Tetraethylene Glycol Chains Research Articles

On the mechanism of ion transport through lipid membranes mediated by PEGylated cyclic oligosaccharides (CyPLOS): An ESR study

The mechanism underlying the ionophoric activity of CyPLOS (cyclic phosphate-linked oligosaccharide, 2), a carbohydrate-based synthetic ion transporter decorated with four tetraethylene glycol (TEG) chains, has been investigated by an integrated electron spin resonance (ESR) approach. The mode of interaction of the ionophore with lipid bilayers has been studied by quantitatively analyzing the perturbations in the ESR spectrum of an ad hoc synthesized spin-labeled CyPLOS analog (6), and, in parallel, in the spectra of spin-labeled lipids mixed with 2. The results point to a positioning of the cyclic saccharide backbone close to the lipid headgroups, largely exposed to the aqueous medium. The TEG chains, carrying a terminal benzyl group, are deeply inserted among the lipid acyl chains, showing good mobility and flexibility. As a consequence, the order of the acyl chain packing is significantly reduced, and water penetration in the bilayer is enhanced. The resulting asymmetric perturbation of the bilayer leads to its local destabilization, thus facilitating, through a non-specific mechanism, the ion transport through the membrane.

Well-Defined Alternating Copolymers of Oligo(phenylenevinylene)s and Flexible Chains

A series of alternating copolymers containing oligomeric bis(2-ethylhexyl)-p-phenylenevinylene (BEH-PPV) chromophores and conformational-flexible n-decyl or tetraethylene glycol chains were prepared. The polymerization was carried out using Sonogashira coupling conditions between monomers composed of an iodo-terminated PPV oligomer (trimer, pentamer, or septamer) and a bis(phenylacetylene)-containing flexible chain. Polymers containing the n-decyl chain attained higher molecular weights compared to the tetraethylene glycol-containing polymers. 4-Ethynylanisole-capped oligomers (trimer, pentamer, or septamer) were prepared, and their solution photophysical properties were compared to the analogous polymeric materials. The solution optical properties of the polymers were primarily determined by chromophore length of the constituent oligomers. In contrast, the thin film fluorescence spectra of the polymers showed substantial differences between n-decyl and tetraethylene glycol containing materials, suggestin...

Luminescent gels by self-assembling platinum complexes

A platinum complex bearing a tetraethylene glycol chain has been designed and its self-assembly properties investigated. In solution, only a yellow phosphorescence of the aggregated species is observed. The complex gives luminescent gels of different colours with DCM and DMF, reaching up to 60% photoluminescence quantum yield.

Donor–Acceptor Oligorotaxanes Made to Order

Five donor-acceptor oligorotaxanes made up of dumbbells composed of tetraethylene glycol chains, interspersed with three and five 1,5-dioxynaphthalene units, and terminated by 2,6-diisopropylphenoxy stoppers, have been prepared by the threading of discrete numbers of cyclobis(paraquat-p-phenylene) rings, followed by a kinetically controlled stoppering protocol that relies on click chemistry. The well-known copper(I)-catalyzed alkyne-azide cycloaddition between azide functions placed at the ends of the polyether chains and alkyne-bearing stopper precursors was employed during the final kinetically controlled template-directed synthesis of the five oligorotaxanes, which were characterized subsequently by (1)H NMR spectroscopy at low temperature (233 K) in deuterated acetonitrile. The secondary structures, as well as the conformations, of the five oligorotaxanes were unraveled by spectroscopic comparison with the dumbbell and ring components. By focusing attention on the changes in chemical shifts of some key probe protons, obtained from a wide range of low-temperature spectra, a picture emerges of a high degree of folding within the thread protons of the dumbbells of four of the five oligorotaxanes-the fifth oligorotaxane represents a control compound in effect-brought about by a combination of C-H···O and π-π stacking interactions between the π-electron-deficient bipyridinium units in the rings and the π-electron-rich 1,5-dioxynaphthalene units and polyether chains in the dumbbells. The secondary structures of a foldamer-like nature have received further support from a solid-state superstructure of a related [3]pseudorotaxane and density functional calculations performed thereon.

