Cyclic tetraureas with variable flexibility--synthesis, crystal structures and properties

Macrocyclic molecules containing several amide or urea functions may serve as anion receptors. We describe the synthesis of 32-membered macrocycles, in which four rigid xanthene units (X) and/or diphenyl ether units (D) as flexible analogues are linked via urea groups. All six possible combinations of these units (XXXX, XXXD, XXDD, XDXD, XDDD and DDDD) were synthesized and two examples were characterised by single-crystal X-ray analyses (DDDD and two structures for XXXD). Both macrocycles showed distinct differences in their overall conformation and consequently in their hydrogen-bonding pattern. Hydrogen-bonded solvent molecules are found for both compounds and intramolecular hydrogen bonds for the two structures of XXXD, but surprisingly no direct intermolecular hydrogen bonds between the macrocyclic tetraurea molecules. The interaction with various anions was studied by (1)H NMR spectroscopy. Stability constants for all tetramers were determined by UV spectroscopy for complexes with chloride, bromide, acetate and dihydrogenphosphate in acetonitrile-THF (3:1). The strongest binding was found for XXXD and acetate (log beta = 7.4 +/- 0.2), the weakest for XXXX and acetate (log beta = 5.1 +/- 0.5). MD simulations in chloroform and acetonitrile boxes show that all molecules except DDDD adopt very similar conformations characterized by an up-down-up-down arrangement of the spacer groups. Clustered solvation shells of acetonitrile molecules around XXXX and DDDD suggest their preorganization for spherical/planar and tetrahedral/bidentate anions, respectively, which in turn was corroborated by simulation of the corresponding complexes with chloride and dihydrogenphosphate.     

Preparation and unique circular dichroism phenomena of urea-functionalized self-folding resorcinarenes bearing chiral termini through asymmetric hydrogen-bonding belts

Chiral macrocycles with eight (R)- and (S)-methylbenzylurea residues on the resorcinarene skeleton linked through a hexyl or dodecyl spacer having amide linkages have been prepared by the reactions of the corresponding octaamine derivative with (R)- and (S)-alpha-methylbenzylisocyanate, respectively. In chloroform, the urea-functionalized resorcinarenes with hexyl spacers form intramolecular hydrogen bonds by bundling the urea and amide residues in a cyclic fashion to give a self-folding cavitand. The urea and amide residues are cooperatively oriented in the same direction to result in asymmetric hydrogen-bonding belts. Unique circular dichroism (CD) bands are induced in the absorption wavelength ranges of the macrocyclic skeleton, caused by a chirality transmission from their chiral urea termini through hexyl spacers in the self-folded conformation. On the other hand, urea-functionalized resorcinarenes with a longer dodecyl spacer do not show such unique CD bands on the macrocycle, because of their weaker propensity for hydrogen bond formation. The characteristic CD bands of the urea-functionalized self-folding macrocycles disappeared upon complexation with anions such as chloride and bromide, reflecting breaking of the intramolecular hydrogen-bonding belts.     

Synthesis and structure of lower rim C-linked N-tosyl peptidocalix[4]arenes

Chiral p-tert-butylcalix[4]arenes functionalized at the lower rim with amino acid residues have been prepared. The (1)H and (13)C NMR spectra indicate that the macrocycles preferably adopt a cone conformation. Calix[4]arenes bearing amino acid moieties were prepared as a class of receptors selective for anions that are bound through hydrogen bonding with the NH group. The association constants are dependent on the nature of the substituents at the lower rim. Derivative 9 shows the strongest complexation and the largest selectivity for N-tosyl-(L)-alaninate. Finally, a preliminary X-ray crystal study of the difunctionalized receptor 6f shows the "flattened cone" conformation in the solid state.     

