One-pot synthesis of block-copolyrotaxanes through controlled rotaxa-polymerization

• Jessica Hilschmann,
• Gerhard Wenz and
• Gergely Kali

Beilstein J. Org. Chem. 2017, 13, 1310–1315, doi:10.3762/bjoc.13.127

• description see Supporting Information File 1). The eventual content of free RAMEB in the product was checked by isothermal calorimetry (ITC) and was around 3 wt %. The conversion of the monomers was calculated from the yield of polyrotaxane minus the total RAMEB content. In both cases, the monomer

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

• connection of one CD moiety at each phenylene unit. Based on the stiffness of the polymer chain self-passivation of CD polymer modified surfaces is reduced to a minimum. Furthermore, the ethynyl end groups are easily functionalized by click chemistry. Isothermal titration calorimetry (ITC), fluorescence

• hydrophilic guest to significantly improve the solubility in water. Binding constants of about 40,000 M−1, which were in the same range as literature values for the incorporation of adamantane derivatives into β-CD, [61] were obtained using ITC measurements considering a two-step sequential complexation with

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• two until we settled in. Although a much larger department than UNO, UT Austin had a poorer ratio of NMR instruments to students, and so we focused mostly on isothermal titration calorimetry (ITC) based research. There was the small matter of sneaking into a closed city and slipping under the radar of

• the National Guard to “steal” our own hosts, reagents, and ITC instruments; but that story is perhaps for another time. Back in Austin with everything we needed, we got down to some research… and of course filling out countless forms for insurance claims and requests for financial aid from the Federal

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

• isothermal titrimetry calorimetry, ITC [52][70], are frequently used in characterizing host–guest complexation. When viscosity changes occur because of host–guest complexation, rheology may be used to characterize such complexation [71]. Some examples of aqueous polymer systems characterized by these

• octamethylene-linked β-CD dimer c (Figure 10a, b and c) [78] and related β-CD [79][80] dimers in aqueous solution. It was determined from ITC experiments that while β-CD formed a 1:1 host–guest complex with adamantane carboxylate, only one annulus of the β-CD dimer b and β-CD dimer c complexed adamantane

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

• sample at least 100 particles were measured. Calorimetric analysis Calorimetric titrations were performed at 25 °C using a Microcal VP-ITC titration microcalorimeter. Sample solutions were prepared in Millipore water. NMR spectroscopy 1H NMR spectra was recorded on a Bruker 400 MHz NMR spectrometer. 1H

• titrations of a) CD-PEI (CD concentration of 0.088 mM, cell) with Ad-TEG (1.1 mM, burette) and b) Ad-TEG (1.1 mM, cell) with CD (10 mM; burette). H = host (CD from CD-PEI or native CD) and G = guest (Ad from Ad-TEG). Experimental binding curve (markers) and best fit to a 1:1 model (line). ITC titration of Fc

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• inhibitor Gleevec [53][54][55]. Reported by the Innovative Technology Centre (ITC) in 2010, this landmark synthesis was realised as a continuous process featuring an amide formation, a nucleophilic substitution and a Buchwald–Hartwig coupling as key synthesis steps performed in flow (Scheme 4). Further

• . As a consequence this approach is better suited to the rapid formation of small quantities of directly purified material for screening purposes but does not constitute a viable mode of performing direct large scale manufacture. In the same year the ITC also reported on their efforts towards the flow

• incorporated analysis technique. As the safe use of organometallic reagents has emerged as a key facet of flow chemical synthesis [58], the ITC reported on the design and implementation of a dual injection loop system that could deliver solutions of organometallic reagents (i.e., LiHMDS or n-BuLi) as a pseudo

Peptide–polymer ligands for a tandem WW-domain, an adaptive multivalent protein–protein interaction: lessons on the thermodynamic fitness of flexible ligands

• Katharina Koschek,
• Vedat Durmaz,
• Oxana Krylova,
• Marek Wieczorek,
• Shilpi Gupta,
• Martin Richter,
• Alexander Bujotzek,
• Christina Fischer,
• Rainer Haag,
• Christian Freund,
• Marcus Weber and
• Jörg Rademann

