Cyclotriveratrylene Research Articles

Cyclotriveratrylene (CTV) as a new chiral triacid scaffold capable of inducing triple helix formation of collagen peptides containing either a native sequence or Pro-Hyp-Gly repeats.

A new triacid scaffold is described based on the cone-shaped cyclotriveratrylene (CTV) molecule that facilitates the triple helical folding of peptides containing either a unique blood platelet binding collagen sequence or collagen peptides composed of Pro-Hyp-Gly repeats. The latter were synthesized by segment condensation using Fmoc-Pro-Hyp-Gly-OH. Peptides were coupled to this CTV scaffold and also coupled to the Kemp's triacid (KTA) scaffold. After assembly of peptide H-Gly-[Pro-Hyp-Gly]2-Phe-Hyp-Gly-Glu(OAll)-Arg-Gly-Val-Glu (OAll)-Gly-[Pro-Hyp-Gly]2-NH2 (13) by an orthogonal synthesis strategy to both triacid scaffolds, followed by deprotection of the allyl groups, the molecular constructs spontaneously folded into a triple helical structure. In contrast, the non-assembled peptides did not. The melting temperature (Tm) of (+/-) CTV[CH2C(O)N(H)Gly-[Pro-Hyp-Gly]2-Phe-Hyp-Gly-Glu-Arg-Gly-Val-Glu-Gly- [Pro-Hyp-Gly]2-NH2]3 (14) is 19 degrees C, whereas KTA[Gly-Gly-[Pro-Hyp-Gly]2-Phe-Hyp-Gly-Glu-Arg-Gly-Val-Glu-Gly- [Pro-Hyp-Gly]2-NH2]3 (15) has a Tm of 20 degrees C. Thus, it was shown for the first time that scaffolds were also effective in stabilizing the triple helix of native collagen sequences. The different stabilizing properties of the two CTV enantiomers could be measured after coupling of racemic CTV triacid to the collagen peptide, and subsequent chromatographic separation of the diastereomers. After assembly of the two chiral CTV scaffolds to the model peptide H-Gly-Gly-(Pro-Hyp-Gly)5-NH2 (24), the (+)-enantiomer of CTV 28b was found to serve as a better triple helix-inducing scaffold than the (-)-enantiomer 28a. In addition to an effect of the chirality of the CTV scaffold, a certain degree of flexibility between the CTV cone and the folded peptide was also shown to be of importance. Restricting the flexibility from two to one glycine residues resulted in a significant difference between the two collagen mimics 20a and 20b, whereas the difference was only slight when two glycine residues were present between the CTV scaffold and the peptide sequence in collagen mimics 30a and 30b.

The formation of a single-bonded (C70−)2dimer in a new ionic multicomponent complex of cyclotriveratrylene: (Cs+)2(C70−)2·CTV·(DMF)7(C6H6)0.75

The molecular structure and properties of a single-bonded (C70−)2 dimer in a new ionic complex with cyclotriveratrylene (CTV): (Cs+)2·(C70−)2·CTV·(DMF)7·(C6H6)0.75 are presented.

A supramolecular approach to fullerene-containing liquid crystals

A cyclotriveratrylene (CTV) derivative substituted with 18 surrounding long alkyl chains ( 1) is able to form a 2:1 host–guest complex with C 60 in the solid state. Observation of the brown product obtained from C 60 and the CTV derivative 1 directly after preparation by polarized optical microscopy revealed a fluid birefringent phase at room temperature corresponding to a nematic phase. When the sample is heated above 70 °C, the birefringence of the texture under the microscope disappears and the X-ray diffraction pattern is irreversibly transformed into a pattern characteristic of a cubic phase.

