Substantial rate enhancements of the esterification reaction of phthalic anhydride with methanol at high pressure and using supercritical CO2 as a co-solvent in a glass microreactor.

The esterification reaction of phthalic anhydride with methanol was performed at different temperatures in a continuous flow glass microreactor at pressures up to 110 bar and using supercritical CO(2) as a co-solvent. The design is such that supercritical CO(2) can be generated inside the microreactor. Substantial rate enhancements were obtained, viz. a 53-fold increase was obtained at 110 bar and 60 degrees C. Supercritical CO(2) as a co-solvent gave rise to a 5400-fold increase (both with respect to batch experiments at 1 bar at the same temperature).

Monolayer-functionalized microfluidics devices for optical sensing of acidity.

This paper describes the integration of opto-chemosensors in microfluidics networks. Our technique exploits the internal surface of the network as a platform to build a sensing system by coating the surface with a self-assembled monolayer and subsequently binding a fluorescent sensing molecule to the monolayer. Fluorescent molecules were used that can switch between a fluorescent and a non-fluorescent state, depending on the acidity of the surrounding solution. Two systems were investigated. The first employs surface confinement of a Rhodamine B dye in a glass micro channel that serves as a molecular switch in organic solutions. Upon rinsing the micro channels with acidic or basic solutions it was possible to switch between the fluorescent and non-fluorescent forms reversibly. Moreover, this system could be used to monitor the mixing of two solutions of different acidity along the micro channel. To widen the scope of optical sensing in micro channels an Oregon Green dye derivative was immobilized, which functions as a sensing molecule for pH differences in aqueous solutions. In this case, a hybrid system was used consisting of a glass slide and PDMS channels. The fluorescence intensity was found to be directly correlated to the pH of the solution in contact, indicating the possibility of using such a system as a pH sensor. These systems allow real-time measurements and can be easily implemented in micro- and nanofluidics systems thus enabling analysis of extremely small sample volumes in a fast and reproducible manner.

Single molecule photobleaching probes the exciton wave function in a multichromophoric system.

The exciton wave function of a trichromophoric system is investigated by means of single molecule spectroscopy at room temperature. Individual trimers exhibit superradiance and loss of vibronic structure in emission spectrum, features proving exciton delocalization. We identify two distinct photodegradation pathways for single trimers upon sequential photobleaching of the chromophores. The rate of each pathway is a measure for the contribution of the separate dyes to the collective excited state of the system, in this way probing the wave function of the delocalized exciton.

Fluorescence quenching of dye molecules near gold nanoparticles: radiative and nonradiative effects.

The radiative and nonradiative decay rates of lissamine dye molecules, chemically attached to differently sized gold nanoparticles, are investigated by means of time-resolved fluorescence experiments. A pronounced fluorescence quenching is observed already for the smallest nanoparticles of 1 nm radius. The quenching is caused not only by an increased nonradiative rate but, equally important, by a drastic decrease in the dye's radiative rate. Assuming resonant energy transfer to be responsible for the nonradiative decay channel, we compare our experimental findings with theoretical results derived from the Gersten-Nitzan model.

Synthesis beyond the molecule.

Weak, noncovalent interactions between molecules control many biological functions. In chemistry, noncovalent interactions are now exploited for the synthesis in solution of large supramolecular aggregates. The aim of these syntheses is not only the creation of a particular structure, but also the introduction of specific chemical functions in these supramolecules.

Nanostructures via noncovalent synthesis: 144 hydrogen bonds bring together 27 components.

This paper describes the spontaneous and reversible assembly of approximately 20 kDa synthetic hydrogen-bonded assemblies via the formation of 144 cooperative hydrogen bonds. These nanostructures ( approximately 3.0 x 5.5 nm), consisting of 27 different components, have been carefully characterized using a combination of (1)H NMR spectroscopy, MALDI-TOF MS using Ag(+)-labeling, gel permeation chromatography, and CD spectroscopy.

Synthetic self-assembled models with biomimetic functions.

Self-assembly can be considered a powerful tool in the hand of chemists for the understanding, modeling and mimicking of biological systems. The possibility of reproducing biological functions in synthetic systems obtained by self-assembly is envisioned as a modest but very important step towards the understanding of the mystery of life and its emergence on Earth.

Influencing the binding selectivity of self-assembled cyclodextrin monolayers on gold through their architecture.