Beilstein J. Org. Chem. 2015, 11, 837–847, doi:10.3762/bjoc.11.93

• tandem WW-domain of formin-binding protein (FBP21). Polymer carriers were conjugated with 3–9 copies of the proline-rich decapeptide GPPPRGPPPR-NH2 (P1). Binding of the obtained peptide–polymer conjugates to the tandem WW-domain was investigated employing isothermal titration calorimetry (ITC) to

• multivalent peptide–polymer conjugate to the tandem WW domain Binding studies with peptide–polymer conjugates were conducted employing isothermal titration calorimetry (ITC). This method enables the determination of the binding affinity of the multivalent ligands and elucidates the composition of the free

• multivalency of binding and/or the degree of crosslinking. Thus, the method enables the identification of polymer–protein aggregates containing several polymers and proteins in a complex. No precipitation of the multicomponent aggregates that interfered with ITC measurements was observed during the experiments

Impact of multivalent charge presentation on peptide–nanoparticle aggregation

• Daniel Schöne,
• Boris Schade,
• Christoph Böttcher and
• Beate Koksch

Beilstein J. Org. Chem. 2015, 11, 792–803, doi:10.3762/bjoc.11.89

• with peptide concentration. Isothermal titration calorimetry (ITC) was used to determine the thermodynamic parameters as well as the binding constant for the assembly of Au/MUA nanoparticles (Table 1). By fitting with a one set of binding site mode the binding stoichiometry N, the binding constant KB

• have almost the same binding stoichiometry determined by ITC. This can be explained by considering the following points. Due to the fibril formation of R2A2, R2A3, and R2A4 Au/MUA nanoparticles interact with distinct positions on the surface of the peptide fiber. Cryo TEM images reveal, that an excess

• ) Cryo TEM images of 100 µM R2A2 and 0.4 µM Au/MUA nanoparticles at pH 9 at a defocus of −1.8 µM. Thermodynamic parameters for the aggregation of Au/MUA nanoparticles with peptides VW05, R2A2, R2A3, and R2A4 obtained by ITC. List of amino acid to arginine ratios for the sequences investigated here

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

• dealing with the daunting task to quantify the binding constants for the di- and tetravalent multiporphyrin complexes for example using isothermal calorimetry (ITC), in order to analyze the thermodynamics and kinetics of multivalent binding in these architectures in detail. In the future, we will continue

Exploring monovalent and multivalent peptides for the inhibition of FBP21-tWW

• Lisa Maria Henning,
• Sumati Bhatia,
• Miriam Bertazzon,
• Michaela Marczynke,
• Oliver Seitz,
• Rudolf Volkmer,
• Rainer Haag and
• Christian Freund

Beilstein J. Org. Chem. 2015, 11, 701–706, doi:10.3762/bjoc.11.80

• the interaction between hPG-peptide conjugate 2 and FBP21-tWW was measured by isothermal titration calorimetry (ITC) and compared to the KD of the interaction between the monovalent peptide and FBP21-tWW to analyze if multivalent display in form of the hPG-peptide conjugate 2 increases binding

• aromatic residue N-terminal to the polyproline stretch could also be observed. To define an optimized single monovalent binder, we analyzed the affinities for a selected set of ligands from this panel of sequences with regard to FBP21’s WW domains by ITC under the same conditions as were used for the phage

• highest frequency in the phage display experiment (RPPCGYPLP), did not show any binding to either WW domain in ITC experiments, possibly reflecting the potential of the cysteine residue to form an unspecific complex with glutathione-S-transferase. Similarly, the peptide RPPPPHFPQ could not be confirmed as

Properties of cationic monosubstituted tetraalkylammonium cyclodextrin derivatives – their stability, complexation ability in solution or when deposited on solid anionic surface

• Martin Popr,
• Sergey K. Filippov,
• Nikolai Matushkin,
• Juraj Dian and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2015, 11, 192–199, doi:10.3762/bjoc.11.20

• PEMPDA-β-CD in solution with a series of simple aromatic guests (salicylic acid, p-methoxyphenol and p-nitroaniline) were determined by isothermal titration calorimetry (ITC) and compared to the native β-CD. Permanently charged cationic CD derivatives were successfully deposited on the anionic solid

