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La función de estos videos didácticos consiste en proporcionar el apoyo necesario para la adquisición de habilidades prácticas dentro del laboratorio de cara al desarrollo profesional del alumnado. La producción de los mismos está dirigida al estudiantado que cursa asignaturas del área de química orgánica en diferentes grados universitarios. Recristalización: es el método más adecuado para purificar compuestos sólidos, siempre y cuando contengan una cantidad moderada de impurezas. La técnica se basa en dos factores: la diferente solubilidad del compuesto en un determinado disolvente a temperatura ambiente y en caliente, así como la diferencia de solubilidad de la sustancia problema y de las impurezas que la acompañan. La visualización de material didáctico en forma de videos explicativos que incluye las técnicas/operaciones básicas empleadas en un laboratorio de Química Orgánica, contribuirá a una mejor comprensión/asimilación de las mismas, resultando de gran apoyo para la correcta realización de las diferentes prácticas de laboratorio.

La función de estos videos didácticos consiste en proporcionar el apoyo necesario para la adquisición de habilidades prácticas dentro del laboratorio de cara al desarrollo profesional del alumnado. La producción de los mismos está dirigida al estudiantado que cursa asignaturas del área de química orgánica en diferentes grados universitarios. Destilación simple: se emplea fundamentalmente en dos casos, separar un sólido de un líquido, y separar dos líquidos cuyos puntos de ebullición difieren en, al menos, 70 grados Centígrados. La visualización de material didáctico en forma de videos explicativos que incluye las técnicas/operaciones básicas empleadas en un laboratorio de Química Orgánica, contribuirá a una mejor comprensión/asimilación de las mismas, resultando de gran apoyo para la correcta realización de las diferentes prácticas de laboratorio.

La función de estos videos didácticos consiste en proporcionar el apoyo necesario para la adquisición de habilidades prácticas dentro del laboratorio de cara al desarrollo profesional del alumnado. La producción de los mismos está dirigida al estudiantado que cursa asignaturas del área de química orgánica en diferentes grados universitarios. Cromatografía en Columna de Gel de Sílice: es el método más general para la separación y purificación de compuestos orgánicos, sólidos o líquidos, a escala preparativa. La visualización de material didáctico en forma de videos explicativos que incluye las técnicas/operaciones básicas empleadas en un laboratorio de Química Orgánica, contribuirá a una mejor comprensión/asimilación de las mismas, resultando de gran apoyo para la correcta realización de las diferentes prácticas de laboratorio.

La función de estos videos didácticos consiste en proporcionar el apoyo necesario para la adquisición de habilidades prácticas dentro del laboratorio de cara al desarrollo profesional del alumnado. La producción de los mismos está dirigida al estudiantado que cursa asignaturas del área de química orgánica en diferentes grados universitarios. Cromatografía en Capa Fina: permite determinar el grado de pureza de un compuesto, comparar muestras, realizar el seguimiento de una reacción, así como controlar el contenido de las fracciones obtenidas. La visualización de material didáctico en forma de videos explicativos que incluye las técnicas/operaciones básicas empleadas en un laboratorio de Química Orgánica, contribuirá a una mejor comprensión/asimilación de las mismas, resultando de gran apoyo para la correcta realización de las diferentes prácticas de laboratorio.

La función de estos videos didácticos consiste en proporcionar el apoyo necesario para la adquisición de habilidades prácticas dentro del laboratorio de cara al desarrollo profesional del alumnado. La producción de los mismos está dirigida al estudiantado que cursa asignaturas del área de química orgánica en diferentes grados universitarios. Separación por Extracción: es la técnica empleada para separar un producto de una mezcla de reacción o para aislarlo de sus fuentes naturales. Una de las separaciones por extracción más empleadas es la extracción líquido-líquido, en la que un compuesto se extrae de una fase acuosa por medio de un disolvente inmiscible con el agua. Las distintas sustancias presentes se distribuyen entre las fases acuosa y orgánica de acuerdo con sus solubilidades relativas. La visualización de material didáctico en forma de videos explicativos que incluye las técnicas/operaciones básicas empleadas en un laboratorio de Química Orgánica, contribuirá a una mejor comprensión/asimilación de las mismas, resultando de gran apoyo para la correcta realización de las diferentes prácticas de laboratorio.