Cyclodextrin derivatives modified with seven thioether moieties (1) or with one thiol moiety (2) bind to gold. Monolayers on gold of 1 or mixed monolayers of 2 and mercaptoundecanol were characterized by electrochemistry, wettability, and atomic force microscopy (AFM). Monolayers of 1 are well-ordered, but the order in the mixed monolayers depends on the ratio of 2 to mercaptoundecanol. With sufficient alkyl chains to fill the space under the cyclodextrin moiety of 2, the monolayers are densely packed. Guest recognition at these monolayers in water was studied by surface plasmon resonance (SPR) spectroscopy. For simple organic guests, monolayers of 1 showed the same selectivity and binding strength as beta-cyclodextrin in solution: however, the selectivity towards steroidal bile salts differs from solution. The mixed monolayers of 2, in which the cyclodextrin is less substituted and has more flexibility, bind steroidal guests (6a-6e) with the same selectivity as beta-cyclodextrin in solution.

Amplification of chirality: the "sergeants and soldiers" principle applied to dynamic hydrogen-bonded assemblies.

The amplification of supramolecular chirality has been studied in dynamic chiral hydrogen-bonded assemblies 1(3).(CA)(6) using "Sergeants and Soldiers" experiments. Previously, we have shown that chiral centers present in either the dimelamine component 1 or the cyanurate component CA quantitatively induce one handedness (M or P) in the assembly. This offers the possibility to study the amplification of chirality under two different kinetic regimes. When chiral dimelamines 1 are used, the exchange of chiral components and (M/P)-interconversion, i.e., interconversion between the (M)- and (P)-isomers of assembly 1(3).(CA)(6), take place via identical pathways (condition A). When chiral cyanurates CA are used, the exchange of chiral components occurs much faster than (M/P)-interconversion (condition B). Experimentally, a much stronger chiral amplification is observed under condition B. For example, the observed chiral amplification for a mixture of chiral and achiral components (40:60) is 46% under condition B and 32% under condition A. Kinetic models were developed to fit the experimental data and to simulate chiral amplification in dynamic systems in general. These simulations show that it is theoretically possible that the diastereomeric excess in a dynamic system is more than 99% with less than 1% chiral component present!

Sol-gel immobilization of serine proteases for application in organic solvents.

The serine proteases alpha-chymotrypsin, trypsin, and subtilisin Carlsberg were immobilized in a sol-gel matrix and the effects on the enzyme activity in organic media are evaluated. The percentage of immobilized enzyme is 90% in the case of alpha-chymotrypsin and the resulting specific enzyme activity in the transesterification of N-acetyl-L-phenylalanine ethyl ester with 1-propanol in cyclohexane is 43 times higher than that of a nonimmobilized lyophilized alpha-chymotrypsin. The activities of trypsin and subtilisin Carlsberg are enhanced with 437 and 31 times, respectively. The effect of immobilization on the enzyme activity is highest in hydrophobic solvents.

Complexation and (templated) synthesis of rhenium complexes with cyclodextrins and cyclodextrin dimers in water.

Several small, lipophilic rhenium complexes form inclusion complexes with native beta-cyclodextrin (beta-CD) and beta-CD dimers. Association constants larger than 10(9)M(-1) were obtained using dimers. The use of beta-CD also enabled the synthesis of these rhenium complexes in water, in excellent yields, through complexation of the otherwise insoluble corresponding ligands. The influence of the reaction time and temperature on the configuration of the reaction products has been investigated in depth for one of these complexes. Using a beta-CD dimer, it proved possible to specifically template the formation of one configuration. The strength of the complexes of the rhenium complexes in cyclodextrin dimers may allow radiolabeling of biomolecules.

Chiral exciton coupling of merocyanine dyes within a well defined hydrogen-bonded assembly.

Multichromophoric hydrogen-bonded assemblies 1(3) small middle dot(BAR)(6) are studied that bear a remarkably close resemblance to commelinin, a naturally occurring assembly responsible for an intense blue color of flowers. The incorporated chromophores exhibit a hypsochromic shift in the UV/visible (Vis) absorption maximum (Delta lambda(max) = 14 nm) compared with the free chromophores. In addition, the chiroptical properties of incorporated chromophores can be rationally controlled by changing the supramolecular chirality of the assembly. These properties have been used to study the stability of this type of assembly with UV and CD spectroscopy at concentrations far below the NMR sensitivity threshold (10(-4) M). The determined C(50%) values of 2-3 microM in benzene show the extremely high stability of these hydrogen-bonded assemblies.