A set of highly water-soluble tetraethyleneglycol-substituted Zn(ii) phthalocyanines: synthesis, photochemical and photophysical properties, interaction with plasma proteins and in vitro phototoxicity

Three Zn(II) phthalocyanines substituted by hydroxyl-terminated tetraethylene glycol chains have been synthesized. In order to evaluate the potential of these highly water-soluble phthalocyanines as type II-photosensitisers for photodynamic therapy, their structure-activity relationship was assessed by determining relevant photophysical and photochemical properties, such as their aggregation behaviour in aqueous buffers, their fluorescence properties and their efficiency with regard to the generation of singlet oxygen. In addition, evidence for a negligible interaction with plasma proteins in undiluted human plasma was obtained using a recently developed bioanalytical method and compared with the fluorescence quenching approach. These results combined with in vitro data regarding the phototoxicity of these phthalocyanines against HT-29 cancer cells provide evidence for the relevance of the non-peripherally substituted derivative for further in vivo investigations.

Efficient Syntheses and Complexation Studies of Diacetylene‐Containing Macrocyclic Polyethers

AbstractA series of novel macrocyclic polyethers, phenylene–diacetylene‐containing macrocycles was synthesized in high yields by employing copper(II)‐mediated Eglinton coupling as the key macrocyclization (80–92 %). As an analogue of the bisphenylene crown ether hosts, the binding behavior of these new macrocycles was investigated by 1H NMR spectroscopy, mass spectrometry (ESI), and X‐ray crystallography. The results obtained indicate that macrocycles with tetraethylene glycol chains (3c–e) bind a paraquat guest to form [2]pseudorotaxane‐like complexes in solution and in the solid state, whereas macrocycles with triethylene glycol chains (i.e., 3f–h) bind a paraquat guest to form [3]pseudorotaxane‐like complexes, which implies that macrocycles 3f–h may be able to complex to (mono)pyridinium cations in a [2]pseudorotaxane‐like fashion in solution.

An efficient route to VEGF-like peptide porphyrin conjugates via microwave-assisted ‘click-chemistry’

Synthetic cyclopeptides, and particularly those derived from VEGF sequence, present considerable interest for the development of nanodevices devoted to tumour imaging or targeting. In order to provide selective peptide-targeted tetrapyrrolic structures, we designed two meso-porphyrin derivatives anchored to a 17-residue-long cyclopeptide, potent antagonist of VEGF receptors, via a flexible tetraethylene glycol chain. Anchoring was achieved by two different strategies: a classical secondary amide bond formation and microwave-assisted Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (‘click-chemistry’). These compounds appear to be promising candidates for applications in PDT.

In Situ PM-IRRAS Studies of an Archaea Analogue Thiolipid Assembled on a Au(111) Electrode Surface

Polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) has been applied to determine the conformation, orientation, and hydration of a monolayer of 2,3-di-O-phytanyl-sn-glycerol-1-tetraethylene glycol-dl-alpha-lipoic acid ester (DPTL) self-assembled at a gold electrode surface. This Archaea analogue thiolipid has been recently employed to build tethered lipid bilayers. By synthesizing DPT(d16)L, a DPTL molecule with a deuterium substituted tetraethylene glycol spacer, it was possible to differentiate the C-H stretch vibrations of the phytanyl chains from the tetraethylene glycol spacer and acquire the characteristic IR spectra for the chains, spacer, and lipoic acid headgroup separately. Our results show that the structure of the monolayer displays remarkable stability in a broad range of electrode potentials and that the phytanyl chains remain in a liquid crystalline state. The tetraethylene glycol chains are coiled, and the IR spectrum for this region shows that it is in the disordered state. The most significant result of this study is the information that in contrast to expectations the spacer region is poorly hydrated. Our results have implications for the design of a tethered lipid membrane based on this thiolipid.

Highly Photocytotoxic Glucosylated Silicon(IV) Phthalocyanines. Effects of Peripheral Chloro Substitution on the Photophysical and Photodynamic Properties

Two novel glucoconjugated silicon(IV) phthalocyanines (compounds 3 and 4) have been prepared and examined for their photophysical and biological properties. With two axial 1,2:5,6-di-O-isopropylidene-alpha-d-glucofuranose substituents linked to the silicon center through the tetraethylene glycol chain, both compounds are highly soluble and remain nonaggregated in N,N-dimethylformamide. The dichloro-substituted phthalocyanine 4 exhibits a weaker fluorescence emission and higher efficiency to generate singlet oxygen compared with the nonchlorinated counterpart 3 as a result of the heavy atom effect. Both compounds are highly photocytotoxic against HT29 human colorectal carcinoma and HepG2 human hepatocarcinoma cells, particularly the nonchlorinated phthalocyanine 3, of which the IC50 values are as low as 6 nM. The lower photodynamic activity of the chlorinated derivative (IC50 = 17-21 nM) can be attributed to its higher aggregation tendency in the biological media, leading to a lower efficiency to generate reactive oxygen species inside the cells. Fluorescence microscopic studies have also revealed that compound 3 has a high and selective affinity to the lysosomes, but not the mitochondria, of HT29 cells.