La función de estos videos didácticos consiste en proporcionar el apoyo necesario para la adquisición de habilidades prácticas dentro del laboratorio de cara al desarrollo profesional del alumnado. La producción de los mismos está dirigida al estudiantado que cursa asignaturas del área de química orgánica en diferentes grados universitarios. Calentamiento a Reflujo: permite mantener la reacción a temperatura constante, por ejemplo en el punto de ebullición del disolvente, el tiempo que sea necesario y sin que se produzca una pérdida del mismo. La visualización de material didáctico en forma de videos explicativos que incluye las técnicas/operaciones básicas empleadas en un laboratorio de Química Orgánica, contribuirá a una mejor comprensión/asimilación de las mismas, resultando de gran apoyo para la correcta realización de las diferentes prácticas de laboratorio.

α-Mannosidosis (AM) results from deficient lysosomal α-mannosidase (LAMAN) activity and subsequent substrate accumulation in the lysosome, leading to severe pathology. Many of the AM-causative mutations compromise enzyme folding and could be rescued with purpose-designed pharmacological chaperones (PCs). We found that PCs combining a LAMAN glycone-binding motif based on the 5N,6O-oxomethylidenemannojirimycin (OMJ) glycomimetic core and different aglycones, in either mono- or multivalent displays, elicit binding modes involving glycone and nonglycone enzyme regions that reinforce the protein folding and stabilization potential. Multivalent derivatives exhibited potent enzyme inhibition that generally prevailed over the chaperone effect. On the contrary, monovalent OMJ derivatives with LAMAN aglycone binding area-fitting substituents proved effective as activity enhancers for several mutant LAMAN forms in AM patient fibroblasts and/or transfected MAN2B1-KO cells. This translated into a significant improvement in endosomal/lysosomal function, reverting not only the primary LAMAN substrate accumulation but also the additional downstream consequences such as cholesterol accumulation. Ministerio de Economía y Competitividad SAF2016-76083-R, CTQ2015-64425-C2-1-R Junta de Andalucía FQM2012-1467 Japan Society for the Promotion of Science 17K10051

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.-- et al., The convergent preparation of Janus molecular nanoparticles by thiourea-‘‘clicking’’ of a,a0 -trehalose halves has been implemented; the strategy allows access to macrocyclic derivatives with seggregated cationic and lipophilic domains that in the presence of DNA undergo pH-dependent self-assembly into lamellar superstructures, as established by electrochemical, structural (SAXS), microscopical (TEM) and computational techniques, that mediate transfection in vitro and in vivo., We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)., The authors thank MINECO (contract numbers CTQ2012- 30821, SAF2013-44021-R, CTQ2015-64425-C2-1-R and CTQ2015-64425-C2-2-R), the Junta de Andalucía (contract number FQM2012-1467), University Complutense of Madrid (project no. UCMA05-33-010), the Government of Navarra (Department of Innovation and Industry, contract number IIQ14334.RI1), the University of Navarra Foundation (FUN), and the European Regional Development Funds (FEDER and FSE) for financial support.

This review concentrates on both the protein receptor and guest binding abilities of carbohydrate clusters based on a cyclodextrin core. The combination of both complexation abilities is the basis of one of the pursued approaches for developing site-specific drug delivery systems. Influence on the molecular recognition properties of the number of appended saccharides, the type of carbohydrate clustering and the type of the spacer arms, among other factors, are discussed.