Water-soluble adamantane-terminated dendrimers possessing a rhenium core.

A novel type of radiometal-containing dendrimer with potential radiotherapeutical applications is described. Different generations of this adamantane-terminated, Fréchet-type dendrimer (28, 29, 30), each consisting of two dendritic wedge ligands around a rhenium core, have been synthesized in organic solvent via reaction with ReO(PPh(3))(2)Cl(3). Through complexation of their adamantane groups by beta-cyclodextrins (beta-CDs), these dendrimers were made water soluble (9.6, 0.4, and 0.2 mM, respectively). beta-CD-induced solubilization of the wedges in water allowed the complexes to be made under aqueous conditions, via reaction with rhenium gluconate. Not only does this strategy enable the facile synthesis of the radioactive analogue, the yields for these complex-formation reactions in water also turned out to be far higher than those observed for the reactions in organic solvents.

Thermodynamic stabilities of linear and crinkled tapes and cyclic rosettes in melamine--cyanurate assemblies: a model description.

In this paper we describe model calculations for the self-assembly of N,N-disubstituted melamines 1 and N-substituted cyanuric acid or 5,5-disubstituted barbituric acid derivatives 2 into linear or crinkled tapes and cyclic rosettes via cooperative hydrogen bond formation. The model description considers all possible stereoisomeric tape structures consisting of two to eight different components (270 different species in total) and one cyclic hexameric rosette structure. Furthermore, eight steric parameters (R(12)-R(28)) are included that represent the different types of steric interactions within the assemblies. Most importantly, the model calculations clearly show that the tape/rosette ratio is very sensitive to changes in parameters that directly affect the internal energy of the rosette structure. In this respect, three parameters have been characterized, i.e., the basic equilibrium constant K(0) for the bimolecular association of a melamine and cyanurate, the equilibrium constant K(r)/K(0) for the cyclization of a linear hexamer, and the parameter R(12)-a(Z)b, representing attractive or repulsive interactions between adjacent melamine and cyanurate moieties. For example, an increase in K(0) from 100 to 10,000 M(-1) ([A](0) = [B](0) = 10 mM, K(r) = 0.01 M) or in K(r) from 0.001 to 0.1 M ([A](0) = [B](0) = 10 mM, K(0) = 1000 M(-1)) raises the concentration of the rosette from <5 to approximately 90% or from approximately 10 to approximately 85%, respectively. Similarly, a change in R(12)-a(Z)b from 1.0 (no repulsive or attractive interactions) to 1.5 (slight attractive interaction) raises the rosette fraction of the mixture from 25% to 45%. In sharp contrast to this, the model calculations show that parameters that only affect the internal energy of the tapes (R(13)--R(28)) hardly change the tape/rosette ratio. For example, by changing R(13)-a(EE)a from 1.0 (no repulsive or attractive interactions) to 0.001 (maximum repulsion), the rosette fraction in the mixture changes by no more than 8%. Including all possible sterics that occur only in tapes (i.e., R(13)--R(28)), the maximum change in rosette fraction is no more than 16%. These predictions can be rationalized by considering that any change in the stability of the tapes only affects the rosette concentration by means of shifting the equilibrium between free 1 and 2 and the rosette. Since there are 270 different tapelike structures in equilibrium, this mixture represents the best buffer solution in the world. These model calculations seem to conflict with the concept of peripheral crowding as put forward by Whitesides et al., which states that bulky substituents on the periphery of the melamine (and cyanurate) components can be used to shift the tape/rosette equilibrium completely toward the rosette structure. Computer simulations (CHARMm 24.0) show that linear tapes with bulky substituents are severely distorted from planarity, while the corresponding rosette remains planar. Therefore, tapelike structures with bulky substituents are expected to have a much higher solubility than the corresponding rosettes, which can explain the observed crystal data.

Chemistry on surface-confined molecules: an approach to anchor isolated functional units to surfaces.