Intramolecular Coaggregation Behavior in Novel Cyclotriveratrylenes with Cholic Acid Podants

AbstractTwo molecules la and 1b consisting of one cyclotriveratrylene (CTV) and three cholic acid podants have been designed and synthesized. Fluorescent studies in water/dimethoxyethane mixtures reveal an intramolecular coaggregation between the CTV and the attached cholic acid moieties. Their fluorescent emission intensity increases and then decreases with the increase of water content, whereas under the same measuring conditions the intensity of CTV derivative 2a, which possesses no similar cholic acid moiety, increases and then reaches a maximum value. The intensity decrease in la and 1b has been attributed to the decrease of the microenvironmental polarity in media of increasing polarity because of the shielding effect of the hydrophobic face of the cholic acid moiety.

Supramolecular Complexation Behavior of Novel Cyclotriveratrylene Derivatives with Benzoate Pendants with C60

AbstractFour novel cyclotriveratrylene (CTV) derivatives with three benzoate pendants bearing different aliphatic chains have been prepared in good yields, starting from CTV. The complexation behavior of these CTV derivatives towards C60 in arene solvents has been measured by UV‐visible spectroscopy and high complexation constants are obtained. It is observed that the complexation is promoted pronouncedly by introducing methyl ester groups to the aromatic pendants, while this promoting effect is reduced when the methyl groups are replaced by longer alkyl groups.

A Liquid Crystalline Supramolecular Complex of C60 with a Cyclotriveratrylene Derivative

Cyclotriveratrylene (CTV) derivatives substituted with 9 (1) or 18 (2) long alkyl chains have been prepared. Whereas no liquid crystalline behavior has been observed for 1, the CTV derivative 2 has mesomorphic properties. Indeed, at room temperature compound 2 exhibits a nematic phase characterized by cybotactic groups with a local lamello-columnar order. Both CTV derivatives 1 and 2 are able to form supramolecular complexes with C60 in the solid state. In both cases, the 2:1 host-guest species have been obtained as brown compounds. No liquid crystalline behavior was observed for the supramolecular complex [C60 is included in (1)2]. In contrast, observation of the brown product obtained from C60 and the CTV derivative 2 directly after preparation by polarized optical microscopy revealed a fluid birefringent phase at room temperature. When the sample is heated above 70 degrees C, the birefringence of the texture under the microscope disappears and the X-ray diffraction pattern is transformed into a pattern characteristic of a cubic phase. For the first time in thermotropic liquid crystals, the space group of this cubic phase can be assigned as I4(1)32.

Clean, efficient syntheses of cyclotriveratrylene (CTV) and tris-(O-allyl)CTV in an ionic liquid

Cyclic cyclotriveratrylene (CTV) type supramolecular host compounds are traditionally synthesized under harsh dehydrating conditions and require the use of large quantities of organic solvent in the reaction workup. We now report both solvent-free and ionic liquid reaction media in efficient ‘green’ syntheses of CTVs under mild conditions. The ionic liquid tributylhexylammonium bis(trifluoromethylsulfonyl)amide (N6444 Imide) provides a safe, non-volatile reaction medium that is readily recycled. This methodology obviates the need for the use of large quantities of organic solvent and strong dehydrating acids yet provides pure crystalline product in high yields. Unlike most traditional synthetic routes to these compounds extensive recrystallisation or chromatographic steps are avoided and the molten salt reaction medium is readily recovered. Interestingly, condensation also occurs under ambient conditions on grinding of solid benzyl alcohol monomers with a suitable solid acid to afford the corresponding CTV. Ionic liquids have, as yet, been little explored as reaction media or solvents yet these offer significant advantages over volatile (and often toxic) organic solvents. Human exposure to potentially harmful vapours is obviated and recycling of the ionic liquid reaction medium significantly reduces waste generated. The procedures described here serve to extend the use of ionic liquids as reaction media.