We report the synthesis of functionalized beta-cycloaltrins having azido groups at C-3, C-6, and both C-3 and C-6 by nucleophilic epoxy ring-opening of per-2,3-anhidro-beta-cyclomannin derivatives. The value of these compounds as templates for further functionalization is exemplified by the conversion of heptakis(3,6-diazido-3,6-dideoxy)-beta-cycloaltrin into the per-3,6-diamino, per-3,6-diacetamido, per-3,6-dichloroacetamido, and per[3,6-bis(N'-ethylureido)] derivatives in good yields.

[reaction: see text] A new method for the synthesis of beta-cyclodextrin-based cluster mannosides by application of the Sonogashira cross-coupling reaction is described. The method allows for the persubstitution of the beta-cyclodextrin at either 2- and 3-positions to give two types of heptavalent clusters, at both 2- and 6-positions to give clusters with 14 mannopyranoside units and at 2-, 3-, and 6-positions to obtain clusters with 21 mannopyranoside ligands.

In order to evaluate the abil- ity of multivalent glycosides based on a -cyclodextrin core as site-specific mo- lecular carriers, a study on both the inclusion complexation behaviour and lectin binding affinity of branched and hyperbranched -cyclodextrins is pre- sented. A series of cluster galactosides constructed on -cyclodextrin scaffolds containing seven 1-thio--lactose or - lactosylamine bound to the macrocyclic core through different spacer arms were synthesised. In addition, the first syn- thesis of three first-order dendrimers based on a -cyclodextrin core contain- ing fourteen 1-thio---galactose, 1-thio--lactose and 1-thio--melibiose residues was performed. Calorimetric titrations performed at 25C in buffered aqueous solution (pH 7.4) gave the af- finity constants and the thermodynamic parameters for the complex formation of these -cyclodextrin derivatives with guests sodium 8-anilino-1-naphthalene- sulfonate (ANS) and 2-naphthalenesul- fonate, and lectin from peanut (Arachis hypogaea) (PNA). The persubstitution of the primary face of the -cyclodextrin with saccharides led to a slight increase of the binding constant values for the inclusion complexation with ANS rela- tive to the native -cyclodextrin. How- ever, the increase of the steric conges- tion due to the presence of the saccha- ride residues on the narrow rim of the - cyclodextrin may cause a decrease of the binding ability as shown for sodium 2-naphthalenesulfonate. The spacer arms are not passive elements and influence the host binding ability ac- cording to their chemical nature. PNA forms soluble cross-linked complexes with cluster galactosides and lactosides scaffolded on -cyclodextrin but not with cluster galactopyranosylamines or melibiose. Both, perbranched and hy- perbranched -cyclodextrins, form stronger complexes with PNA than the monomeric analogues. However, the use of hyperbranched CDs does not contrib- ute to the improvement of the complex stability relative to heptakis-glycocyclo- dextrin derivatives. Finally, a titration experiment with PNA and a complex formed by a heptakis lactose -cyclo- dextrin derivative with sodium 2-naph- thalenesulfonate showed the formation of a soluble cross-linked complex with stronger affinity constant and higher stoichiometry than those observed for the complex formation of PNA with the same heptakis-lactose -cyclodextrin derivative, suggesting the formation of a three component complex.

