Cyclodextrin dimers as cleavable carriers of photodynamic sensitizers.

Several phthalocyanines carrying hydrophobic components have been synthesized and shown to bind to a group of cyclodextrin dimers with a carbon-carbon double bond in the linker. The complexes are soluble in water. On irradiation in the presence of oxygen, the singlet oxygen produced cleaves the olefinic linkers in the complexes, resulting in precipitation of the sensitizers. This process concentrates the sensitizers in the light beam, a process that has useful potential in photodynamic therapy.     

Dye molecules as nanosize sensors for low-temperature fuel cells

Dye molecules were suggested as a sensitive element for an optical sensor of parameters determining the efficiency of a fuel cell with a proton-exchange membrane, in which a water-methanol mixture is used as a fuel. The sensitivity of representatives of three different types of dyes to the concentrations of protons and methanol was examined.     

Cyclodextrin derivative-coated quartz crystal microbalances for alcohol sensing and application as methanol sensors.

Three novel cyclodextrin derivatives, mono(6-benzylimino-6-deoxy)-beta-cyclodextrin (2), mono-(6-cyclohexylamino-6-deoxy)-beta-cyclodextrin (3) and mono(6-benzylamino-6-deoxy)-beta-cyclodextrin (4), together with mono(6-phenylamino-6-deoxy)-beta-cyclodextrin (1), were synthesized and employed as sensing materials coated on quartz crystal microbalances (QCMs). Comparison of the responses to some alcohol and solvent vapours such as methanol, ethanol, propan-1-ol, propan-2-ol, butan-1-ol, acetone, chloroform and benzene indicated that these beta-cyclodextrin derivatives show considerable sensitivity and selectivity towards methanol. It shows a good linear relationship between the frequency shift and the methanol concentration in the range 3-160 mg L(-1) for 2-4 and 3-140 mg L(-1) for 1. The correlation coefficients are 0.9971, 0.9983, 0.9973 and 0.9977, respectively. The limit of detection (LOD) is 0.2 mg L(-1). When small amounts of other vapours co-exist, e.g., ethanol, propan-1-ol and acetone, the responses differ from that of pure methanol vapour, and a deduction method could eliminate this cross-sensitivity. The water cross-sensitivity was very low. These QCMs coated with cyclodextrin derivatives are employed as methanol sensors in the real atmosphere to detect on-line the concentration of methanol vapour.     

Novel quinoxalinophenanthrophenazine-based molecules as sensors for anions: synthesis and binding investigations

The design and synthesis of two novel quinoxalinophenanthrophenazine-based anion sensors are reported. Binding studies of these sensors with an array of mono- and polyatomic anions using UV-vis, fluorescence, and NMR titrations have shown 1:1 and 1:2 sensor-to-anion ratios. Binding constants were calculated for anions, which exhibited high affinity for the sensors, including acetate, benzoate, cyanide, and fluoride ions.     

Biquinolino-modified beta-cyclodextrin dimers and their metal complexes as efficient fluorescent sensors for the molecular recognition of steroids

A series of bridged beta-cyclodextrin (beta-CyD) dimers possessing functional tethers of various lengths was synthesized in moderate yield by the treatment of 2,2'-biquinoline- 4,4'-dicarboxylic dichloride with beta-CyD or mono[6-oligo(ethylenediamino)-6-deoxy]-beta-CyDs. The products were 2,2'-biquinoline-4,4'-dicarboxy-bridged bis(6-O-beta-CyD) (8), N,N'-bis(2-aminoethyl)-2,2'-biquinoline-4,4'-dicarboxamide-bridged bis(6-amino-6-deoxy-beta-CyD) (9), and N,N'-bis(5-amino-3-azapentyl)-2,2'-biquinoline-4,4'-dicarboxamide-bridged bis(6-amino-6-deoxy-beta-CyD) (10). The reaction of 8-10 with copper perchlorate give their copper(II) complexes 11-13 in satisfactory yields of over 77 %. All the bis(beta-CyD)s 8-13 act as efficient fluorescent sensors and display remarkable fluorescence enhancement upon addition of optically inert steroids. The inclusion complexation behaviors of 8-13 when treated with the representative steroids cholate (14), deoxycholate (15), and glycocholate (16) in aqueous solution at 25 degrees C were investigated by means of UV/Vis spectroscopy, conductivity and fluorescence measurements, circular dichroism spectroscopy, and 2D NMR spectroscopy. The tether length of bis(beta-CyD) 9 allows it to adopt a cooperative host-tether-guest binding mode in which the spacer and guest are co-included in the two CyD cavities. As a result of this cooperation, 9 has a stability constant (K(s)) about 2x10(2) times higher than that of monomodified beta-CyD 4 for inclusion complexation with cholate. Metallooligo(beta-CyD)s with four beta-CyD units have enhanced binding abilities compared with monomodified beta-CyDs. These metallo compounds have binding affinities for guest steroids that are up to 50-4.1x10(3) times higher than those of CyDs 2-4. The guest-induced fluorescence enhancement of bis(CyD)s opens a new channel for the design of sensor materials. The complex stability constants of these compounds are discussed from the viewpoint of induced-fit interaction and cooperative multiple binding between host and guest.     

