A conformationally adaptive macrocycle: conformational complexity and host–guest chemistry of zorb[4]arene

• Liu-Pan Yang,
• Song-Bo Lu,
• Arto Valkonen,
• Fangfang Pan,
• Kari Rissanen and
• Wei Jiang

Beilstein J. Org. Chem. 2018, 14, 1570–1577, doi:10.3762/bjoc.14.134

• −. NMR titrations and isothermal titration microcalorimetry (ITC) were then performed to obtain the association constants. For small guests such as 1+, 2+, 6+–9+, NMR titration experiments with ZB4 have been performed due to the fast equilibrium of the free and ZB4-complexed guests on the NMR time scale

A three-armed cryptand with triazine and pyridine units: synthesis, structure and complexation with polycyclic aromatic compounds

• Claudia Lar,
• Adrian Woiczechowski-Pop,
• Attila Bende,
• Ioana Georgeta Grosu,
• Natalia Miklášová,
• Elena Bogdan,
• Niculina Daniela Hădade,
• Anamaria Terec and
• Ion Grosu

Beilstein J. Org. Chem. 2018, 14, 1370–1377, doi:10.3762/bjoc.14.115

• pyrene, anthracene and 1,5-dihydroxynaphthalene as guest molecules was investigated by NMR titration experiments and molecular modelling. The spectra recorded during the NMR titrations of cryptand 2 with increasing amounts of the named guests (ratio 1:9 to 9:1), revealed only one set of signals. However

• the theoretical one. Global non-linear regression analysis of the 1H NMR titration data indicated the formation of 1:1 stoichiometric complexes. The association constants for the complexation of 2 with anthracene, pyrene and 1,5-dihydroxynaphthalene are 472.81 M−1 ± 4.9882, 55.22 M−1 ± 2.7771 and

• different host–guest complexations were −26.30 kcal/mol for cryptand–anthracene, −22.64 kcal/mol for cryptand–pyrene and −21.44 for cryptand–1,5-dihydroxynaphthalene cases, respectively. The higher values obtained by the NMR titration experiments for the complexation of the unsubstituted polyaromatic guests

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• equilibrium between mononucleotides and hairpins representing primer–template duplexes, as chosen for measuring dissociation constants by NMR titration. Template-directed primer extension on an RNA template performed with OAt-GMP at 1.8 mM (orange), 3.6 mM (blue), or 7.2 mM (green) initial concentration. a

Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands

• Nikolay V. Lukashev,
• Gennadii A. Grabovyi,
• Dmitry A. Erzunov,
• Alexey V. Kazantsev,
• Gennadij V. Latyshev,
• Alexei D. Averin and
• Irina P. Beletskaya.

Beilstein J. Org. Chem. 2017, 13, 564–570, doi:10.3762/bjoc.13.55

• [8]. However, we did not observe complexation of pincer ligands 5c–e with inorganic or organic anions by NMR titration. The attempt to increase the anion affinity for the ligands by exhaustive alkylation of amino groups with trimethyloxonium tetrafluorborate led exclusively to methylation of hydroxy

Spectral and DFT studies of anion bound organic receptors: Time dependent studies and logic gate applications

• Srikala Pangannaya,
• Neethu Padinchare Purayil,
• Shweta Dabhi,
• Venu Mankad,
• Prafulla K. Jha,
• Satyam Shinde and
• Darshak R. Trivedi

Beilstein J. Org. Chem. 2017, 13, 222–238, doi:10.3762/bjoc.13.25

• calculated rate constants reveal a higher order of reactivity for AcO− ions. The 1H NMR titration and TDDFT studies provide full support of the binding mechanism. The Hg2+ and F− ion sensing property of receptor R1 has been utilized to arrive at “AND” and “INHIBIT” molecular logic gate applications

• output, the signaling unit has been linked to a conjugated system possessing a hydroxy functionality which acts as binding site for anions. UV–vis, 1H NMR titration studies along with DFT studies of the receptors R1 and R2 would help to arrive at the binding mechanism. The presence of heteroatoms in the

• comparison with AcO− ion whose pKa value is 4.8. The time response of receptors R1 and R2 in the presence of AcO− ion is represented in Supporting Information File 1, Figures S17 and S18. The observed rate constants at different wavelengths for R1 and R2 are summarized in Table 2. 1H NMR titration studies To