• guest molecules (salicylic acid – SAL, p-methoxyphenol – MEQ, p-nitroaniline – NIA) at three different pH values (2.50, 7.00, 10.00) (Scheme 2). The Ks values were obtained by isothermal titration microcalorimetry (ITC) [32][33], which was selected as the most suitable method for our purpose. Other

• methods were also tested, but their usability was found to be lower than ITC. For example 1H NMR spectroscopy [34] requires relatively high concentrations of the guest and host molecules, which are often impossible to achieve due to the poor solubility in aqueous media. Conventional UV–vis spectroscopy

Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers

• Thorbjørn Terndrup Nielsen,
• Catherine Amiel,
• Laurent Duroux,
• Kim Lambertsen Larsen,
• Lars Wagner Städe,
• Reinhard Wimmer and
• Véronique Wintgens

Beilstein J. Org. Chem. 2015, 11, 147–154, doi:10.3762/bjoc.11.14

• -cyclodextrin polymers. In aqueous solution nanoparticles were formed from association between the (S)-camptothecin–dextran polymers and the β-cyclodextrin polymers. Keywords: (S)-camptothecin; cyclodextrins; fluorescence; nanoparticles; ITC; Introduction Cancer remains to be the major cause of mortality in

• ). Binding properties and formation of nanoparticles The ability to form inclusion complexes with β-CD and β-CD-polymers was determined by isothermal titration calorimetry (ITC) and fluorescence spectroscopy. The β-CD polymer (D70HPβ-CD) had been prepared from a 70 kDa dextran backbone modified with 6

• formation is enthalpy driven in the case of D10GP-CPT1, but mainly entropy driven (|TΔS| > |ΔH|) in the case of D70GP-CPT2. This high positive entropy variation shows a cooperative inclusion of the polymers. No binding between native β-CD and D70GP-CPT2 could be measured by ITC. Figure 1 shows the heat flow

Synthesis and characterization of a new photoinduced switchable β-cyclodextrin dimer

• Florian Hamon,
• Claire Blaszkiewicz,
• Marie Buchotte,
• Estelle Banaszak-Léonard,
• Hervé Bricout,
• Sébastien Tilloy,
• Eric Monflier,
• Christine Cézard,
• Laurent Bouteiller,
• Christophe Len and
• Florence Djedaini-Pilard

Beilstein J. Org. Chem. 2014, 10, 2874–2885, doi:10.3762/bjoc.10.304

• . The photoinduced, switchable binding behavior of AZO-CDim 1 was evaluated by ITC, NMR and molecular modeling in the presence of a ditopic adamantyl guest. The results indicate that AZO-CDim 1 can form two different inclusion complexes with an adamantyl dimer depending on its photoinduced isomers. Both

• binding site of the ditopic guest ADAdim 4 and one binding site of a particular β-CD dimer, bearing a terephthalic acid linker, was independent of the number of binding sites, that is, no cooperative effect was observed and a supramolecular polymer was formed. ITC is one of the most interesting methods to

• , enthalpies of dilution of the monotopic hosts β-CD and β-CD-NH2, the ditopic host AZO-CDim 1 and the guest ADAdim 4 were measured in separate experiments to determine the maximum concentration to use for the ITC experiments. Enthalpies of dilution of β-CD and β-CD-NH2 were negligible over a broad

Improving ITC studies of cyclodextrin inclusion compounds by global analysis of conventional and non-conventional experiments

• Eléonore Bertaut and
• David Landy

Beilstein J. Org. Chem. 2014, 10, 2630–2641, doi:10.3762/bjoc.10.275

• techniques ranging from spectroscopy to chromatography and including calorimetrical tools [1][2][3][4]. Within this scope, isothermal titration calorimetry (ITC) is gaining more and more importance, as it allows a complete thermodynamic description of the inclusion phenomena (binding constant K, inclusion

• enthalpy ΔH, inclusion entropy ΔS, heat capacity variation ΔCp ) [5][6][7][8][9][10][11]. On a methodological point of view, most ITC studies are based on the classical titration protocol. While one partner of the studied phenomenon, called titrand, is placed inside the cell, the second partner, called

• titrant, is contained in the syringe of the ITC device. Each injection of one partner on the other induces the formation of supramolecules, thus releasing an amount of heat which is proportional to the binding enthalpy and to the amount of complexes formed during this addition. The binding isotherm is