Label-free and reagentless aptamer-based sensors for small molecules

A label free, reagentless aptasensor for adenosine is developed on an ISFET device. The separation of an aptamer/nucleic acid duplex by adenosine leads to the aptamer/adenosine complex that alters the gate potential of the ISFET. The sensitivity limit of the device is 5 x 10-5 M. Also, the immobilization of the aptamer/nucleic acid duplex on an Au-electrode and the separation of the duplex by adenosine mono-phosphate (AMP) enable the electrochemical detection of adenosine by faradaic impedance spectroscopy. The separation of the aptamer/nucleic acid duplex by adenosine and the formation of the aptamer/adenosine complex results in a decrease in the interfacial electron-transfer resistance in the presence of [Fe(CN)6]3-/4- as redox active substrate.     

Cyclodextrin dimers used to prevent side effects of photochemotherapy and general tumor chemotherapy

Recent developments of polyphasic tumor detection and tumor therapy including applications of dimeric cyclodextrin inclusion complexes of high affinity for Photodynamic Tumor Therapy (PTT) porphyrinoids are discussed in the light of future applications of similar methodology to general tumor chemotherapy. These approaches hopefully will end the martyrium of patients undergoing tumor chemotherapy today.     

Organized molecular assemblies as receptor centers of solid state chemical sensors

The paper discusses receptor properties of organized molecular assemblies constructed on the basis of the Langmuir-Blodgett films, modified porous SiO₂ films, and metal-oxide systems.Institute of Semiconductor Physics, Siberian Branch, Russian Academy of Sciences. Translated fromZhurnal Strukturnoi Khimii, Vol. 34, No. 6, pp. 86–89, November–December, 1993.Translated by O. Kharlamova     

Cyclodextrin Polymers as Delivery Systems for Targeted Anti-Cancer Chemotherapy

In the few last years, nanosystems have emerged as a potential therapeutic approach to improve the efficacy and selectivity of many drugs. Cyclodextrins (CyDs) and their nanoparticles have been widely investigated as drug delivery systems. The covalent functionalization of CyD polymer nanoparticles with targeting molecules can improve the therapeutic potential of this family of nanosystems. In this study, we investigated cross-linked γ- and β-cyclodextrin polymers as carriers for doxorubicin (ox) and oxaliplatin (Oxa). We also functionalized γ-CyD polymer bearing COOH functionalities with arginine-glycine-aspartic or arginine moieties for targeting the integrin receptors of cancer cells. We tested the Dox and Oxa anti-proliferative activity in the presence of the precursor polymer with COOH functionalities and its derivatives in A549 (lung, carcinoma) and HepG2 (liver, carcinoma) cell lines. We found that CyD polymers can significantly improve the antiproliferative activity of Dox in HepG2 cell lines only, whereas the cytotoxic activity of Oxa resulted as enhanced in both cell lines. The peptide or amino acid functionalized CyD polymers, loaded with Dox, did not show any additional effect compared to the precursor polymer. Finally, studies of Dox uptake showed that the higher antiproliferative activity of complexes correlates with the higher accumulation of Dox inside the cells. The results show that CyD polymers could be used as carriers for repositioning classical anticancer drugs such as Dox or Oxa to increase their antitumor activity.     

Long nanotube dielectric properties used as sensors of large molecules: a semicontinuum approach

A semicontinuum approach on the basis of an effective polarizability tensor per length and radius units is used to describe the dielectric response of a long single wall nanotube to the adsorption of an extended molecule. Changes in the permittivity ratio of the nanotube+molecule over the nanotube alone, which are directly connected to frequency shifts of the nanotube in a resonator configuration due to the presence of the molecule, provide a test of sensitivity of the system. The behavior of this ratio is analyzed for linear and circular geometries of the molecule, as a function of the tube characteristics (length and radius) and of the molecular size and polarizability distribution. Extension to three dimensional systems with a large set of polarizable centers is discussed in terms of self-polarization of the centers and morphology of the surface of the sensed system.     

Cyclodextrin nanosponges as effective gas carriers

Cyclodextrin based carbonate nanosponges were synthetized starting from native ??-cylodextrin and active carbonyl compounds i.e. carbonildiimidazole. In this work they were used to form inclusion complexes with three different gases i.e. 1-methylcyclopropene, oxygen and carbon dioxide. The encapsulation of gases were proved by direct reaction to known adduct (1-methylcyclopropene), by gravimetric analysis (CO₂) and by oxymeter (Oxygen). The complexetion of oxygen or carbon dioxide could be useful for many biomedical applications. In particular the oxygen-filled nanosponges could supply oxygen to the hypoxic tissues which are present in various deseases. 1-methylcyclopropene included in ??-cyclodextrin nanosponges showed superior antiethylenic performances in long lasting cut flowers in comparison with marketed products.     