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• binding with iodide. Both L5 and L6 were inhibited by the addition of tetrabutylammonium chloride, which reinforces the proposal that these salts act as HBDs. Interestingly, NMR titration studies revealed that L6 could form a supramolecular complex not only with a chloride anion, but also with chlorine

• establish that L13 forms weak 1:1 complexes with chloride and bromide anions. Thus, 1H NMR titration studies of L13 with R2 = C6F5 demonstrated the formation of the corresponding chloride complex with 1:1 stoichiometry and Ka ≈ 200 M−1. In light of the recent studies by Shirakawa and Maruoka [50][51], we

Synthesis and properties of fluorescent 4′-azulenyl-functionalized 2,2′:6′,2″-terpyridines

• Adrian E. Ion,
• Liliana Cristian,
• Mariana Voicescu,
• Masroor Bangesh,
• Augustin M. Madalan,
• Daniela Bala,
• Constantin Mihailciuc and
• Simona Nica

Beilstein J. Org. Chem. 2016, 12, 1812–1825, doi:10.3762/bjoc.12.171

• that a 2:1 complex is formed. The straight slope and its saturation at a ratio of 0.5 indicate a high binding constant which cannot be determined from this set of data. To assess the terpyridine-metal complex formation, 1H NMR titration of 4a with HgCl2 has been performed. The addition of 0.25

Amidofluorene-appended lower rim 1,3-diconjugate of calix[4]arene: synthesis, characterization and highly selective sensor for Cu²⁺

• Rahman Hosseinzadeh,
• Mohammad Nemati,
• Reza Zadmard and
• Maryam Mohadjerani

Beilstein J. Org. Chem. 2016, 12, 1749–1757, doi:10.3762/bjoc.12.163

• considerable fluorescence variations in comparison with L, and addition of Cu2+ ions to the corresponding solutions resulted in fluorescence quenching. Therefore, L can recognize Cu2+ even in the presence of other metal ions in acetonitrile solution. 1H NMR titration of L with Cu2+ In order to understand the

Creating molecular macrocycles for anion recognition

• Amar H. Flood

Beilstein J. Org. Chem. 2016, 12, 611–627, doi:10.3762/bjoc.12.60

• ion pairs (Kip). As a tribute to the four equilibria and the four species that are formed, the 1H NMR titration data for triazolophane 7 is exemplary (Figures 9b,c). Proton Ha reflects the 1:1 species by stopping its movements after 1 equiv of chloride is added. Protons Hh and Hi have inflection

• fitting of 1H NMR titration data. Both software have their limitations but their usage as tools to unravel complex equilibria is without parallel. Cooperativity of ion–pair complexation The most recent undertaking of ion pairing is to make it a feature and to examine, in glorious detail, how ion pairs can

• that dominate in dichloromethane for which the (b) propylene triazolophane’s (c) 1H NMR titration data is particularly reflective of the four-equilibrium model. (c) Adapted with permission from [14], copyright 2011 Wiley. Representations of (a) aryl–triazole–ether macrocycle 12 and (b) the ion-pair

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

• phenomenon in deep. In this study, inclusion complexes were characterized in terms of formation constants (Kf), complexation efficiency (CE), CD:guest molar ratio and increase in bulk formulation by using an UV–visible competitive method, phase solubility studies as well as 1H and DOSY 1H NMR titration

• method, phase solubility studies as well as 1H and DOSY 1H NMR titration experiments. An algorithmic treatment was applied to NMR results to calculate Kf values. This algorithm is the first attempt that associates numerous signals (chemical shifts and diffusions coefficients variations) from several

• structure of inclusion complexes [42]. The protons of 1 and 2 are named according to Figure 1. 1H and DOSY 1H NMR titration experiments Generally, hydrogen atoms of CD and guest are affected by the inclusion resulting in a displacement of their chemical shifts (δ) and diffusion coefficients (D). 1H and DOSY

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

• deeper insights into the interactions between L1 or L2 and fluoride, 1H NMR titration experiments were performed in DMSO-d6 (Figure 8 and Figure S9 in Supporting Information File 1). The measurements indicate that the N–H peak disappears after addition of one equivalent of TBAF while the other aromatic