Towards the sequence-specific multivalent molecular recognition of cyclodextrin oligomers

• Michael Kurlemann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 2428–2440, doi:10.3762/bjoc.10.253

• complementary and non-complementary strands modified with guest molecules and the investigation of their complexation behavior towards each other by isothermal titration calorimetry (ITC). As complementary binding motifs n-butyl and α-CD and adamantane and β-CD were selected. It was found that it is possible to

• towards α- and β-CD was investigated by ITC experiments. The structures of the host–guest complexes were elucidated by NMR spectroscopy. The 1-adamantane-functionalized serine 17 shows complexation of α- and β-CD, forming 1:1 complexes. In both cases the adamantane moiety binds into the CD cavity, which

• 10 equivalents of α-CD (Figure 6B and C). The interaction of 18 with β-CD cannot be quantified based on the ITC measurement with 1 mM of 18 and 10 mM of β-CD. Nevertheless, the NMR spectra of the 1:10 mixture of 18 and β-CD show small variations in the chemical shifts of the protons compared to the

Expeditive synthesis of trithiotriazine-cored glycoclusters and inhibition of Pseudomonas aeruginosa biofilm formation

• Meriem Smadhi,
• Sophie de Bentzmann,
• Anne Imberty,
• Marc Gingras,
• Raoudha Abderrahim and
• Peter G. Goekjian

Beilstein J. Org. Chem. 2014, 10, 1981–1990, doi:10.3762/bjoc.10.206

• . Both homo- and heterobifunctional ligands are obtained by a straightforward preparative route, as an innovative approach. Additionally, isothermal titration calorimetry (ITC) and dynamic light scattering (DLS) helped to better understand lectin–ligand interactions between lecA or lecB and these

• lecB were determined by isothermal titration calorimetry (ITC) by addition of the ligands to a solution of lectin (Figure 3). Dissociation constants (Kd) and thermodynamic parameters (ΔG, ΔH, −TΔS) are listed in Table 1, together with the experimental binding stoichiometry (n), defined as the number of

• cluster 17 containing two D-galactose and one D-glucose residues provided better ITC titration curves and more rational n values than the bis D-galactosyl monopropargyl cluster 16, which may reflect precipitation of the lectin-cluster complex during the ITC experiment in the latter case, based on the DLS

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• experimental conditions that often biased the intrinsic phenomena under investigations [29]. For instance, when evaluating thermodynamic parameters by isothermal calorimetry (ITC), scientists used either truncated versions of for instance, tetrameric lectins such as ConA, or diluted conditions to avoid

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• the parallel HisHis compared to the antiparallel HisHis [40]. Isothermal titration calorimetry (ITC) confirmed that the interaction of FITC-HisHis (mixture of isomers) and NANA is characterized by the same stoichiometry (1:2) and nearly the same binding constants (K1 = 163 M−1 and K2 = 5.36 × 103 M−1

• ) were obtained. ITC data are provided in Supporting Information File 1. These findings indicate that the introduction of the FITC label does not affect the formation of the synthetic lectin HisHis and its interaction with NANA. Since the mixture of isomers is much more easily synthesized than the

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• efficient use of space and the opportunity for a 24/7 working regime, the ability of digital cameras to provide real-time information on the state of a laboratory is particularly useful. When we established our Innovative Technology Centre (ITC) for advanced chemical synthesis in 2005, all of the fume-hoods

Influence of cyclodextrin on the solubility and the polymerization of (meth)acrylated Triton^® X-100

• Melanie Kemnitz and
• Helmut Ritter

Beilstein J. Org. Chem. 2012, 8, 2176–2183, doi:10.3762/bjoc.8.245

• -complex was monitored by viscosity measurements. Results and Discussion Complexation study of Triton® X-100 with RAMEB-CD The complexation behavior of Triton® X-100 (1) with RAMEB-CD was investigated by means of an ITC experiment (Supporting Information File 1, Figure S1). Assuming the sequential-binding

• experiments were performed on a VP-ITC MicroCalorimeter from MicroCal, Northampton MA, and were controlled by MicroCal VP viewer 2000 ITC software. Experiments were conducted at 25 °C. A 2.5 mM solution of RAMEB-CD was titrated against a 0.2 mM solution of Triton® X-100. Titration was carried out by 30

