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A density functional theory (DFT) computational analysis, using the ωB97X-D functional, of a rapid amide cleavage in 2-carboxyphthalanilic acid (2CPA), where the amide group is flanked by two catalytic carboxyls, reveals key mechanistic information: (a) General base catalysis by a carboxylate coupled to general acid catalysis by a carboxyl is not operative. (b) Nucleophilic attack by a carboxylate on the amide carbonyl coupled to general acid catalysis at the amide oxygen can also be ruled out. (c) A mechanistic pathway that remains viable involves general acid proton delivery to the amide nitrogen by a carboxyl, while the other carboxylate engages in nucleophilic attack upon the amide carbonyl; a substantially unchanged amide carbonyl in the transition state; two concurrent bond-forming events; and a spatiotemporal-base rate acceleration. This mechanism is supported by molecular dynamic simulations which confirm a persistent key intramolecular hydrogen bonding. These theoretical conclusions, although not easily verified by experiment, are consistent with a bell-shaped pH/rate profile but are at odds with hydrolysis mechanisms in the classic literature.

This essay focuses on the debate between Warshel et al. (proponents of preorganization) and Menger and Nome (proponents of spatiotemporal effects) over the source of fast enzyme catalysis. The Warshel model proposes that the main function of enzymes is to push the solvent coordinate toward the transition state. Other physical-organic factors (e.g., desolvation, entropic effects, ground state destabilization, etc.) do not, ostensibly, contribute substantially to the rate. Indeed, physical organic chemistry in its entirety was claimed to be “irrelevant to an enzyme’s active site”. Preorganization had been applied by Warshel to his “flagship” enzyme, ketosteroid isomerase, but we discuss troubling issues with their ensuing analysis. For example, the concepts of “general acid” and “general base”, known to play a role in this enzyme’s mechanism, are ignored in the text. In contrast, the spatiotemporal theory postulates that enzyme-like rates (i.e., accelerations >108) occur when two functionalities are held rigidly at contact distances less than ca. 3 Å. Numerous diverse organic systems are shown to bear this out experimentally. Many of these are intramolecular systems where distances between functionalities are known. Among them are fast intramolecular systems where strain is actually generated during the reaction, thereby excluding steric compression as a source of the observed enzyme-like rates. Finally, the account ends with structural data from four active sites of enzymes, obtained by others, all showing contact distances between substrate analogues and enzyme. To our knowledge, contact distances less than the diameter of water are found universally among enzymes, and it is to this fact that we attribute their extremely fast rates given the assumption that enzymes, whatever their particular mechanism, obey elementary chemical principles.

This article proposes a model for chemical reactivity that involves singularities (“catastrophes”) in the timing of bond‐making and bond‐breaking events. The common stapler is a good mechanical analogy: As hand‐pressure is increased on the machine, the staple hardly changes its configuration until the staple suddenly bends. This is viewed as a singularity or catastrophe, defined classically as an abrupt change resulting from a smooth increase or decrease in external conditions (pressure in the case of a stapler, distance in the case of reactivity). Although experimental observations are provided to support the singularity effect, the model remains a heterodox notion at the present time.

This paper begins with a brief review of theories and concepts that have influenced today's view of enzyme catalysis: transition-state stabilization, entropy, orbital steering, proximity, and intramolecularity. The discussion then launches into the "spatiotemporal" model of enzyme catalysis in which fast intramolecular and enzymatic rates are ascribed to short distances that are imposed rigidly upon the reacting entities. An equation relating rate and distance is set forth, as are experimental and computational data supporting this relationship. Finally, enzyme systems themselves are analyzed in terms of the distance parameter and the so-called "split-site" model in which ground-state geometries play a crucial role. Among the many surprising conclusions is a transition-state stabilization by noncovalent forces (e.g., hydrogen-bonding) that are positioned far away from the actual transition-state chemistry. The model also confronts and dismisses the claim in classical enzymology that the ubiquitous enzyme-substrate complex is either inconsequential or inhibitory to the overall reaction rate.

“It takes a membrane to make sense out of disorder in biology. You have to be able to catch energy and hold it, storing precisely the needed amount and releasing it in measured shares”. So wrote Lewis Thomas in The Lives of Cells. Domains and rafts are shown in the present Review to play an important role in this amazing behavior of lipid membranes. Topics touched upon include the experimental detection of domains, their composition, domain induction, properties of rafts (a special form of domain), and the relationship of rafts to human diseases. Lipids, polymers, and proteins can contribute to this type of micro- and nanostructuring within membranes, thus imposing a new structural hierarchy on top of the classical bilayer membrane. The purpose of this Review is to develop an appreciation for the multiple organizational levels in self-assembling systems.

“It takes a membrane to make sense out of disorder in biology. You have to be able to catch energy and hold it, storing precisely the needed amount and releasing it in measured shares.” Die herausragende Rolle von Domänen und “Rafts” für das von Lewis Thomas in The Lives of Cells so treffend beschriebene Verhalten von Lipidmembranen ist Gegenstand dieses Aufsatzes. Erläutert wird der experimentelle Nachweis, der Aufbau und die Bildung von Domänen sowie die Eigenschaften von Rafts – einer speziellen Form von Domäne – und ihr möglicher Einfluss auf menschliche Krankheiten. Lipide, Polymere und Proteine können zu solchen Mikro- und Nanostrukturierungen innerhalb einer Membran beitragen, wodurch ein neuer Typ struktureller Ordnung in Doppelschichtmembranen entsteht. Ein Verständnis für diese unterschiedlichen Arten von Ordnungen innerhalb selbstorganisierter Systeme zu vermitteln, ist vorrangiges Ziel dieses Aufsatzes.