Double-helical cyclic peptides: design, synthesis, and crystal structure of figure-eight mirror-image conformers of adamantane-constrained cystine-containing cyclic peptide cyclo (Adm-Cyst)(3)

A large number of macrocycles containing alternating repeats of cystine diOMe(-NH-CH(CO(2)Me)-CH(2)-S-)(2) and either a conformationally rigid aromatic/alicyclic moiety or a flexible polymethylene unit (X) in the cyclic backbone with ring size varying from 13- to 78-membered have been examined by spectral ((1)H NMR, FT-IR, CD) and X-ray crystallography studies for unusual conformational preferences. While (1)H NMR measurements indicated a turnlike conformation for all macrocycles, stabilized by intramolecular NH.CO hydrogen bonding, as also supported by FT-IR spectra in chloroform, convincing proof for beta-turn structures was provided by circular dichroism studies. Single-crystal X-ray studies on 39-membered cyclo (Adm-L-Cyst)(3) revealed a double-helical fold (figure-eight motif) for the macrocycle. Only a right-handed double helix was seen in the macrocycle constructed from L-cystine. The mirror-image macrocycle made up of D-cystine units exhibited a double helix with exactly the opposite screw sense, as expected. The enantiomeric figure-eights were stabilized by two intramolecular NH. CO hydrogen bonds and exhibited identical (1) H NMR and FT-IR spectra. The CD spectra of both isomers had a mirror-image relationship. The present results have clearly brought out the importance of cystine residues in inducing turn conformation that may be an important deciding factor for the adoption of topologically important structures by macrocycles containing multiple S-S linkages.     

Novel Strategies for the Complexation of Neutral Guest Molecules by Synthetic Macrocyclic Hosts

Abstract

Complexes of macrocyclic polyethers with neutral guests have been studied in solution. The first part, a systematic study of complexes of malononitrile with a variety of macrocyclic polyethers, allowed the evaluation of the thermo-dynamic parameters of complexation. The second part deals with the complexation of urea. Complexes with simple 18-membered macrocycles were prepared. Protonation of urea allowed the phase transfer of urea from aqueous to chloroform solution. Finally the complexation of urea by 2-carboxy-1,3-xylyl crown ethers is described.     

Bipyrrole- and dipyrromethane-based amido-imine hybrid macrocycles. New receptors for oxoanions

Three new amido-imine-type hybrid macrocycles based on substituted pyrrole units have been synthesized and shown to act as effective receptors for oxoanions in the solid state and in acetonitrile solution. One of the macrocycles in question, compound 15, was characterized by X-ray diffraction analysis as the free macrocycle and as a complex with sulfuric acid. A comparison of the resulting structures reveals that this receptor is capable of undergoing a conformational change and, as a consequence, varying the number of donor sites that can interact with a bound substrate. This system and the other two new receptors described in this work (macrocycles 14 and 16, respectively) display a high affinity toward oxoanions (studied as their tetrabutylammonium (TBA) salts), with association constants on the order of 10(7) M-1 being determined in acetonitrile solution using standard UV-vis spectroscopic titration methods. A competitive titration method was used to determine affinity constants in excess of ca. 10(6) M-1. Two of the receptors (14 and 15) were found to bind acetate, hydrogen sulfate, and dihydrogen phosphate anion well, and the bipyrrole-based receptor (14) was also found to bind the perrhenate anion. In contrast, the bis-dipyrromethane-derived receptor (16) was found to bind chloride anion preferentially. The unusual selectivity displayed by 16 for this spherical anion was rationalized on the basis of single-crystal X-ray diffraction data and DFT modeling calculations, which revealed a rigid structure appropriately suited for chloride anion recognition.     

Calix[6]pyrrole and hybrid calix[n]furan[m]pyrroles (n+m=6): syntheses and host-guest chemistry

Calix[6]pyrrole 2 and the "hybrid systems" calix[3]furan[3]pyrrole 12, calix[2]furan[4]pyrrole 13, and calix[1]furan[5]pyrrole 14, have been synthesized by increasing conversion of the furan units present in the readily accessible calix[6]furan 3 to pyrroles. The host-guest chemistry of these novel macrocycles towards a number of anions, including halogen ions, dihydrogen phosphate, hydrogen sulfate, nitrate, and cyanide has been investigated in solution by (1)H NMR titration techniques and/or phase transfer experiments. The solid-state structures of the free receptors 2, 12, and 13, the 1:1 complexes of calix[6]pyrrole 2 with chloride and bromide, and the 1:1 complex of 14 with chloride are also reported.     