Polybenzyl ether dendrimers for the complexation of [60]fullerenes

The formation of host-guest complexes between C60 and polybenzyl ether dendrimers with different central cores (phloroglucinol, meso-tetraphenylporphyrin, cyclotriveratrylene) has been investigated in organic solvents by means of 13C-NMR and UV-Vis spectroscopy. The interior of the dendrimers with a phloroglucinol core provides the correctly sized space for the inclusion of [60]fullerene and 13C-NMR studies suggest that the guest resides near the central core. In the dendrimers containing a meso-tetraphenylporphyrin (TPP) core, the absorbance of the porphyrin Soret band is substantially reduced in the presence of [60]fullerene, thus providing evidence for close vicinity of the fullerene guest to the central core. In solution, the cyclotriveratrylene (CTV) unit alone is a poor receptor for fullerene, but its functionalization with polybenzyl ether dendrons affords an internal cavity with a more appropriate shape and dimension, thus allowing complexation. Indeed, the Ka values (order of magnitude 101–102 L mol−1) increase significantly with the generation number of the surrounding dendritic substituents.

Self-Assembly of Grid and Helical Hydrogen-Bonded Arrays Incorporating Bowl-Shaped Receptor Sites That Bind Globular Molecules

Self-assembly of 1,2-dicarbadodecaborane(12) (o-carborane) and bowl-shaped cyclotriveratrylene (CTV) through bifurcated C–Hcarborane⋅⋅⋅O hydrogen bonds gives infinite arrays with 2D hexagonal grid or helical chain topologies. The in-built shape-specific receptor sites bind o-carborane in (o-carborane)2(CTV) or fullerene C70 in (C70)(o-carborane)(CTV)(1,2-dichlorobenzene) shown here.

Polymorphism of Crystalline Inclusion Complexes and Unsolvated Hosts. Part 8

Crystallization of cyclotriveratrylene (CTV) from solutions in acetone at 40°C gave a new 4 : 1 host-guest complex instead of the conventional 2 : 1 clathrate (β-phase) whose X-ray crystal structure was determined. Data for 2(C27H30O6) · 0.5(CO(CH3)2): monoclinic, P21/c, a = 18.942(4), b = 24.697(5), c = 10.508(2) A, β = 91.10(2)°, V = 4915(2) A3, Z = 8, D x = 1.257 g/cm3, T = 293 K, R = 0.077 (for 2694 reflections). One of the two crystallographically independent CTV molecules (molecule A) is stacked into columns characteristic of the CTV α- or β-phase complexes. Molecules B face each other enclathrating inside around the inversion center disordered acetone molecules giving rise to the molecular capsule. The acetone molecule is H-bonded simultaneously to both host molecules by C(H2)--H ··· O type bonds forming centrosymmetric dimers. Dimers are incorporated together with two A molecules into centrosymmetric units also by C(H2)--H ··· O type H-bonds. Packing of these units gives rise to the crystal structure of the clathrate.

Supramolecular Complexation of 1,2‐Dicarbadodecaborane(12)

An inclusion complex is formed between o-C2B10H12 and cyclotriveratrylene (CTV) in solution and in the solid state. The vector of approach of the carborane to the CTV cavity optimizes nonclassical hydrogen bonding between the CH groups and the aromatic ring centroids (shown schematically, right). The energy of each interaction is calculated to be 2.72 kcal mol-1.

Formation of smectic and columnar liquid crystalline phases by cyclotriveratrylene (CTV) and cyclotetraveratrylene (CTTV) derivatives incorporating calamitic structural units

