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• it was found that the inclusion of the additive TMS-morpholine [36][37] was also required to ensure a high diastereoisomeric excess of 38a. The epoxide 38a was then ring-opened using Et3N·3HF to deliver the difluorodiol 39a as a mixture of regioisomers. This mixture subsequently converged during the

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

• equivalent – methyl α-D-glucopyranoside – was investigated for a deeper understanding of the type of host–guest interactions. Solid state studies of PTX/CDs were performed using FTIR–ATR and Raman spectroscopy techniques. Keywords: antifolate; cyclodextrin; hydrophobic interactions; inclusion complexes

• various sizes (4.7–8.3 Å) into which distinct compounds may enter and form inclusion complexes, an ability that is thoroughly used by the pharmaceutical industry for the formation of drug delivery systems [1][2][3][4][5]. The formation of an inclusion complex often results in a favorable change of

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• = 2.7 kcal mol−1. The C···N bond distance is slightly shorter in 16b (2.673 Å) than in 16a (2.682 Å). Many attempts to locate a transition state structure for the C–N bond formation starting from either 16a or 16b failed. Even though the geometry optimizations were performed with implicit inclusion of

• . Transition state structures with combined implicit (SMD model) and explicit inclusion of the solvent were thus searched for. The geometry of 16a allowed the creation of a network of stabilizing interactions between an explicit methanol solvent molecule and both the N–H proton and the OMe group (N–H···O

Superstructures with cyclodextrins: Chemistry and applications IV

• Gerhard Wenz

Beilstein J. Org. Chem. 2017, 13, 2157–2159, doi:10.3762/bjoc.13.215

• repulsive. The first examples of superstructures formed by attractive intermolecular forces were complexes of crown ethers [1], cryptands [2] and spherands [3], which were recognized by the 1987 Nobel Prize in Chemistry. In addition, inclusion compounds of cyclodextrins (CDs), cyclic oligomers of glucose

Solid-state studies and antioxidant properties of the γ-cyclodextrin·fisetin inclusion compound

• Joana M. Pais,
• Maria João Barroca,
• Maria Paula M. Marques,
• Filipe A. Almeida Paz and
• Susana S. Braga

Beilstein J. Org. Chem. 2017, 13, 2138–2145, doi:10.3762/bjoc.13.212

• , neuroprotecting, and suppression or prevention of tumors. The present work describes the preparation of a water-soluble, solid inclusion compound of fisetin with gamma-cyclodextrin (γ-CD), a cyclic oligosaccharide approved for human consumption. A detailed physicochemical analysis of the product is carried out

• using elemental analysis, powder X-ray diffraction (PXRD), Raman, infrared and 13C{1H} CP-MAS NMR spectroscopies, and thermal analysis (TGA) to verify fisetin inclusion and to present a hypothetical structural arrangement for the host–guest units. The antioxidant activity of the γ-CD·fisetin inclusion

• are liposome derivatives) [20], and cyclodextrin inclusion complexes [21][22][23]. Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides produced by bacterial degradation of starch. Native CDs have six to eight α-D-glucose units linked by α-1,4 bonds, being called α-, β- and γ-CDs

Complexation of molecular clips containing fragments of diphenylglycoluril and benzocrown ethers with paraquat and its derivatives

• Leonid S. Kikot',
• Catherine Yu. Kulygina,
• Alexander Yu. Lyapunov,
• Svetlana V. Shishkina,
• Roman I. Zubatyuk,
• Tatiana Yu. Bogaschenko and
• Tatiana I. Kirichenko

Beilstein J. Org. Chem. 2017, 13, 2056–2067, doi:10.3762/bjoc.13.203

• its analogues 8–10 (Figure 1). Results and Discussion Complexation studies Paraquat (7) and its derivatives are among the most studied electron-acceptor guests that can form stable inclusion complexes with electron-donating molecules. Stabilization of such inclusion complexes is mainly realized due to

• π–π stacking and C–H∙∙∙X (X = N, O, F ...) interactions. The stability of inclusion complexes based on molecular clips and paraquat derivatives depends on two factors: 1) the value of the positive charge on the dipyridinium fragment of paraquat derivatives, the distribution of which is well