A conformationally flexible, urea-based tripodal anion receptor: solid-state, solution, and theoretical studies

Tripodal tris(urea) cationic receptors 1 and 2 containing p-tolyl or octyl substituents, respectively, have been synthesized, and their association behavior with anionic guests has been studied via a variety of methods. The receptors are based around a hexasubstituted aryl core and contain both urea and pyridinium functionalities. For 1:1 complexes, anions reside within the central cavity of the host species, held by hydrogen bonds from both NH and CH donors. The following host-anion complexes have been characterized by X-ray crystallography: 1-(Br)3, 1-(PF6)3.2(CH3)2CO, and 1-(NO3)1.5(PF6)1.5. Each structure contains the receptor in a significantly different geometry, highlighting the anion-dependent conformational flexibility of 1. Solution 1H NMR spectroscopic titrations have shown the two host species to display significant affinity for both halides and hydrogen sulfate and strongly suggest the persistence of CH...X- interactions despite the presence of "stronger" NH donor groups. Variable-temperature 1H NMR studies on the more soluble octyl derivative 2 show that there is a distinct change in conformation associated with the formation of a 1:1 host/guest complex. Computations using density functional theory (with the B3LYP functional) have been employed to aid in understanding the geometry of the 1:1 host/chloride complexes of 1 and 2. These experiments suggest that the lowest energy conformation for 1-Cl is one in which the ureidopyridinium arms are orientated upward forming a cavity that is sealed by CH...pi interactions, effectively forming a unimolecular capsule, whereas for 2 a less symmetrical "2-up, 1-down" geometry is favored.     

Mass spectrometric study of oligourea macrocycles and their anion binding behavior

Two series, one of tris‐urea macrocycles and another of hexakis‐urea macrocycles, are examined by (tandem) Fourier‐transform ion cyclotron resonance (FTICR) mass spectrometry with respect to their fragmentation patterns and anion binding properties. All macrocycles are based on two different building blocks, one of which is a very rigid xanthene unit and the other one is a more flexible diphenyl ether. The composition and the sequence of these units thus determine their flexibility. During the fragmentation of deprotonated oligourea macrocycles in the gas phase, one urea N? CO bond is cleaved followed by a scrambling reaction within the macrocycle structure. Consequently, fragments are observed that deviate from those that would be expected from the sequence of the subunits. Interesting anion binding properties involve the simultaneous recognition of two chloride anions by one of the hexakis‐urea macrocycles, whose flexibility allows this host to form a double‐helical structure. Flexibility also determines which of the hexameric receptors bears a high sulfate affinity. The interaction energy between some of the macrocycles and sulfate is high enough to even stabilize the intrinsically unstable sulfate dianion. Copyright © 2009 John Wiley & Sons, Ltd.     

Bis-amidocarbazolyl urea receptor for short-chain dicarboxylate anions

Urea receptor 1 based on two (1-amino-8-amido-3,6-dichloro)carbazole units shows a strong association with dicarboxylate anions such as oxalate, malonate and succinate guests through multiple hydrogen bonds from the carbazole, urea and amide NH groups. (1)H NMR complexation studies exhibit high values of association constants in DMSO-d(6). X-ray structures of the 1?:?1 complexes of 1 with oxalate and malonate as their ditetrabutylammonium salts were obtained. A modelling study of the complex of receptor 1 with succinate (as its diTBA salt) showed a more reduced geometric complementarity than its homologue malonate.     

Kinetics of Complexation in the Monolayers of Amphiphilic Dicetylcyclene on the Surface of Aqueous Copper(II) Chloride Solutions

The kinetics of complexation in monolayers of dicetycyclene at the surface of aqueous copper(II) chloride solutions was studied. It was shown that the changes in the phase state of monolayer related to the conformational transitions of macrocycle are responsible for the differences in the rate and binding mechanism of copper ions. It was concluded that the sterically more advantageous (for the coordination with the metal ion) conformation of macrocyclic polyamine is ensured in a monolayer. In addition, it was established that the rate and mechanism of complexation in such monolayers greatly depend on the degree of protonation of ligands, the latter being dependent on the subphase pH. It was also demonstrated that an increase in subphase pH to 7 and higher results in an almost total suppression of metal ion binding due to strong conformational distortion of dicetylcyclene macrocycles in a monolayer and the hydrogen bonding between macrocycles.     

A naked-eye detection of fluoride with urea/thiourea receptors which have both a benzophenone group and a nitrophenyl group as a signalling group

Two new colorimetric anion sensors have been synthesised where both a benzophenone group and a nitrophenyl group were used as signalling units and urea/thiourea moieties as binding sites. The receptors, effectively and selectively, recognised fluoride and carboxylate anions from other anions such as chloride, bromide, iodide, perchlorate, hydrogen sulphate and nitrate in DMSO.     