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

• solution, because we already know from NMR titration studies that the [5]pseudorotaxane A14@C4 is the predominant species in solution (Figure 4b). To summarize, all four desired [3]- or [5]pseudorotaxanes could be detected by mass spectrometry despite the likeliness of A12@C2 and A14@C4 to dissociate upon

• complementary di- and tetravalent hosts C2 and C4 could be achieved. All four molecules show strong binding even to simple monovalent building blocks A1 and C1, respectively, which could be shown by NMR-titration experiments as well as mass spectrometry. Furthermore, the formation of the di- and tetravalent

• pseudorotaxanes A2@C2, A22@C4, A4@C22, and A4@C4 could be demonstrated qualitatively by NMR spectroscopy and was investigated in detail by mass spectrometry. Since the association constants in the monovalent cases are already too high to be determined by NMR-titration experiments, currently ongoing work is

Structure elucidation of β-cyclodextrin–xylazine complex by a combination of quantitative ¹H–¹H ROESY and molecular dynamics studies

• Syed Mashhood Ali,
• Kehkeshan Fatma and
• Snehal Dhokale

Beilstein J. Org. Chem. 2013, 9, 1917–1924, doi:10.3762/bjoc.9.226

• stoichiometry and binding constant of host–guest complexes, 1H NMR titration experiments are most common. These titration experiments give Δδ data for many independent signals which can independently be used to determine the stoichiometry and binding constant. Several NMR versions of Benesi–Hildebrand equations

Synthesis and anion recognition properties of shape-persistent binaphthyl-containing chiral macrocyclic amides

• Marco Caricato,
• Nerea Jordana Leza,
• Claudia Gargiulli,
• Giuseppe Gattuso,
• Daniele Dondi and
• Dario Pasini

Beilstein J. Org. Chem. 2012, 8, 967–976, doi:10.3762/bjoc.8.109

• , this recognition mechanism in 10 and 11 is suppressed and alternative mechanisms take place (see below). Complexation studies 1H NMR titration experiments showed that the addition of anionic guests, in the form of their tetrabutylammonium salts, produced progressive chemical-shift variations, along

• spectra were recorded at 500 MHz and at 298 K. Ka values for the complexation of (R,R)-12 with (n-Bu4N+)2X2− (X2− = −O2C(CH2)2CO2−, −O2C(CH2)3CO2−) were assessed by nonlinear treatment of the data obtained from 1H NMR titration experiments. Samples were prepared by adding to a 0.5 mL solution of the host

A ferrocene redox-active triazolium macrocycle that binds and senses chloride

• Nicholas G. White and
• Paul D. Beer

Beilstein J. Org. Chem. 2012, 8, 246–252, doi:10.3762/bjoc.8.25

• state by X-ray crystallography. Alkylation gives the corresponding triazolium macrocycle, which binds chloride and benzoate strongly in CD3CN solution through favourable charge-assisted C–H···anion interactions, as evidenced by 1H NMR titration experiments. Preliminary electrochemical studies reveal

• triazole N-acceptors on adjacent molecules. Anion-binding investigations The anion-binding properties of 5·2PF6 were investigated in CD3CN solution by 1H NMR titration experiments. Aliquots of anions as their N-tetrabutylammonium (TBA) salts were added to 5·2PF6 and the chemical shift of the (chemically

• demonstrated by 1H NMR titration experiments to bind chloride and benzoate in CD3CN, solely through charge-assisted C–H···anion hydrogen-bonding interactions. The redox-active macrocycle was also shown to sense chloride electrochemically via a cathodic shift of the Epa wave of the ferrocene/ferrocenium redox

Synthesis of multivalent host and guest molecules for the construction of multithreaded diamide pseudorotaxanes

• Nora L. Löw,
• Egor V. Dzyuba,
• Boris Brusilowskij,
• Lena Kaufmann,
• Elisa Franzmann,
• Wolfgang Maison,
• Emily Brandt,
• Daniel Aicher,
• Arno Wiehe and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2012, 8, 234–245, doi:10.3762/bjoc.8.24

• quite rigid connections between linker and binding sites. Although a quantitative assessment of binding strengths was not possible by NMR titration experiments, typical and significant shifts of the signals of the diamide moiety indicate qualitatively the formation of pseudorotaxanes from the axle and