Cyclic porphyrin dimers as hosts for coordinating ligands

Bicovalently linked tetraphenylporphyrins bearing dioxypentane groups at the opposite (transoid, H₄A) and adjacent (cisoid, H₄B) aryl groups have been synthesised. Protonation of the free-base porphyrins leads to fully protonated species H₈A⁴⁺/H₈A⁴⁺ accompanied by expansion of cavity size of the bisporphyrins. The electrochemical redox studies of these porphyrins and their Zinc(II) derivatives revealed that the first ring oxidation proceeds through a two-electron process while the second ring oxidation occurs at two distinct one-electron steps indicating unsymmetrical charge distribution in the oxidized intermediate. The axial ligation properties of the Zinc(Il) derivatives of H₄A/H₄B with DABCO and PMDA investigated by spectroscopic and single crystal X-ray diffraction studies showed predominant existence of 1: I complex. The Zn₂A.DABCO complex assumes an interesting eclipsed structure wherein DABCO is located inside the cavity between the two porphyrin planes with Zn-N distances at 2.08 and 2.22 ?. The Zn atoms are pulled into the cavity due to coordination towards nitrogen atoms of DABCO and deviate from the mean porphyrin plane by 0.35 ?. The electrochemical redox potentials of the axially ligated metal derivatives are found to be sensitive function of the relative coordinating ability of the ligands and the conformation of the hosts.     

Molecularly imprinted polymers as antibody and receptor mimics for assays,sensors and drug discovery

Biological receptors play an important role in affinity-based drug assays, biosensors, and at different stages during the modern drug discovery process. The molecular imprinting technology that has recently emerged has shown great potential for producing biomimetic receptors that challenge their natural counterparts. In this paper, we will overview recent progress in the use of molecularly imprinted polymers for drug assays, assembly of biomimetic sensors, and screening of combinatorial libraries. In addition, examples of using artificially-created binding sites to control synthetic reactions will be discussed. The screening-of-building blocks approach is expected to accelerate generation of valuable lead compounds, without the costly synthesis of large chemical libraries.     

A new dendrimer scaffold for preparing dimers or tetramers of biologically active molecules

Synthesis of a new scaffold derived from iminodipropionic acid for the preparation of peptide dimers and tetramers is described.     

Response functions for dimers and square-symmetric molecules in four-wave-mixing experiments with polarized light

Four-wave-mixing nonlinear-response functions are given for intermolecular and intramolecular vibrations of a perpendicular dimer and intramolecular vibrations of a square-symmetric molecule containing a doubly degenerate state. A two-dimensional particle-in-a-box model is used to approximate the electronic wave functions and obtain harmonic potentials for nuclear motion. Vibronic interactions due to symmetry-lowering distortions along Jahn-Teller active normal modes are discussed. Electronic dephasing due to nuclear motion along both symmetric and asymmetric normal modes is included in these response functions, but population transfer between states is not. As an illustration, these response functions are used to predict the pump-probe polarization anisotropy in the limit of impulsive excitation.     

Metal ion directed self-assembly of sensors for ions, molecules and biomolecules

Recent years have seen a surge of interest in the metal-ion directed construction of discrete molecular assemblies. Once the versatility of this approach for the construction of hitherto inaccessible molecular architectures was demonstrated, work towards fully functional systems rapidly developed. Since these architectures have a wide range of possible applications, this perspective review will focus on one important aspect of this research: the construction of hosts with optical or electrochemical sensing outputs. As this overview will illustrate, research in this area is now producing working examples of sensors for variety of ionic, molecular, and biomolecular guests.     

Cyclodextrin homo- and hetero-dimers as enzyme models

Three kinds of dimers (one homo-dimer of -CD and two kinds of hetero-dimers of -CCD and -CD) were synthesized as artificial hydrolases. The dimers were prepared by the condensation of 6-deoxy-6-(l-histidylamino)-cyclodextrin and 6 (carboxymethylthio)-6-deoxycyclodextrin with dicyclohexylcarbodiimide. The enzyme-like activities were studied by measuring the rates for the cleavage reaction of some kinds of nitrophenyl alkanoates. They showed large acceleration ability and substrate specificity for the acyl chain length of the substrate.As the acyl chain length of the substrate was longer, the transition state was more stabilized by the dimers. The only homo-dimer showed allosteric behavior with 1.8 Hill constant, whenp-nitrophenyl methoxyethoxyethoxyacetate was used for the substrate.     

Cyclodextrin dimer derivatives used as stationary phase for capillary gas chromatography

Summary Four cyclodetrin dimer derivatives were synthesized by linking two single cyclodextrin derivatives with difunctional spacer at the primary side of cyclodetrin. The separation properties of these cylodextrin dimer derivatives as CGC stationary phases were investigated and compared with those of the unbridged native cyclodextrin derivative. The results show that two recognition sites and one link spacer of these cyclodextrin dimer derivatives cooperate in separation and affect the separation of disubstituted benzene positional isomers.