Self-assembly of tris(2-ureidobenzyl)amines: a new type of capped, capsule-like dimeric aggregates derived from a highly flexible skeleton

A set of tris(2-ureidobenzyl)amines 3 was prepared and their dimerization processes thoroughly investigated. In spite of their inherent flexibility, tris(ureas) 3 form dimeric aggregates both in the solid state and in solution. Evidence for the existence of these dimeric species was provided by a combination of techniques (X-ray analysis, NMR and IR spectroscopy, and ESI-MS). The association constants and thermodynamic parameters for the dimerization processes of selected tris(ureas) were determined and show that they are enthalpically driven. Heterodimerization experiments in solution reveal a high degree of self-recognition or narcissistic self-sorting. On the other hand, desymmetrized tris(ureas) derived from 3 self-assemble with modest regioselectivities depending on the terminal substituent of every urea functionality.     

Spectroscopic characterisation of the inclusion complexes between the antifungal drugs naftifine and terbinafine and cyclodextrins

The complexation of naftifine (NF) and terbinafine (TB) with cyclodextrins (CDs) has been investigated by UV/visible and ¹H NMR spectroscopy, ROESY techniques and also ESI-MS. Both drugs form 1:1 inclusion complexes with all the CDs tested except with α-CD, as deduced from the Benesi–Hildebrand plots and confirmed by ESI-MS and NMR spectroscopy (Job plot method). The K ₁₁ values for NF decrease in the order β-CD > methylated β-CD > 2-hydroxypropyl-β-CD >γ-CD. The determination of the enthalpy and entropy provides information about the main driving forces in the process. The stability constants of the complexes NF–β-CD, TB–β-CD and TB–γ-CD determined by ¹H NMR spectroscopy are in agreement with the values obtained by UV. For TB–β-CD, the value is higher, due to the fact that the length of the TB aliphatic chain allows a deeper inclusion of the naphthalene group inside the corresponding β-CD molecule, according to the 2D ROESY experiments.     

New approach to IR study of monomer-dimer self-association: 2,2-dimethyl-3-ethyl-3-pentanol in tetrachloroethylene as an example

The dimerization of 2,2-dimethyl-3-ethyl-3-pentanol in tetrachloroethylene in the diluted region has been studied at four temperatures by IR spectroscopy. The aforementioned solute compound is chosen because self-association beyond dimerization is hampered by the steric hindrance generated by the bulky sidechains. The integrated absorbances of the monomer bands were treated based on Eq. (9) to obtain its molar absorptivity and dimerization constant. The same dimerization constant as well as the molar absorptivity of dimer band can be obtained based on Eq. (13) from the data treatment of the integrated absorbances of the dimer band. The disparity between two values of dimerization constant determined by two independent sources offers an opportunity to check the consistency of the determination. The standard enthalpy and entropy of dimerization have also been calculated by means of van't Hoff plot, respectively, from the data of temperature-dependent dimerization constants obtained from the monomer bands and dimer bands.     

Studies of the electrochemical reduction of some dinitroaromatics

The electrochemical reduction of a series of dinitroaromatics, along with one trinitro compound, has been investigated at a glassy carbon electrode in N,N-dimethylformamide. The separation between the two standard potentials for the reduction, E°₁ − E°₂, has been determined and discussed in terms of the structures of the compounds. cis-4,4′-Dinitrostilbene was shown to undergo redox-catalyzed isomerization to the trans isomer. This was demonstrated with partial controlled potential electrolysis followed by chromatographic analysis of the solution. It was also found that redox-catalyzed isomerization could adequately account for the voltammetric behavior. The anion radicals of 3,5-dinitropyridine and 1,3,5-trinitrobenzene undergo reversible dimerization reactions. The rate and equilibrium constants for the dimerization were determined by simulation of the voltammograms of these two compounds and also by simulation of the voltammograms obtained with solutions from the one-electron controlled potential reduction, that is, solutions of the dimer. The equilibrium constants for dimerization were also determined by electron paramagnetic resonance spectroscopy.     

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The dimerization of bis(4-methylphenyl)acetylene and of 1-(4′-methylphenyl)-2-phenylacetylene yields in each case an active dilithium compound which reacts with dichlorodiphenylsilane and leads to the corresponding silacyclopentadiene.UV and IR spectra of these derivatives are presented. It has been demonstrated by NMR spectroscopy that the compound bearing two phenyl and two 4-methylphenyl substituents on the silacyclopentadiene ring contains several isomers, which result from the position of the aryl substituents. Three isomers are present according to NMR spectra and the proportion of each is determined.     