• -CH3 and N-CH2 protons appear with four sets of signals, one for the (trans,trans)-, two for the asymmetric (trans,cis)- and one for the (cis,cis)-isomer. This, and significant signal overlaps, make it impossible to quantify the NMR titration data. For ITC measurements, the concentration range in which

Thermodynamic and kinetic stabilization of divanadate in the monovanadate/divanadate equilibrium using a Zn-cyclene derivative: Towards a simple ATP synthase model

• Hanno Sell,
• Anika Gehl,
• Frank D. Sönnichsen and
• Rainer Herges

Beilstein J. Org. Chem. 2012, 8, 81–89, doi:10.3762/bjoc.8.8

• thermodynamically as shown by NMR titration. Moreover, EXSY NMR experiments reveal that the vanadate dimer is also kinetically stabilized with respect to hydrolysis by complexation with Zn-cyclene. Keywords: EXSY NMR; NMR titration; supramolecular chemistry; vanadate condensation; 51V NMR; Zn-cyclene

• . The 51V NMR titration at pH 9.5 is shown in Figure 3 (for the corresponding spectra recorded at pH 7.6 and 8.5 see Supporting Information File 1). The addition of Zn-benzylcyclene 1 leads to an upfield shift of the monovanadate and the divanadate signal at all pH values that were investigated. This

• given in Å. Metal coordination as well as H–bond formation are operative in binding the oxo-anion to the zinc cyclene unit. The schematic representation (right) is used to improve clarity. 51V NMR titration at pH 9.5 ([V]t = 1.5 mM, [1]t = 0 to 7.5 mM (0 to 5 equiv), 100 mM CHES). [V]t and [1]t are the

Binding of group 15 and group 16 oxides by a concave host containing an isophthalamide unit

• Jens Eckelmann,
• Vittorio Saggiomo,
• Svenja Fischmann and
• Ulrich Lüning

Beilstein J. Org. Chem. 2012, 8, 11–17, doi:10.3762/bjoc.8.2

• halide anions. A general method for a quick estimation of the strength of binding derived from only a few data points is presented and gives an estimated Kass of pyridine-N-oxide of ca. 40 M−1, NMR titration confirms 25 M−1. Keywords: anion binding; association constant; estimation of binding constants

• constants were identified. Estimation rather than an exact determination of Kass would be fair enough. Once a good candidate is recognized, a standard determination of the association constant, for example, by NMR titration, can be done. With Δδmax unknown, the magnitude of the CIS cannot distinguish

• Supporting Information File 1, page S12), Kass for the best binder to 1, pyridine-N-oxide (PyNO), was estimated to be ca. 40 M−1. A subsequent NMR titration of host 1 with PyNO provided an association constant of 25 M−1 (see Supporting Information File 1). Remarkably, chloride ions are only very weakly bound

NMR studies of anion-induced conformational changes in diindolylureas and diindolylthioureas

• Damjan Makuc,
• Jennifer R. Hiscock,
• Mark E. Light,
• Philip A. Gale and
• Janez Plavec

Beilstein J. Org. Chem. 2011, 7, 1205–1214, doi:10.3762/bjoc.7.140

• mode for the 3·AcO− 1:1 complex. Stability constants of compound 1 measured in DMSO-d6/0.5% water, DMSO-d6/10% water and DMSO-d6/25% water and compound 2 in DMSO-d6/0.5% water at 298 K by 1H NMR titration techniques [37]. Selected 1H and 15N NMR chemical shifts for 1–4 (in ppm).a Selected NOE

A new fluorescent chemosensor for fluoride anion based on a pyrrole–isoxazole derivative

• Zhipei Yang,
• Kai Zhang,
• Fangbin Gong,
• Shayu Li,
• Jun Chen,
• Jin Shi Ma,
• Lyubov N. Sobenina,
• Albina I. Mikhaleva,
• Guoqiang Yang and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2011, 7, 46–52, doi:10.3762/bjoc.7.8

• emission spectra upon the addition of F−, resulting in highly selectivity for fluoride detection over other anions, such as Cl−, Br−, I−, HSO4−, H2PO4− and AcO− in CH3CN. 1H NMR titration, time-dependent density functional theory (TDDFT) calculations and other experiments confirm that the sensing process