Heterodinuclear ruthenium(II) bipyridyl-transition metal dithiocarbamate macrocycles for anion recognition and sensing

New heterodinuclear ruthenium(II) bipyridyl-transition metal dithiocarbamate macrocycles have been prepared in good yields via metal directed self-assembly and shown to recognise anions. ¹H NMR anion titration studies reveal the nature of the bipyridyl amide metal dithiocarbamate spacer unit in the respective dinuclear metal macrocycle influences significantly the strength of chloride and bromide complexation in DMSO solutions. Luminescence spectroscopy was used to sense anions in polar organic solutions via notable emission enhancement and quenching of the respective ruthenium(II) bipyridyl groups in the receptors.     

Modular functional integration of a two-input INH logic gate with a fluorophore-spacer-receptor1-spacer-receptor2 conjugate

The synthesis and photophysical characterization of a fluorophore-spacer-receptor 1-spacer-receptor 2 system, which combines the 1,8-naphthalimide fluorophore with amine and urea receptor units, is reported. Photoinduced electron transfer (PET) from the amino group was blocked by protonation, leading to a drastic fluorescence enhancement (ca. 20 times). Interaction of the urea receptor with anions (F (-), AcO (-), H 2PO 4 (-)) via hydrogen bonding or urea NH deprotonation resulted in significant fluorescence quenching of the 1,8-naphthalimide chromophore in an appropriately chosen model compound (ca. 30-45%). In the presence of both chemical input species, protons and anions, the fluorescence was also quenched. The binding of the anions by NH (+) ammonium receptor has been assumed. The apparent anion binding constants of the protonated conjugate follow the basicity trend of the anions: AcO (-) approximately F (-) > H 2PO 4 (-). The investigated system constitutes an example for the flexible and modular realization of functionally integrated INH logic at the molecular level, using protons and anions as chemical input species and the fluorescence of a PET-active signaling unit as output.     

Theoretical studies of the solvent effect on the conformation of the HO-C-C-X (X = F, NH2, NO2) moiety with competing intra- and intermolecular hydrogen bonds

Theoretical calculations up to the ab initio IEF-PCM/CCSD(T)/CBS//IEF-PCM/B3LYP/6-311++G** and IEF-PCM/B97D/aug-cc-pvtz levels have been performed for 2X-ethanol and 2X-phenol systems with X = F, NH(2), NO(2) in chloroform and aqueous solution. The calculated relative free energies by means of the IEF-PCM continuum dielectric method do not differ very much at the DFT and ab initio levels. Application of explicit solvent models and the FEP/MC method for determining relative solvation free energies causes, however, large deviations in the predicted equilibrium compositions, although the predominant conformation for the solute is generally in agreement with that from the corresponding IEF-PCM calculations. Existence of an intramolecular hydrogen bond (HB structure) for species with the HO-C-C-X moiety is preferred compared with a conformation when the hydrogen bond is disrupted (NoHB) for the considered F- and NO(2)-substituted molecules both in chloroform and aqueous solution. For 2NH(2)-ethanol, the HB structure is predominant in chloroform, whereas the 93:7 ratio for the OCCN trans/gauche species was obtained in aqueous solution. 2NH(2)-phenol exhibits a subtle equilibrium of the HB and NoHB conformations in both solvents. Potential of mean force calculations predict about a 10% solute association for the trans 2NH(2)-ethanol solute even in the fairly dilute 0.22 molar solution, whereas direct MC simulations do not support the maintenance of a doubly hydrogen-bonded dimer. Aqueous solution characteristics, as coordination numbers and numbers of strongly bound water molecules to the solute at T = 298 K and p = 1 atm, correspond reasonably to the derived molecular structures.     

Structure and dynamics of some macrocyclic pyrimidine derivatives

The conformation of macrocycles consisting of the uracil and two thiopyrimidine moieties linked by polymethylene spacers depends on the spacer length, intramolecular hydrogen bonds, and the solvent nature. In CDCl₃ the intramolecular hydrogen bond (NH) appreciably stabilizes the “skew” conformation but only for the macrocycles with methylene spacers consisting of five carbon atoms. Protonation leads to the cleavage of intramolecular hydrogen bonds, destabilization of the “skew” conformation, and self-association due to the strong intermolecular hydrogen bond involving the acid counterion, and the intermolecular bond is cleaved in a polar solvent.     