The synthesis of surface-confined, nanometer-sized dendrimers and Au nanoparticles was performed starting from single Pd(II) pincer adsorbate molecules (10) embedded as isolated species into 11-mercapto-1-undecanol and decanethiol self-assembled monolayers (SAMs) on gold. The coordination of monolayer-protected Au nanoclusters (MPCs) bearing phosphine moieties at the periphery (13), or dendritic wedges (8) having a phosphine group at the focal point, to SAMs containing individual Pd(II) pincer molecules was monitored by tapping mode atomic force microscopy (TM AFM). The individual Pd(II) pincer molecules embedded in the decanethiol SAM were visualized by their coordination to phosphine MPCs 13; isolated objects with a height of 3.5 +/- 0.7 nm were observed by TM AFM. Reaction of these embedded Pd(II) pincer molecules with the dendritic wedge 8 yielded individual molecules with a height of 4.3 +/- 0.2 nm.

Convergent synthesis of noncovalent metallodendrimers containing hydrophobic dendrons at the periphery.

The noncovalent synthesis of "layer-block" metallodendrimers containing hydrophobic shells of covalent dendritic wedges at the periphery is described. Starting from first- and second-generation Fréchet wedges having phosphines at their focal point, convergent dendritic growth yields third- and fourth-generation metallodendrimers in which the coordination of nitriles, pyridines, and phosphines to SCS Pd(II) pincers is used as the assembly motif. In this convergent growth, the number of terminal hydrophobic phosphine wedges increases with generation. The solubility of the dendritic structures in apolar organic solvents such as chloroform and dichloromethane increases accordingly, in contrast to previously reported metallodendrimers. All dendritic structures were characterized by (1)H and (31)P NMR spectroscopy, elemental analysis, and MALDI-TOF mass spectrometry.

Cavitand zn(II)-porphyrin capsules with high affinities for pyridines and N-methylimidazole.

Covalent cavitand Zn(II)-porphyrins 17-20 were prepared via multistep syntheses. These host molecules show moderate to excellent binding affinities to N-methylimidazole and pyridine guests. The complexing behavior strongly depends on the spacer's length, number, and rigidity, in addition to the guest size. Cavitand capping and strapping of porphyrins strongly influence the complex formation and result in a 10-700-fold enhancement of the binding strength compared to tetraphenyl Zn(II)-porphyrin.

More than just a catalyst: a novel role for benzylamine in the sol-gel transcription of organogels.

Gelator-catalyst interactions allow the transcription of the organogel structure of methyl-4,6-O-(p-nitrobenzylidene)-alpha-D-glucopyranoside (1) into its silica analogue, even in the absence of positive charges or H-bonding sites on the gelator molecule which, until now, were considered indispensable.

Highly selective optical-sensing membranes, containing calix[4]arene chromoionophores, for Pb2+ ions.

Plasticized poly(vinyl chloride) (PVC) optode membranes containing novel calix[4]arene chromoionophores 1 or 2 and one equivalent of a lipophilic anion respond to Pb2+ ions with high selectivity over alkali, alkaline-earth, and other heavy metal ions. This selectivity stems from the combination of ligand specificity and a unique ion exchange scheme that employs both monovalent metal ions and protons as the exchanged ions. Complexation of Pb2+ ions inside the membrane is accompanied by deprotonation of the chromoionophores, which causes a bathochromic shift of the absorption maximum lambda(max). The response to Pb2+ ions is modulated by pH and alkali metal ions in a fashion that is consistent with the proposed ion-exchange mechanism. Of all of the other metal ions tested, only Cs+ and Ag+ produce a color change. However, these monovalent metal ions cause hypsochromic shifts of lambda(max) instead of the bathochromic shift caused by Pb2+, because the chromoionophores remain protonated upon complexation.

Cyclodextrin dimers as receptor molecules for steroid sensors.

The dansyl-modified dimer 9 complexes strongly with the steroidal bile salts. Relative to native beta-cyclodextrin, the binding of cholate (1a) and deoxycholate (1b) salts is especially enhanced. These steroids bind exclusively in a 1:1 fashion. For other bile salts (1c-1e) both 1:1 and 1:2 complexes were observed with stabilities similar to those of native beta-cyclodextrin. This indicates that only one cavity is used, with a small contribution from the second. The difference is attributed to the absence of a 12-hydroxy group in the second group of steroids. Comparison with a dimer that lacks the dansyl moiety (6) shows that this group especially hinders the cooperative binding of la and 1b. The smaller interference in the binding of the other steroids indicates that self-inclusion of the dansyl moiety hardly occurs. This weak self-inclusion is supported by fluorescence studies. The dansyl fluorescence of dimer 9 is less blue-shifted than that of other known dansyl-appended cyclodextrin derivatives; this is indicative of a more polar micro-environment. Addition of guests causes a change in fluorescence intensity.