Despite being the most abundant type of biopolymers in Nature, the biological relevance of carbohydrates has systematically been underrated for decades, associating them far less sophisticated functions (structural or energy sourcing) than those unraveled for polynucleotides and proteins. The inherently large and complex diversity of carbohydrates and glycoconjugates, together with the lack of efficient technologies to either isolate them from natural sources or produce them synthetically in useful amounts, have burdened the appreciation of their utmost importance in the most fundamental biological processes. For these reasons, carbohydrate-mediated transmission of biological information was largely unexplored. However, over the decades, it became clear that the expression of complex carbohydrates is critical in the development of living systems. Nature uses this diverse repertoire of structures as codes in fundamental biological processes such as cellular differentiation, cellular signaling, fertilization or immune response, among many others. The urgency to elucidate the glycan code in terms of structure-function relationships has fuelled chemical biology approaches uncovering new frontiers in molecular biology, for which the term glycobiology had to be coined in the early 1980s'. Novel strategies for assembling oligosaccharides, glycoproteins, glycolipids and a range of glycoconjugates have flourished ever since providing access to glycomaterials for interrogating and interfering glycan function. This account focuses on the major breakthroughs made on the strategies during the last decades to synthetically reproduce the overwhelming glycodiversity, emphasizing on the dazzling array of concepts and techniques which development was required to cope with the task. In the first place, a succinct overview of the structural and functional diversity of biologically relevant saccharides and glycoconjugates will be given. Then, a selection of the most relevant strategies that composes the complex and diversity-oriented toolbox that modern carbohydrate synthesis consists on will be dissected. Finally, a selection of the most recent applications of this synthetic toolbox to chemical biology will be captured.

12 páginas, 3 figuras, 1 tabla, 4 esquemas., Three new series of potential anthrax toxin inhibitors based on the β-cyclodextrin (βCD) scaffold were developed by exploiting face-selective CuI-catalyzed azide–alkyne 1,3-cycloadditions, amine–isothiocyanate coupling, and allyl group hydroboration–oxidation/hydroxy → amine replacement reactions. The molecular design follows the “symmetry–complementarity” concept between homogeneously functionalized polycationic βCD derivatives and protective antigen (PA), a component of anthrax toxin known to form C7-symmetric pores on the cell membrane used by lethal and edema factors to gain access to the cytosol. The synthesis and antitoxin activity of a collection of βCD derivatives differing in the number, arrangement, and face location of the cationic elements are reported herein. These results set the basis for a structure–activity relationship development program of new candidates to combat the anthrax threat., This work was supported by grant number 2R44AI052894-02 from the National Institute of Allergy and Infectious Diseases (USA), grants CTQ2007-61180/PPQ and CTQ2010-15848/BQU from the Spanish Ministry of Science and Education, the European Union (FEDER), and the Junta de Andalucía. A.D.-M. and A.M.-A. are grateful to the CSIC and the Spanish Ministry of Science and Education, respectively, for pre-doctoral fellowships.

Oligosaccharides are currently recognised as having functions that influence the entire spectrum of cell activities. However, a distinct disadvantage of naturally occurring oligosaccharides is their metabolic instability in biological systems. Therefore, much effort has been spent in the past two decades on the development of feasible routes to carbohydrate mimetics which can compete with their O-glycosidic counterparts in cell surface adhesion, inhibit carbohydrate processing enzymes, and interfere in the biosynthesis of specific cell surface carbohydrates. Such oligosaccharide mimetics are potential therapeutic agents against HIV and other infections, against cancer, diabetes and other metabolic diseases. An efficient strategy to access this type of compounds is the replacement of the glycosidic linkage by amide or pseudoamide functions such as thiourea, urea and guanidine. In this review we summarise the advances over the last decade in the synthesis of oligosaccharide mimetics that possess amide and pseudoamide linkages, as well as studies focussing on their supramolecular and recognition properties.

18 páginas, 26 figuras, 5 esquemas, Oligosaccharides are currently recognised as having functions that influence the entire spectrum of cell activities. However, a distinct disadvantage of naturally occurring oligosaccharides is their metabolic instability in biological systems. Therefore, much effort has been spent in the past two decades on the development of feasible routes to carbohydrate mimetics which can compete with their O-glycosidic counterparts in cell surface adhesion, inhibit carbohydrate processing enzymes, and interfere in the biosynthesis of specific cell surface carbohydrates. Such oligosaccharide mimetics are potential therapeutic agents against HIV and other infections, against cancer, diabetes and other metabolic diseases. An efficient strategy to access this type of compounds is the replacement of the glycosidic linkage by amide or pseudoamide functions such as thiourea, urea and guanidine. In this review we summarise the advances over the last decade in the synthesis of oligosaccharide mimetics that possess amide and pseudoamide linkages, as well as studies focussing on their supramolecular and recognition properties., We thank the Spanish Ministerio de Ciencia e Innovación (MCINN, contract numbers CTQ2007-6118/PPQ and CTQ2009-14551-C02-01) and the Junta de Andalucía for the financial support.