Hydrogen bonding between nucleic acid constituents and amino acid amide group

The formation of hydrogen-bonded complexes between 9-ethyladenine and acetamide in chloroform solution has been studied by infrared spectroscopy. Comparison of the mixed solution spectra with the sum of the spectra of the separate monomers in solution shows that cyclic heterodimers are formed when acetamide binds to adenine base. Information is also obtained about the atomic arrangement of these heterodimers, where acetamide is bound to adenine base predominantly through the pyrimidine ring. Hydrogen bonds of this nature have been also observed for concentrated aqueous solutions of adenosine 5′-monophosphate in the presence of acetamide using Raman spectroscopy.     

Potentiometric, luminescence and NMR study of the interaction of Eu with glyceryl phosphates

Complexation of europium(III) with glyceryl-1- and -2-phosphates has been studied by metal ion luminescence, ¹H and ¹³C NMR spectroscopy and potentiometry. From the luminescence and NMR studies, the formation of a 1:1 inner-sphere complex, in which the glyceryl phosphate is directly bound to the metal, is confirmed. Similar apparent binding constants at pH 2 were obtained by the three methods. Values obtained by NMR at pH 2 are 53 M⁻¹ and 12 M⁻¹ for glyceryl-1- and -2-phosphate, respectively. By comparison with literature data on related systems it is suggested that the ligands bind through the phosphate group. To obtain structural information from the NMR data, complexation has also been studied with the lanthanide ions Dy(III), Er(III) and Gd(III) using both chemical shift and relaxation data. From this, metal-proton distance ratios have been calculated. Comparison of ¹H and ¹³C NMR spectral data in the presence of paramagnetic lanthanides suggests conformational equilibria in the solutions. From the potentiometric studies, global formation constants have been determined, and speciation diagrams obtained over the pH range 1.5pH7.0 for ligand/metal ratios of 1 and 30. Implications of these results on lanthanide induced fusion of phospholipid membranes are discussed.     

Determination of the structural arrangements of ketene oligomers using NMR, FT-IR and ESI-MS

Oligomer of ketene was synthesized using glycine as the source material in presence of free electron rich carbon through free radical mechanism. The structure and the compositions were determined by using ¹³C{¹H} NMR and DEPT – 135 spectroscopy measurements. Two-dimensional heteronuclear (HETCOR) NMR spectroscopy was used to resolve the ¹H NMR spectrum of the polymer. The NMR spectra reveal that the oligomers were generated as oligoester (OE), oligoketene (OK) and oligoacetal (OA) structural units. ESI-MS and ATR-FTIR also support these types of structural units in the crude polymer.     

Thermodynamic study of the dimerization of 8-anilino-1-naphthalenesulfonic acid by isothermal titration calorimetry

Dimerization of the fluorescence probe, 8-anilino-1-naphthalenesulfonic acid (ANS) in aqueous media have been studied by isothermal titration calorimetry (ITC). ITC experiments carried out at different pHs show that dimerization constants are highly pH dependent, decreasing their values with increasing pH. No dimerization is detected over pH 7. Analyzing the dependence of K_dim on pH, using a model that only considers dimers between zwitterionic molecules of ANS, a value of 5.6 for the pK of anilinium moiety is obtained. It is in agreement with the pK determined spectrophotometrically. The dimerization process is enthalpically disfavored and entropically driven at all pH and temperatures studied, indicating that hydrophobic effect has an important role on the formation of dimers. Although dimerization constants are low, dimerization equilibria must be taken into account when the energetics of the interaction of ANS to a protein is studied at pH below 7.     

温度对4-甲基丙烯酸2,2,6,6-四甲基哌啶醇酯与苯乙烯自由基共聚活性的影响

本文研究了4-甲基丙烯酸2,2,6,6-四甲基哌啶醇酯和苯乙烯在不同温度下的自由基共聚合反应。发现在石油醚、苯和二甲基甲酰胺等溶剂中,反应温度对共聚活性的影响不同。用NMR法测定了单体与溶剂的络合常数;计算了单体与溶剂相互作用的活化能和活化熵,依此对共聚活性与温度之间的关系进行了讨论。     

Self-assembly of achiral and chiral macrocyclic ligands: synthesis,protonation constants,conformation and asymmetric catalysis

New 30-membered achiral and chiral polyaza macrocyclic ligands, L1 and L2 were synthesized directly from [3 + 3] condensation of phthalic dicarboxaldehyde with cis- and (1R,2R)-diaminocyclohexane, respectively. The trimeric macrocyclic structures were confirmed by electrospray ionization mass spectrometry (ESI-MS), 1H NMR, 13C NMR spectroscopy and elemental analysis. Potentiometry was used to determine the protonation constants of the ligands. UV-vis spectrophotometric titration was employed to investigate the coordination and conformational properties of the chiral ligand (L2). Direct enantioselective aldol reaction has been successfully performed using 4-nitrobenzaldehyde and acetone in the presence of the chiral macrocycle and its zinc(II) complexes as catalysts.     