• observed for other complexes of the clips 1–5 with paraquat derivatives 8–10. This is typical for most pseudorotaxanes and catenanes and an evidence of the fairly stable host–guest inclusion complexes [33][34]. The ability of the obtained clips 1–5 to act as receptors for the guests 7–10 in solution was

Difunctionalization of alkenes with iodine and tert-butyl hydroperoxide (TBHP) at room temperature for the synthesis of 1-(tert-butylperoxy)-2-iodoethanes

• Hao Wang,
• Cui Chen,
• Weibing Liu and
• Zhibo Zhu

Beilstein J. Org. Chem. 2017, 13, 2023–2027, doi:10.3762/bjoc.13.200

• -vinylbenzene gave almost identical yields of the corresponding products. In addition, the inclusion of different R1 and R2 groups on styrenes, such as 1,1-disubstituted/1,2-disubstituted/1,1,2-trisubstituted alkenes (1-(prop-1-en-2-yl)benzene, 1-methyl-4-(prop-1-en-2-yl)benzene and 1,1-diphenylethene), had no

High-speed vibration-milling-promoted synthesis of symmetrical frameworks containing two or three pyrrole units

• Marco Leonardi,
• Mercedes Villacampa and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2017, 13, 1957–1962, doi:10.3762/bjoc.13.190

• hydrogen bonding, which would be disrupted in the alternative conditions involving the use of methanol as solvent. The scope of the method is summarized in Figure 1. In some cases (compounds 1a–g) the spacer was simply a polymethylene chain, but the inclusion of spacer chains containing an amino group (1h

Influence of the milling parameters on the nucleophilic substitution reaction of activated β-cyclodextrins

• László Jicsinszky,
• Kata Tuza,
• Giancarlo Cravotto,
• Andrea Porcheddu,
• Francesco Delogu and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 1893–1899, doi:10.3762/bjoc.13.184

• effect on the nucleophilic reaction. Keywords: cyclodextrins; milling parameters; nucleophilic substitution; planetary ball mill; Introduction Their hollow structures make cyclodextrins (CDs) a class of carbohydrates that can form inclusion complexes with organic molecules, inorganic salts and complex

• findings lend support to the idea that mechanical activation can induce chemical reactivity [29] and selectivity [30] which is different to that observed in solution, which can be further complicated by the inclusion complex formation property of cyclodextrins. How exactly the milling parameters influence

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

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

• structure; Introduction Cyclodextrins (CDs) are cyclic, water-soluble carbohydrates with a rather non-polar cavity that can host a variety of organic molecules (guests) and form inclusion complexes [1]. The guest molecules may be completely or partly enclosed inside the cavity depending on their size and

• the enhancement of solubility, bioavailability and stability of drugs [2][3][4][5]. Moreover, being oligomers of α-D-glucopyranose, CDs possess an intrinsic chirality, thus they form diastereomeric inclusion complexes with enantiomeric pairs and frequently they exhibit enantioselectivity in aqueous

• solution or they can co-precipitate with only one enantiomer (enantioseparation). The separation of enantiomers via cyclodextrin inclusion is particularly important in the case of guests of pharmaceutical interest, since enantiomerically pure drugs are crucial for the pharmaceutical industry [1][6][7]. It

Interactions between shape-persistent macromolecules as probed by AFM

• Johanna Blass,
• Jessica Brunke,
• Franziska Emmerich,
• Cédric Przybylski,
• Vasil M. Garamus,
• Artem Feoktystov,
• Roland Bennewitz,
• Gerhard Wenz and
• Marcel Albrecht

Beilstein J. Org. Chem. 2017, 13, 938–951, doi:10.3762/bjoc.13.95

• end groups were prepared starting from diacetylene-modified cyclodextrin monomers by a combined Glaser coupling/click chemistry approach. Structural perfection of the neutral CD polymers and inclusion complex formation with ditopic and monotopic guest molecules were proven by MALDI–TOF and UV–vis

• of the CD polymer and a reactive isothiocyanate–silane monolayer. Atomic force measurements of CD polymer decorated surfaces show enhanced supramolecular interaction energies which can be attributed to multiple inclusion complexes based on the rigidity of the polymer backbone and the regular