18 páginas, 11 figuras, 4 esquemas, A molecular-diversity-oriented approach for the preparation of well-defined polycationic amphiphilic cyclodextrins (paCDs) as gene-delivery systems is reported. The synthetic strategy takes advantage of the differential reactivity of primary versus secondary hydroxyl groups on the CD torus to regioselectively decorate each rim with cationic elements and lipophilic tails, respectively. Both the charge density and the hydrophobic–hydrophilic balance can be finely tuned in a highly symmetrical architecture that is reminiscent of both cationic lipids and cationic polymers, the two most prominent types of nonviral gene vectors. The monodisperse nature of paCDs and the modularity of the synthetic scheme are particularly well suited for structure–activity relationship studies. Gel electrophoresis revealed that paCDs self-assemble in the presence of plasmid DNA (pDNA) to provide homogeneous, stable nanoparticles (CDplexes) of 70–150 nm that fully protect pDNA from the environment. The transfection efficiency of the resulting CDplexes has been investigated in vitro on BNL-CL2 and COS-7 cell lines in the absence and presence of serum and found to be intimately dependent on architectural features. Facial amphiphilicity and the presence of a cluster of cationic and hydrogen-bonding centers for cooperative and reversible complexation of the polyanionic DNA chain is crucial to attain high transgene expression levels with very low toxicity profiles. Further enhancement of gene expression, eventually overcoming that of polyplexes from commercial polyethyleneimine (PEI) polymers (22 kDa), is achieved by building up space-oriented dendritic polycationic constructs., This work was supported by the Spanish Ministerio de Innovación y Ciencia (MICINN; contract numbers CTQ2006-15515-C02-01/BQU and CTQ2007-61180/PPQ), the Junta de Andalucía (P06-FQM-01601), the CSIC, the CNRS, and FUSINT (CNR project). A.D.M. and P.B.O. are grateful for predoctoral fellowships (CSIC and MICINN, respectively).

This review concentrates on both the protein receptor and guest binding abilities of carbohydrate clusters based on a cyclodextrin core. The combination of both complexation abilities is the basis of one of the pursued approaches for developing site-specific drug delivery systems. Influence on the molecular recognition properties of the number of appended saccharides, the type of carbohydrate clustering and the type of the spacer arms, among other factors, are discussed.

A series of 2-(3,4-dichlorophenyl)-cyclopent-1-enyl carboxylic acid esters and amides were prepared and tested for binding to the DAT, SERT, and NET. The achiral compounds were easily attained and found to inhibit DAT binding with K(i)-values ranging from 0.095 to 0.00003 mM. Among the compounds tested 2-(3,4-dichlorophenyl)-cyclopent-1-enyl carboxylic acid 2-methylphenyl ester was found to be highly selective with SERT/DAT>7000; NET/DAT>1700, K(i)=60 nM.

4 páginas, 2 figuras, 3 esquemas, An efficient general strategy for the incorporation of functional elements onto the secondary hydroxyl rim of beta-cyclodextrin has been developed and applied to the synthesis of a novel series of C7-symmetric homogeneous macromolecular polycations with improved DNA complexing and delivery properties., This work was supported by the Spanish MEC (contract numbers CTQ2006-15515-C02-01/BQU and CTQ2007-61180/PPQ), the Junta de Andaluca (P06-FQM-01601), the CSIC, and the CNRS.