Novel liquid crystalline oligomesogens, which consist of five, six or eight calamitic 4-cyanobiphenyl, 2-alkyl-5-phenyl-1,3,4-thiadiazole or 5-octyl-2-phenylpyrimidine units covalently linked by spacers of different length with a cyclotribenzylene central core (CTV derivatives, 2,3,7,8,12,13-hexa-substituted 10,15-dihydro-5H-tribenzo[a,d,g]cyclononenes) or a cyclotetrabenzylene central core (CTTV derivatives, 2,3,6,7,10,11,14,15-octa-substituted 5,10,15,20-tetrahydrotetrabenzo[a,d,g,j]cyclododecenes) have been synthesized. These compounds were investigated by polarizing microscopy, differential scanning calorimetry and some of them were also studied by X-ray diffraction. Many of the CTV derivatives show liquid crystalline properties. The cyanobiphenyl derivatives incorporating long spacer units have enantiotropic SA phases which can easily be supercooled. The thiadiazole derivatives and the pyrimidine derivatives have liquid crystalline phases only if the spacer units are rather short. Thiadiazole derivatives with an odd number of connecting atoms between the CTV core and the calamitic mesogens form SA phases, whereas those with even-numbered spacers display columnar mesophases. We propose that the columnar mesophases observed for these oligomesogens do not result from their ability to adopt a nearly disc-like shape. Instead, they represent ribbon phases which result from a steric frustration caused by the different space filling of the central cone-like core and the rod-like mesogenic groups. A chevron-like (banana-like) average shape of the molecules with even-numbered spacers is assumed to be responsible for the formation of the ribbon phases.Also a CTTV derivative with eight appended phenylthiadiazole mesogens displays a columnar mesophase. A nematic phase was found for the corresponding cyanobiphenyl derivative, whereas the pyrimidine derivative is not liquid crystalline.

Inclusion of Neutral and Anionic Guests within the Cavity of π-Metalated Cyclotriveratrylenes

Treatment of the chloride bridged species [{M(L)Cl(μ-Cl)}2] (M = Ru, L = 4-MeC6H4CHMe2, C6H6, or C6Me6; M = Ir, L = C5Me5) with silver salts AgX (X = BF4, CF3SO3, CF3CO2 etc.) followed by reflux with the bowl-shaped macrocycle cyclotriveratrylene (CTV) results in the clean formation of mono-, di-, and trimetallic CTV complexes [{M(L)}n(CTV)]X2n (n = 1, 2, 3). Further salts (X = ReO4-, I-) may be generated by anion metathesis. All three types of complex display novel host−guest properties. In the case of the monometallic hosts the disruption of the characteristic columnar packing mode of the CTV, a result of the presence of the metal center, leads to the inclusion of neutral and anionic guest species (NO2Me, Et2O, H{CF3CO2}2-, etc.) within the CTV cavity. For complexes where n = 2 or 3 the inclusion of anionic guests is invariably observed. The extent of anion binding has been established by means of X-ray crystal structure determinations upon various di- and trimetallic species containing BF4-, CF3SO3-, o...

Laying traps for elusive prey: recent advances in the non-covalent binding of anions

The structure and function of a new class of host molecules for the supramolecular complexation of anionic guest species are analysed within the context of other recent advances in the field. In particular, organometallic hosts basd upon the calixarenes, and the related macrocycle cyclotriveratrylene (CTV), are examined. X-Ray crystallographic results clearly demonstrate the inclusion of anionic guest species such as BF4–, I–, CF3SO3–, ReO4–etc. within the ostensibly electron-rich bowl-shaped cavities of both types of host as a result of cooperative effects arising from the presence of two or more metal centres arranged around a common binding pocket. Solution radiochemical studies show that hosts based upon CTV in particular are selective for large tetrahedral anions such as MO4–(M = Tc, Re). It is anticipated that the ability to discriminate between anions on a size and shape selective basis by means of manipulation of host cavity dimensions will pave the way towards new sensor devices and methods of environmental waste remediation.

Cyclotriveratrylene polarisation assisted aggregation of C60

Excess cyclotriveratrylene (CTV) and C60 in toluene results in micelle-like aggregation of the fullerenes arising from CTV polarisation of the fullerene, leading to a one-dimensional zigzag polymeric array of fullerenes in the solid state, each in the cavity of a CTV molecule.