• configuration of the CD moieties. Depending on the geometrical configuration of attachment anisotropic adhesion characteristics of the polymer system can be distinguished between a peeling and a shearing mechanism. Keywords: AFM; cyclodextrin; inclusion complexes; molecular recognition; polyconjugated polymers

The effect of cyclodextrin complexation on the solubility and photostability of nerolidol as pure compound and as main constituent of cabreuva essential oil

• Joyce Azzi,
• Pierre-Edouard Danjou,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2017, 13, 835–844, doi:10.3762/bjoc.13.84

• solid complexes was assessed by HPLC. The structural characterization of CD/trans-Ner inclusion complex was then conducted by NMR spectroscopy followed by molecular modelling studies. The effect of encapsulation on the Ner photostability was also carried out over time under UVB irradiation. AL-type

• phase-solubility diagrams were obtained, suggesting the formation of 1:1 CD/Ner inclusion complexes. The solubility of Ner was enhanced by approximately 70-fold in the presence of 10 mM HP-β-CD. Moreover, high EE % values were obtained for 5:1 and 10:1 HP-β-CD:Ner molar ratios. NMR and molecular

• characteristic is their ability to form inclusion complexes with poorly soluble guest molecules which are entrapped in the hydrophobic cavity of CDs. Chemical modifications of the hydroxy groups of CDs can be performed to obtain water-soluble CD derivatives like hydroxypropyl-β-CD (HP-β-CD), methylated CDs

Cyclodextrins tethered with oligolactides – green synthesis and structural assessment

• Cristian Peptu,
• Mihaela Balan-Porcarasu,
• Alena Šišková,
• Ľudovít Škultéty and
• Jaroslav Mosnáček

Beilstein J. Org. Chem. 2017, 13, 779–792, doi:10.3762/bjoc.13.77

• polymers with different core and similar number of arms. The modification of CDs with a reduced amount of monomer units results in CD-oligomer materials which still keep an important property of the starting CDs, like their inclusion ability [16]. The CD-oligoester conjugate, compounds with a relatively

• The properties of cyclodextrin-oligoester covalent conjugates, situated at the border of low and high molecular weight compounds can be influenced by both the carbohydrate and the oligoester components. The properties of such materials like solubility, miscibility with other materials, inclusion

• homogenous product, with low polymerization degree, useful for preparation of inclusion complexes. However, for characterization purposes this sample fractionation is useful as long as both fractions are analyzed. MALDI spectra of F2 fractions (Figure 3) are clearly showing that the average number of monomer

Inclusion complexes of β-cyclodextrin with tricyclic drugs: an X-ray diffraction, NMR and molecular dynamics study

• Franca Castiglione,
• Fabio Ganazzoli,
• Luciana Malpezzi,
• Andrea Mele,
• Walter Panzeri and
• Giuseppina Raffaini

Beilstein J. Org. Chem. 2017, 13, 714–719, doi:10.3762/bjoc.13.70

• 7, 20131 Milano, Italy 10.3762/bjoc.13.70 Abstract Tricyclic fused-ring cyclobenzaprine (1) and amitriptyline (2) form 1:1 inclusion complexes with β-cyclodextrin (β-CD) in the solid state and in water solution. Rotating frame NOE experiments (ROESY) showed the same geometry of inclusion for both 1

• explicit water to study the inclusion complexes of two tricyclic aromatic molecules – cyclobenzaprine (1) and amitriptyline (2, Figure 1) – with β-cyclodextrin (β-CD). Previous work already considered certain aspects of the interaction of 2 with β-CD [3][4][5][6][7][8], but no full characterization of the

• complex geometry in solution and in the solid state was carried out, while the only similation study of this complex was very limited both in scope and in the adopted methodology [6]. In addition, to the best of our knowledge no study was ever performed on the inclusion complex of the strictly related

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• ) when compared to 36% release at pH 7 and 27% at pH 12. In order to improve the drug delivery profile of the complex, the authors developed a β-cyclodextrin/tetracycline (β-TC) host–guest inclusion complex, which allows a second “barrier” of release. The pre-formulated β-TC complex was loaded onto the