In our ongoing program aimed at the design, synthesis, and biological evaluation of novel gem-difluoromethylenated glycosidase inhibitors, gem-4,4-difluoromethylenated iminosugars (5-9) were synthesized. The biological evaluation of these synthetic iminosugars showed that the gem-difluoromethylenyl group generally reduced the inhibition of glycosidases. However, this was not the case at pH 5.0, where the gem-difluoromethylenated iminosugar 6 was a stronger inhibitor than comparable iminosugars 1 and 36, suggesting that the influence of this group is mainly through its effect on the amine. It is proposed that the unprotonated iminosugar is the species preferably bound by beta-glucosidase, due to the lower pK(a) value of iminosugar 6 than of 1 or 36, leaving iminosugars 1 and 36 mostly protonated at pH 5.0, while iminosugar 6 is not. Iminosugar 6 also displayed good and selective inhibition of beta-glucosidase at pH 6.8.

[reaction: see text] (6AR,6DR)-6A,6D-Di-C-cyano-beta-cyclodextrin (1) and 6A,6D-di-C-cyano-alpha-cyclodextrin (2) were synthesized and shown to catalyze hydrolysis of aryl glycosides into glucose and phenol with a reaction following Michaelis-Menten kinetics. At pH 8.0 and 59 degrees C hydrolysis of 4-nitrophenyl alpha-glucopyranoside was catalyzed by 1 with KM = 10.5 +/- 1.5 mM, kcat = 1.42(+/-0.09) x 10(-4) s(-1), and kcat/kuncat = 7922. Catalysis was observed with a concentration of 1 as low as 10 microM. Hydrolysis of the other aryl glycosides containing stereochemical variation in the sugar-moiety and 4-nitro-, 2-nitro-, 2-aldehydo-, and 2,4-dinitro- were also catalyzed by 1 and 2 with kcat/kuncat ranging from 4 to 7100. Hydrolysis of a phenyl beta-d-glucoside or the thioglycoside tolylthio beta-D-glucoside was also catalyzed. From a series of prepared analogues of 1 it was found that the catalysis was associated with the hydroxyl groups alpha to the nitril groups. The monocyanohydrin 6-C-cyano-beta-cyclodextrin (3) was also found to catalyze the hydrolysis of 4-nitrophenyl beta-glucopyranoside with kcat/kuncat = 1356. It was proposed that the cyclodextrin cyanohydrins 1-3 catalyze the hydrolysis by general acid catalysis on the bound substrate.

(6AR,6DR)-6A,6D-di-C-cyano-beta-cyclodextrin (3) was synthesized and shown to catalyze hydrolysis of nitrophenyl glycosides with the reaction following Michaelis-Menten kinetics. At pH 7.4 and 25 degrees C, hydrolysis of 4-nitrophenyl-beta-glucopyranoside (2) was catalyzed with KM = 15 mM, kcat = 8.2 x 10-6 s-1, and kcat/kuncat = 1217. Catalysis was observed with concentration of 3 as low as 10 muM. Hydrolysis of the corresponding alpha-glucoside, alpha-galactoside, alpha-mannoside, and 2-nitrophenyl-beta-galactoside was also catalyzed by 3, with kcat/kuncat ranging from 283 to 2147. A series of analogues of 3 was prepared and investigated for catalysis of the hydrolysis of 2: (6AR,6DR)-6A,6D-di-C-propyl-beta-cyclodextrin (9) was not catalytic, while 6A,6D-di-C-cyano-6A,6D-dideoxy-beta-cyclodextrin (12) had a low catalytic activity (kcat/kuncat = 4). A kcat/kuncat = 48 was found for 6A,6D-dialdehydo-beta-cyclodextrin dihydrate (11). It was proposed that 3 acts by general acid catalysis on the bound substrate.