Copper(II/I) Complexes of a Hexakis(bipyridyl)cyclotriveratrylene Ligand: A Redox-Induced Conformational Switch

A series of copper(II) and copper(I) complexes have been synthesized with ligands combining 6-methyl-2,2'-bipyridines with cyclotriveratrylene (CTV) (1) and with catechol (2). The electrochemical, (1)H NMR, and mass spectrometry characterizations of these complexes are described and discussed. The six pendant bipyridines of ligand 1 allow for the formation of two trinuclear copper(I) complexes [(1)Cu(3)](BF(4))(3) differing only in the conformation "vic" or "int" adopted by the ligand to fit the tetrahedral cuprous ions. Similarly, 1 generates two trinuclear copper(II) complexes in which the conformation of the ligand fits the square planar geometry of cupric ions. In both the cuprous and cupric complexes, a conformational equilibrium exists. Ligand 2 bearing two methylbipyridines has proven to be a useful model of the coordinating sites of ligand 1. In this case, two homologous copper(I) complexes are obtained, [(2)Cu]BF(4) and [(2)(2)Cu(2)](BF(4))(2), modeling respectively two possible coordination conformations of ligand 1. With copper(II), ligand 2 yields only one complex [(2)Cu](CF(3)SO(3))(2), which allows for the unambiguous identification of the conformations observed for ligand 1 complexes. The different coordinating modes of ligand 1 in the complexes mentioned are in exchange but exhibit different physical properties, thus representing a new bistable system based on conformational isomerism which exhibits an electrochemical potential hysteresis. An equilibrium constant and thermodynamic data were obtained for this system by variable-temperature cyclic voltammetry. The influence of coordinating vs noncoordinating solvents was also studied.

A deuterium NMR study of guest molecular dynamics of acetone in two organic inclusion compounds

Deuterium nuclear magnetic resonance (NMR) spectra and spin-lattice relaxation times (T1) are used to investigate the dynamics of the guest molecule, acetone, in tris(5-acetyl-3-thienyl)methane (TATM) and cyclotriveratrylene (CTV) inclusion compounds. 13C CPMAS powder NMR spectra were obtained for each clathrate, to verify inclusion. In acetone: TATM, the guest molecule is undergoing twofold reorientation about the CO bond, exchanging the two methyl groups. An activation energy of 20 (± 1.4) kJ/mol, for the two-site jump motion, was found, independently, from deuterium NMR spectra an T1 measurements. Acetone in CTV performs the same type of motion as acetone in TATM. Activation energies of 25.0 (± 3.2) kJ/mol and 24.1 (± 0.5) kJ/mol were determined using the same two techniques. both inclusion compounds, the rate of methyl rotation within the acetone molecule is greater than 108 Hz even at the lowest temperature measured (84 K). Analytical expressions for the spin-lattice relaxation time (T1), for a twofold jump, were derived. Calculated values of the effective quadrupolar coupling constant and T1min for the guests agree very well with the experimental data. The 84 K spectrum of acetone:TATM unexpectedly shows some asymmetry, the origin of which is discussed. Finally, these two clathrates are compared to the recently examined acetone: tri-ortho-thymotide inclusion compound. Key words: inclusion compounds, deuterium NMR, solid state NMR spectroscopy, molecular dynamics.

Hosting a Radioactive Guest: Binding of 99TcO4- by a Metalated Cyclotriveratrylene

Hosting a Radioactive Guest: Binding of 99TcO4- by a Metalated Cyclotriveratrylene

Cryptocalix[6]arenes; molecules with a large cavity

A new type of cavitand molecules with large cavities ( 4a–g) has been synthesized by the covalent three-point linking of a p-tert-butylcalix[6]arene to a cyclotriveratrylene (CTV) and their dynamic behavior has been studied by 1H NMR spectroscopy.

Crystal and molecular structure of cyclotriveratrylene

Slow evaporation of a solution made from rigorously dried toluene and cyclotriveratrylene (CTV) has led to crystals of the guest-free CTV. These belong to the monoclinic space groupP21/n witha=12.582(3),b=9.575(5),c=19.738(5) A,β=95.15(2)°;D c =1.26 g cm−3 forZ=4. Refinement based on 1708 observed reflections led toR=0.045. The nine-membered ring of the CTV has the expected crown conformation.