• injections of 5 × 1 μL, 5 × 2 μL, 5 × 5 μL, 15 × 15 μL with a spacing time of 180 s. The stirring speed was set to 300 min−1. In a separate experiment the heat of dilution was measured and was subtracted from the binding isotherm. The results were calculated with Origin 7.0 and the MicroCal LLC ITC software

Influence of intramolecular hydrogen bonds on the binding potential of methylated β-cyclodextrin derivatives

• Gerhard Wenz

Beilstein J. Org. Chem. 2012, 8, 1890–1895, doi:10.3762/bjoc.8.218

• regioselective methods. Binding free energies and binding enthalpies of these hosts towards 4-tert-butylbenzoate and adamantane-1-carboxylate were determined by isothermal titration microcalorimetry (ITC). It was found that methyl substituents at the secondary positions of β-CD lead to a tremendous reduction of

• these guests should sensitively respond to changes in the methylation pattern, because they fit tightly into the cavity of β-CD giving rise to high binding constants [26][27]. Binding data were measured by isothermal titration calorimetry (ITC) because it is known to be the most accurate method, and

• because it additionally yields binding enthalpies and entropies [31][32]. Results Since methylated β-CD derivatives 2–6 are highly water-soluble they are well suited for ITC. The ITC titration curves for all the β-CD derivatives 1–6 were exothermic and were in accordance with a 1:1 stoichiometry of the

Mannose-decorated cyclodextrin vesicles: The interplay of multivalency and surface density in lectin–carbohydrate recognition

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2012, 8, 1543–1551, doi:10.3762/bjoc.8.175

• functions to bind into the cavity of cyclodextrins, the synthesized guest molecules were investigated regarding their 1:1 complexation behavior towards β-cyclodextrin. Isothermal titration calorimetry (ITC) was carried out with β-cyclodextrin and each of the synthesized guest molecules 1–4. The

• literature [30]. Methods: Isothermal titration calorimetry (ITC) measurements were performed on a Nano-Isothermal Titration calorimeter III (model CSC 5300; Calorimetry Sciences Corporation, London, Utah, USA). All samples were measured in distilled water at 23 °C by using a stirring rate of 250 rpm. For

• –adamantane conjugates 1–4 and amphiphilic cyclodextrin 5. Integrated peak area (left) and raw titration curves (right) for the ITC measurements of 1–4 with β-CD. The concentrations used are listed in Table 1. Schematic presentation of the binding between β-cyclodextrin and (A) monovalent guest 1, (B

Impact of cyclodextrins on the behavior of amphiphilic ligands in aqueous organometallic catalysis

• Hervé Bricout,
• Estelle Léonard,
• Christophe Len,
• David Landy,
• Frédéric Hapiot and
• Eric Monflier

Beilstein J. Org. Chem. 2012, 8, 1479–1484, doi:10.3762/bjoc.8.167

• isothermal titration calorimetry (ITC), at a suitable RAME-β-CD/phosphane concentration ratio ensuring the absence of micelles during the whole experiment. Under these conditions, the values reflect the interaction between a single CD with a single phosphane only. A 1/1 stoichiometry was found whatever the

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

• pseudorotaxanes In order to determine the binding strengths quantitatively, NMR titrations, dilution experiments, and ITC experiments were attempted. The NMR titrations suffer from the fact that different conformations of the tertiary amide groups hamper an in-depth evaluation of the titration data. The diamide N

• -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

• quantitative study. Two problems need to be solved: On one hand, the solubility of the hosts needs to be increased such that a concentration range can be reached that enables us to obtain thermochemical data from ITC experiments. On the other hand, a more suitable binding moiety would be advantageous for use

Advances in synthetic approach to and antifungal activity of triazoles

• Kumari Shalini,
• Nitin Kumar,
• Sushma Drabu and
• Pramod Kumar Sharma

Beilstein J. Org. Chem. 2011, 7, 668–677, doi:10.3762/bjoc.7.79

• of the 14α-demethylase results in accumulation of sterols and causes permeability change and malfunction of membrane proteins. The ergosterol biosynthesis inhibitor pathway is shown in Figure 7 [43]. Classification of triazoles First generation of triazoles Fluconazole (FLC, 9) Itraconazole (ITC, 10