alpha- and beta-Cyclodextrin 6(A),6(D)-diacids (1 and 2), beta-cyclodextrin-6-monoacid (14), beta-cyclodextrin 6(A),6(D)-di-O-sulfate (16) and beta-cyclodextrin-6-heptasulfate (19) were synthesised. Acids 1, 2 and 14 were made from perbenzylated alpha- or beta-cyclodextrin, by diisobutylaluminum hydride (DIBAL)-promoted debenzylation, oxidation and deprotection. Addition of molecular sieves was found to improve the debenzylation reaction. Sulfates 16 and 19 were made by sulfation of the appropriately partially protected derivatives and deprotection. Catalysis of 4-nitrophenyl glycoside cleavage by these cyclodextrin derivatives was studied. Compounds 1, 2 and 16 were found to catalyse the reaction, with the catalysis following Michaelis-Menten kinetics and depending first order on the phosphate concentration. In a phosphate buffer (0.5 M, 59 degrees C, pH 8.0), K(M) varied from 2-10 mM and the k(cat)/k(uncat) ratio from 80-1000 depending on the stereochemistry of the substrate and the catalyst, with 2 being the best catalyst and with the sulfated 16 also displaying catalytic ability. The monoacid 14 and the heptasulfate 19 were not catalytic.

In order to evaluate the ability of multivalent glycosides based on a beta-cyclodextrin core as site-specific molecular carriers, a study on both the inclusion complexation behaviour and lectin binding affinity of branched and hyperbranched beta-cyclodextrins is presented. A series of cluster galactosides constructed on beta-cyclodextrin scaffolds containing seven 1-thio-beta-lactose or beta-lactosylamine bound to the macrocyclic core through different spacer arms were synthesised. In addition, the first synthesis of three first-order dendrimers based on a beta-cyclodextrin core containing fourteen 1-thio-beta-D-galactose, 1-thio-beta-lactose and 1-thio-beta-melibiose residues was performed. Calorimetric titrations performed at 25 degrees C in buffered aqueous solution (pH 7.4) gave the affinity constants and the thermodynamic parameters for the complex formation of these beta-cyclodextrin derivatives with guests sodium 8-anilino-1-naphthalenesulfonate (ANS) and 2-naphthalenesulfonate, and lectin from peanut (Arachis hypogaea) (PNA). The persubstitution of the primary face of the beta-cyclodextrin with saccharides led to a slight increase of the binding constant values for the inclusion complexation with ANS relative to the native beta-cyclodextrin. However, the increase of the steric congestion due to the presence of the saccharide residues on the narrow rim of the beta-cyclodextrin may cause a decrease of the binding ability as shown for sodium 2-naphthalenesulfonate. The spacer arms are not passive elements and influence the host binding ability according to their chemical nature. PNA forms soluble cross-linked complexes with cluster galactosides and lactosides scaffolded on beta-cyclodextrin but not with cluster galactopyranosylamines or melibiose. Both, perbranched and hyperbranched beta-cyclodextrins, form stronger complexes with PNA than the monomeric analogues. However, the use of hyperbranched CDs does not contribute to the improvement of the complex stability relative to heptakis-glycocyclodextrin derivatives. Finally, a titration experiment with PNA and a complex formed by a heptakis lactose beta-cyclodextrin derivative with sodium 2-naphthalenesulfonate showed the formation of a soluble cross-linked complex with stronger affinity constant and higher stoichiometry than those observed for the complex formation of PNA with the same heptakis-lactose beta-cyclodextrin derivative, suggesting the formation of a three component complex.

A series of 2-(3,4-dichlorophenyl)-cyclopent-1-enyl carboxylic acid esters and amides were prepared and tested for binding to the DAT, SERT, and NET. The achiral compounds were easily attained and found to inhibit DAT binding with K(i)-values ranging from 0.095 to 0.00003 mM. Among the compounds tested 2-(3,4-dichlorophenyl)-cyclopent-1-enyl carboxylic acid 2-methylphenyl ester was found to be highly selective with SERT/DAT>7000; NET/DAT>1700, K(i)=60 nM.