• recognize fluoride anion (F−) with high selectivity and sensitivity over other anions (Cl−, Br−, I−, HSO4−, H2PO4− and AcO−). Both 1H NMR titration experiments and time-dependent density functional theory (TDDFT) calculations demonstrated that the mechanism is deprotonation of the pyrrole-NH. Results and

• −. 1H NMR titration 1H NMR titration was also carried out to confirm the deprotonation of receptor 1 by F−. Figure 9 shows the series of 1H NMR spectra of 1 upon the addition of increasing amounts of TBAF in DMSO-d6. As discussed above, HF2− anion was formed when the receptor was deprotonated by F− via

Preparation, structures and preliminary host–guest studies of fluorinated syn-bis-quinoxaline molecular tweezers

• Markus Etzkorn,
• Jacob C. Timmerman,
• Matthew D. Brooker,
• Xin Yu and
• Michael Gerken

Beilstein J. Org. Chem. 2010, 6, No. 39, doi:10.3762/bjoc.6.39

• –c, depicting the inversion of the electrostatic potential in the pincer subunits upon increasing the degree of fluorination. NMR titration experiments with electron-rich arenes (1,4-dimethoxybenzene, 1,3,5-trimethoxybenzene, N,N-dimethylaniline, N,N,N′,N′-tetramethyl-p-phenylenediamine) were carried

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

• ion binding processes are direct absorption and emission measurements utilizing chromophores in the receptor or analyte molecule, displacement assays with suitable dyes, NMR titration experiments, isothermal titration calorimetry and transport through an organic phase monitored by HPLC, NMR [37][38

• and (S)-1-methyl-1,2-propanediol for the enantiomeric recognition of amino acid ester derivatives [161]. The four similar macrocycles have been shown to be complexing agents for primary organic ammonium salts by 1H NMR titration. The best example, the depicted host 29, exhibited enantioselective

• showed a considerable binding affinity and enantiomeric discrimination of aromatic amine salts [162]. The binding properties were evaluated by 1H NMR titration in acetonitrile. For the (R,R)- and (S,S)-configurated host with a phenyl residue, the highest differences in the Kass values were observed: (R

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• phosphate were obtained from NMR titration experiments for both series of glucooligomers. The binding affinity of the thiourea and guanidine oligomers was stronger than in the case of the urea analogues. Stimulated by the interesting supramolecular properties and applications of cyclodextrins (CDs), a range

• and evaluated as phosphate binders in water (Figure 20) [76]. Association constants (Kas) for binding with dimethyl and phenyl phosphate were obtained from NMR titration experiments for both compounds. The results indicated that the binding strength depends strongly on the acidity of the NH protons

Synthesis of indolo[3,2-b]carbazole-based new colorimetric receptor for anions: A unique color change for fluoride ions

• Ajit Kumar Mahapatra,
• Giridhari Hazra and
• Prithidipa Sahoo

Beilstein J. Org. Chem. 2010, 6, No. 12, doi:10.3762/bjoc.6.12

• ), and not hydrogen bonding to it, is responsible for the drastic color change [47], as a result of a change in the optical properties of chromogenic indolocarbazole skeleton. This is in agreement with the NMR titration data. Such deprotonation was related to the acidity of the H-bond donor site and the

Size selective recognition of small esters by a negative allosteric hemicarcerand

• Holger Staats and
• Arne Lützen

Beilstein J. Org. Chem. 2010, 6, No. 10, doi:10.3762/bjoc.6.10

• esters 5–7, however, did not result in any significant shifts indicating size-selective discrimination of the different esters. In order to evaluate this phenomenon further we performed an NMR titration to determine the association constant for the binding of the arguably best guest ethyl acetate

• as the internal standard. Analysis of the binding isotherms obtained from the NMR titration experiments was done by non-linear regression methods. Qualitative binding studies of 2 and the model substrates 3–7. 1H NMR spectra (500.1 MHz, 298 K in mesitylene-d12, c0(2) = 5 mmol/L) of a) 2, b) 2 and 15

• equiv of 3, c) 2 and 15 equiv of 4, d) 2 and 15 equiv of 5, e) 2 and 15 equiv of 6, f) 2 and 15 equiv of 7. Marked in red rectangles are the regions of the signals of the acetal and some of the bipyridine hydrogen atoms of 2. 1H NMR titration (500.1 MHz, 298 K, c0(2) = 5.3 mmol/L) of 2 with increasing