Noncovalent Synthesis of Water-Soluble SCS PdII Pincer Assemblies

This article describes the noncovalent synthesis of water-soluble coordination assemblies based on SCS PdII pincer moieties. Two neutral solubilizing moieties, one based on a linear carbohydrate chain and the other on tetraethylene glycol residues, have been functionalized with pyridine and phosphane ligands. The coordination of the resulting molecules to various hydrophobic, cationic mono- and multimeric SCS PdII pincer systems has been investigated by 1H and 31P NMR spectroscopy, and by MALDI-TOF mass spectrometry. In general, the assemblies with tetraethylene glycol chains display a higher solubility in water than the ones containing linear sugar moieties. A hexapincer core decorated with six linear carbohydrates forms a hydrogel. Finally, a noncovalent water-soluble metallodendrimer having 18 peripheral tetraethylene glycol groups was constructed in a convergent manner.

Tethered Bilayer Membranes Containing Ionic Reservoirs: The Interfacial Capacitance

The use of polar linkers to tether lipid bilayer membranes to a gold substrate results in a hydrophilic layer between the membrane and the gold surface. The tethering of lipid bilayer membranes to gold substrates using tetraethylene glycol chains results in a polar layer between the membrane and the gold surface. This region may sequester ions and can act as a reservoir for ions transported across the tethered lipid membrane. In the present article, we report on the electrical properties of this ionic reservoir. In particular, the Stern model of ionic distribution is used to describe the interfacial capacitance. The model combines a surface adsorption layer (Helmholtz model) and a dynamic diffuse layer of ions (Gouy−Chapman model) to describe the interfacial capacitance. This model is used to interpret data from measurements of the interfacial capacitance obtained over a range of ionic species and concentrations. Four analogues of the sulfur−tetraethylene glycol tethers have been investigated. These studies show the effects of varying the structure of the linker group and of introducing a passivation layer adjacent to the gold. Studies were also made of the influence of spacer molecules included to vary the “in-plane” two-dimensional packing. The effect of applying a dc bias potential between an external reference electrode and the gold surface was also studied. These measurements were carried out using ac impedance spectroscopy on bilayers assembled using the method of Cornell et al.6 Most data are successfully modeled as a constant Helmholtz capacitance in series with a diffuse region capacitance that depends on ionic concentration. The dependence on ionic concentration has been modeled by the Gouy−Chapman formalism. At low ionic concentrations (<20 mM), the model becomes inadequate. Deviation from the model also occurs at higher concentrations for more tightly packed membranes, in the absence of tethered spacer molecules. According to the model at very low concentrations of electrolyte, the ionic Debye length intrudes into the hydrocarbon region of the bilayer, violating the Gouy−Chapman assumption of a uniform dielectric medium in the diffuse double layer. The Helmholtz capacitance is insensitive to potential and ionic concentration. This is consistent with Helmholtz capacitance being defined by a hard sphere distance of closest approach of the ions to the gold interface over the range of concentrations studied here. The model suggests that the application of a dc potential alters the permittivity of the diffuse region as a result of water and ions being transported into the reservoir. However, the effective relative permittivity in the reservoir region varies only from 27 to 54, suggesting the reservoir has properties more akin to a dense hydrated gel with restricted ionic mobility than to a bulk electrolyte.

A new approach to controlling catenated structures

AbstractA [2]catenane comprised of a macrocyclic polyether, analagous to bisparaphenylene 34‐crown‐10 ‐ but incorporating catechol units in its tetraethyleneglycol chains – and the cyclobis(paraquat‐p‐phenylene) tetracation, has been self‐assembled and shown to exist in solution as a non‐equimolar mixture of translational isomers.

Condensation Polymers Containing Indole Derivatives

Abstract Indole-containing bifunctional monomers (diacids, dialcohols, and dialdehydes) were synthesized by using as the basic nucleus two indoles attached by a tetraethylene glycol chain. These monomers were used for the preparation of polyesters, poly-amides, and polyazomethines.