Melamine–formaldehyde resins: Molecular species distributions of methylolmelamines and some kinetics of methylolation

The addition reaction between melamine and formaldehyde has been studied by the direct observation with NMR spectroscopy and high-speed liquid chromatography. All of the nine methylolmelamines, including two isomers of di-, tri- and tetramethylolmelamine could be assigned. The liquid-chromatographic technique was applied to the quantitative analysis of methylolmelamines and the free formaldehyde contents in the reaction mixtures, and the molecular species distributions were determined. By using these quantitative methods, the equilibrium constants and rate constants for the individual reversible reactions were estimated.     

Spectrophotometric and thermodynamic study on the dimerization equilibrium of ionic dyes in water by chemometrics method

The monomer-dimer equilibrium and thermodynamic of several ionic dyes (Neutral Red, Nile Blue A, Safranine T and Thionine) has been investigated by means of spectrophotometric and chemometrics methods. The dimerization constants of these ionic dyes have been determined by studying the dependence of their absorption spectra on the temperature in the range 20-75 degrees C at concentrations of Neutral Red (1.73 x 10(-5) M), Nile Blue A (3.94 x 10(-5) M), Safranine (6.59 x 10(-5) M) and Thionine (6.60 x 10(-5) M). The monomer-dimer equilibrium of these dyes has been determined by chemometrics refinement of the absorption spectra obtained by thermometric titrations performed. The processing of the data carried out for quantitative analysis of undefined mixtures, based on simultaneous resolution of the overlapping bands in the whole set of absorption spectra. The enthalpy and entropy of the dimerization reactions were determined from the dependence of the equilibrium constants to the temperature (van't Hoff equation).     

Preferred dimerization of tetra-tolyl- and tetra-tosylurea derivatives of flexible and rigidified calix[4]arenes

The dimerization of tetratolyl- and tetratosyl-urea derivatives 1 and 2, derived from a tetrapentoxy calix[4]arene in the cone conformation and of the corresponding tetra-urea derivatives 3 and 4, in which the cone conformation is rigidified by the two crown-3 tethers, have been studied. All six possible equimolar mixtures were examined by 1H NMR using CDCl3 and CD2Cl2 as solvents. While no heterodimers are found for the combinations 1/3 and 2/4 in either solvent, all remaining combinations lead to the (exclusive) formation of heterodimers in CD2Cl2. In CDCl3 heterodimers are only observed for the combinations of 3 with 2 or 4. These results are discussed in terms of entropic and enthalpic contributions and compared with MD-simulations in a box of chloroform solvent molecules.     

Cu2+ and AMP complexation of enlarged tripodal polyamines

The synthesis, characterization, Cu2+ coordination and interaction with AMP of three tripodal polyamines are reported. The polyamines are based on the structure of the tetraamine (tren) which has been enlarged with three propylamino functionalities (), with a further anthrylmethyl fragment at one of its terminal primary nitrogens () or with naphthylmethyl fragments at its three ends (). The protonation constants of all three polyamines show that at pH 6, all six primary and secondary nitrogen atoms in the arms are protonated. The interaction with Cu2+ and AMP (adenosine-5'-monophosphate) has been studied by potentiometric, UV-Vis, ESI-MS spectroscopy and NMR techniques. pH-Metric, NMR and ESI/MS techniques indicate that and form with AMP adducts of 1:1, 2:1 and 3:1 AMP:L stoichiometries in water. This is one of the first examples for the formation of such complexes in aqueous solution. Formation of ternary complexes between , , , Cu2+ and AMP is observed. Paramagnetic NMR techniques have been used to obtain structural information on the binding mode of AMP to the Cu2+- binuclear complexes.     

Ureidopyrimidinones incorporating a functionalizable p-aminophenyl electron-donating group at C-6

[structure: see text] 2-Ureido-4-[1H]-pyrimidinones have been reported to dimerize via quadruple hydrogen bonding systems with dimerization constants >10(6) M(-1) in CDCl3. The dimerization constant, K(dim), is dependent on the solvent as well as the ring-substituents present, where previously alkyl (e.g., R1 = Me) and aromatic moieties (e.g., R1 = p-NO2C6H4, R1 = C6H2(OC13H27)3) have been incorporated at the C-6 position. To assess the influence of alternative, functionalizable, electron-donating groups on the dimerization motif and tautomeric distribution of isomers, the synthesis of compounds possessing aminophenyl functionality at the C-6 position has been achieved. NMR spectroscopy chemical shift analysis revealed that compound 2 (R1 = p-NH2C6H4, R2 = C6H13) existed as the 2-ureido-4-pyrimidinol dimeric DADA array in DMSO-d6, where a dimerization constant of 46 M(-1) was determined. This is the first time that a ureidopyrimidinone quadruple hydrogen bonding DADA array has been observed in pure DMSO, a highly polar solvent. The azo-derivative 5 of compound 2 was prepared which also adopted the pyrimidin-4-ol form in DMSO-d6. Compounds 7, 10 and 11 were then synthesized containing a more hydrophilic PEG unit in the lateral chain and the tautomeric distributions were determined.     