PA6/CaCl_2复合物的络合机理研究

通过负离子淤浆聚合制备了高相对黏度的聚酰胺6(PA6)粉末料,将其加入氯化钙甲酸溶液中制备不同的PA6/CaCl2单位链节摩尔比络合溶液.采用X射线光电子能谱(XPS)、红外分析方法研究了PA6/CaCl2复合物的络合机理.结果表明,复合物中钙原子与聚酰胺6分子链上的羰基氧原子发生配位作用,破坏了PA6本身的氢键,释放出自由NH,而氯离子则与NH形成氢键.同时通过电导率测试推测氯化钙与酰胺键之间的配合形式为四配位或者六配位.     

Anion-induced switching of the helical orientation of a chiral indolocarbazole dimer

An indolocarbazole dimer, containing chiral urea appendages, that adopts a helically folded conformation by intramolecular hydrogen bonds as proven by ¹H NMR and circular dichroism (CD) spectroscopy has been prepared. Owing to the preferential formation of one helical conformer, strong CD signals appear in relatively non-polar solvents such as chloroform (CHCl₃) and dichloromethane (CH₂Cl₂) but the signal is negligible in dimethyl sulfoxide (DMSO). In addition, the optical rotation of the dimer is highly sensitive to the polarity of solvents. For example, the magnitude of the specific rotation ([α]_D) is ? 934° in CH₂Cl₂ and ? 657° in CHCl₃ but it is only ? 75° in DMSO. These observations suggest that the dimer folds to a helical structure by intramolecular hydrogen bonds in relatively non-polar solvents but exists in an unfolded extended conformation in polar solvents such as DMSO. The dimer strongly binds anions such as chloride, acetate and sulfate by multiple hydrogen bonds. In addition, anion binding leads to considerable CD spectral changes with the different pattern and degree of Cotton effects depending on the kind of anions. The dimer may be therefore utilised for the construction of an anion-responsive chiroptical sensor or switch.     

Fluorescence ratiometry of monomer/excimer emissions in a space-through PET system

[Reaction: see text]. Fluorogenic calix[4]arenes (1 and 2) bearing a pendent ethyleneamine on their triazacrown rings, respectively, were synthesized in the cone conformation. Compared with 4, free 1 and 2 display a relatively weak emission, reflecting that a PET process from the pendent amine group (-CH2CH2NH2) to the fluorogenic pyrenes is mainly operated. Addition of various metal ions or anions to the solution of 1 or 2 reduces the PET because the pendent alkylamine takes part in the complexation, causing their fluorescence spectra to be changed. When Pb2+, a quenching metal ion, is added to 1 or 2, their pyrene monomer emission is enhanced with their excimer emission quenched, which is due to conformational changes of the facing carbonyl groups as well as to the participation of the ethyleneamine into the three-dimensional Pb2+ ion encapsulation. In contrast, upon addition of alkali metal ions to the 1 and 2, both monomer and excimer emissions are observed to increase, which is attributable to the CHEF effect and the retained conformations. For anion sensing, both 1 and 2 show a high selectivity for F- ions over other anions tested. When the F- ion is bound to 1 or 2 by hydrogen bonding between the amide NH of the triazacrown ring and F-, both their monomer and excimer emissions are weakened due to PET from the bound F- to the pyrene units.     

Complexation of two macrocycles for amide,saccharide, and halide derivatives: the capacity of 1,2,3-triazole as hydrogen and halogen bonding acceptors

Two 1,2,3-triazole- and amide-incorporated macrocycles have been prepared by 1,3-dipolar cycloaddition of the corresponding dialkyne and diazide precursors. Intramolecular C–H?O hydrogen bonding is introduced to lock the C⁵–H atoms of the 1,2,3-triazole rings. The binding of the two macrocycles to amide, monosaccharide, and halide derivatives in chloroform or dichloromethane has been investigated. It is revealed that the amide units dominate their binding toward the amide and monosaccharide guests through forming intermolecular hydrogen bonding and 1,2,3-triazole is as weak as an intermolecular hydrogen bonding acceptor, but it forms intermolecular halogen bonding when cooperative effect exists.