Role of entropy and autosolvation in dimerization and complexation of C60 by Zn7 metallocavitands

The supramolecular chemistry of bowl-shaped heptazinc metallocavitands templated by Schiff base macrocycles has been investigated. Dimerization thermodynamics were probed by (1)H NMR spectroscopy in benzene-d(6), toluene-d(8), and p-xylene-d(10) and revealed the process to be entropy-driven and enthalpy-opposed in each solvent. Trends in the experimentally determined enthalpy and entropy values are related to the thermodynamics of solvent autosolvation, solvent molecules being released from the monomeric metallocavitand cavity into the bulk solvent upon dimerization. The relationship established between experimentally measured dimerization thermodynamics and autosolvation data successfully predicts the absence of dimerization in CH(2)Cl(2) and CHCl(3) and was used to estimate the number of solvent molecules interacting with the monomeric metallocavitand in solution. Host-guest interactions between heptazinc metallocavitands and fullerene C(60) have also been investigated. Interestingly, metallocavitand-C(60) interactions are only observed in solvents that facilitate entropy-driven dimerization suggesting entropy and solvent autosolvation may be important in explaining concave-convex interactions.     

Observation of 1,6-anhydro-beta-maltose and 1,6-anhydro-beta-D-glucopyranose complexed with rubidium by NMR spectroscopy and electrospray ionization mass spectrometry.

A complex of 1,6-anhydro-beta-maltose with rubidium and that of 1,6-anhydro-beta-D-glucopyranose with rubidium were characterized using 87Rb NMR spectroscopy, diffusion-ordered NMR spectroscopy (DOSY) and electrospray ionization mass spectrometry (ESI-MS). Although subtle differences were observed in the 1H chemical shifts of 1,6-anhydro-beta-maltose in between the presence and absence of rubidium in deuterium oxide, measurements of the spin-lattice relaxation time (T1) of the 87Rb nucleus, the diffusion coefficients of 1,6-anhydro-beta-maltose using 1H DOSY and ESI-MS indicated the complex formation of 1,6-anhydro-beta-maltose with rubidium. The complex formation with rubidium was also identified for 1,6-anhydro-beta-D-glucopyranose using NMR and ESI-MS techniques.     

Preparation and characterization of inclusion complexes of pefloxacin mesylate with three kinds of cyclodextrins

The ability of alpha-cyclodextrin, beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin (alpha-CD, beta-CD and HP-beta-CD) to break pefloxacin mesylate (PM) aggregates by forming inclusion complexes has been studied using 1H NMR (nuclear magnetic resonance spectroscopy), 13C NMR and fluorescence spectra. The inclusion constants are determined to compare the corresponding inclusion capacity. Solid-inclusion complexes of PM with CDs are synthesized by coprecipitation method, and all the inclusion ratios are found to be 1:1. Additionally, spatial characterization of complexes has been proposed based on two-dimensional nuclear magnetic resonance technique (2D NMR) and spatial conformation is also investigated to propose two possible models between PM and CDs.     

Two Distinct Structures of Membrane‐Associated Homodimers of GTP‐ and GDP‐Bound KRAS4B Revealed by Paramagnetic Relaxation Enhancement

KRAS homo‐dimerization has been implicated in the activation of RAF kinases, however, the mechanism and structural basis remain elusive. We developed a system to study KRAS dimerization on nanodiscs using paramagnetic relaxation enhancement (PRE) NMR spectroscopy, and determined distinct structures of membrane‐anchored KRAS dimers in the active GTP‐ and inactive GDP‐loaded states. Both dimerize through an α4–α5 interface, but the relative orientation of the protomers and their contacts differ substantially. Dimerization of KRAS‐GTP, stabilized by electrostatic interactions between R135 and E168, favors an orientation on the membrane that promotes accessibility of the effector‐binding site. Remarkably, “cross”‐dimerization between GTP‐ and GDP‐bound KRAS molecules is unfavorable. These models provide a platform to elucidate the structural basis of RAF activation by RAS and to develop inhibitors that can disrupt the KRAS dimerization. The methodology is applicable to many other farnesylated small GTPases.