The micro- and nanoarchitectures of water-swollen hydrogels were routinely analyzed in three dimensions at very high resolution by two cryopreparation methods that provide stable low-temperature specimens for in-lens high magnification recordings. Gemini surfactants (gS), poly-N-isopropylacrylamides (p-NIP Am), and elastin-mimetic di- (db-E) and triblock (tb-E) copolymer proteins that form hydrogels have been routinely analyzed to the sub-10-nm level in a single day. After they were quench or high pressure frozen, samples in bulk planchets were subsequently chromium coated and observed at low temperature in an in-lens field emission SEM. Pre-equilibrated planchets (4–40°C) that hold 5–10 μl of hydrogel facilitate dynamic morphological studies above and below their transition temperatures. Rapidly frozen samples were fractured under liquid nitrogen, low-temperature metal coated, and observed in-lens to assess the dispersion characteristics of micelles and fragile colloidal assemblies within bulk frozen water. Utilizing the same planchet freezing system, the cryoetch-HRSEM technique removed bulk frozen water from the hydrogel matrix by low-temperature, high-vacuum sublimation. The remaining frozen solid-state sample faithfully represented the hydrogel matrix. Cryo- and cryoetch-HRSEM provided vast vistas of hydrogels at low and intermediate magnifications whereas high magnification recordings and anaglyphs (stereo images) provided a three-dimensional prospective and measurements on a molecular level.

No Abstract Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author. CCDC-183190 to CCDC-183202 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or deposit@ccdc.cam.ac.uk). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2002/z18793_s.pdf or from the author.

No Abstract Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2002/z18793_s.pdf or from the author.

Laser microelectrophoresis (coupled with conductance, fluorescence, and dynamic light scattering) is shown to be a highly instructive tool in comparing the dynamics of conventional and gemini surfactants embedded within vesicle bilayers. The following can be listed among the more important observations and conclusions: a) Cationic conventional surfactant, added to a “solid” (gel) lipid vesicle containing an anionic phospholipid, charge‐neutralizes only half the anionic charge. With a “liquid” (liquid crystalline) vesicle, however, the entire negative charge is neutralized. Thus, the cationic conventional surfactant can “flip‐flop” readily only in the liquid membrane. b) A cationic gemini surfactant charge‐neutralizes only the anionic lipid in the outer membrane leaflet of either solid or liquid membranes, thus indicating an inability to flip‐flop regardless of the phase‐state of the bilayer. c) Mixed population experiments show that surfactants can hop from one vesicle to another in liquid but not solid membranes. d) In liquid, but not solid, bilayers, a surface‐adsorbed cationic polymer can electrostatically “drag” anionic surfactant from the inner leaflet to the outer leaflet where the polymer resides. e) Peripheral fluorescence quenching experiments show that a cationic polymer, adhered to anionic vesicles, can be forced to dissociate in the presence of high concentrations of salt or an anionic polymer. f) Adsorbed polymer, of opposite charge to that imparted to vesicles by a gemini surfactant, is unable to dislocate surfactant even in a liquid membrane. g) In our systems, ionic polymers will not bind to neutral vesicles made solely of zwitterionic phospholipid. On the other hand, ionic polymers bind to neutral vesicles if charge neutrality is obtained by virtue of the membrane containing equimolar amounts of cationic and anionic surfactant. This is attributable to surfactant segregation within the bilayer. h) Experiments prove that polymer migration can occur among a population of neutral ternary vesicles.

Amphiphilic poly(amidoamine) (PAMAM) dendrimers were synthesized having an average of 7–46 hydrophobic chains of varying lengths (C10–C14) attached to the periphery of 64 amine groups. The synthesis was performed in three steps: (1) protection of a desired number of amines with BOC groups; (2) reaction of the remaining amine groups with long‐chain acid chlorides; and (3) deprotection from the BOC groups to produce the amphiphilic dendrimers as HCl salts. The behavior of the dendrimers in aqueous media was examined by pulse‐gradient spin‐echo (FT‐PGSE) NMR and dynamic light scattering. Self‐diffusion data on dendrimers with 22 or fewer chains, along with dynamic light scattering on concentrations of ≤16 wt%, gave no indication of dendrimer–dendrimer self‐assembly via hydrocarbon chains exposed on the dendrimer surface. It is concluded that dendrimers with 7–22 chains, each having 10–14 carbons, behave as unimolecular entities with chains coiled largely within the dendrimer periphery. Only when the number of chains becomes very large (ca ≥34) are chains forced externally where they can promote hydrophobically induced self‐assembly. Monomeric dendrimers possessing the full range of functional polarity have great potential in enzyme modeling. Copyright © 2001 John Wiley & Sons, Ltd.

Amphiphilic poly(amidoamine) (PAMAM) dendrimers were synthesized having an average of 7–46 hydrophobic chains of varying lengths (C10–C14) attached to the periphery of 64 amine groups. The synthesis was performed in three steps: (1) protection of a desired number of amines with BOC groups; (2) reaction of the remaining amine groups with long-chain acid chlorides; and (3) deprotection from the BOC groups to produce the amphiphilic dendrimers as HCl salts. The behavior of the dendrimers in aqueous media was examined by pulse-gradient spin-echo (FT-PGSE) NMR and dynamic light scattering. Self-diffusion data on dendrimers with 22 or fewer chains, along with dynamic light scattering on concentrations of ≤16 wt%, gave no indication of dendrimer–dendrimer self-assembly via hydrocarbon chains exposed on the dendrimer surface. It is concluded that dendrimers with 7–22 chains, each having 10–14 carbons, behave as unimolecular entities with chains coiled largely within the dendrimer periphery. Only when the number of chains becomes very large (ca ≥34) are chains forced externally where they can promote hydrophobically induced self-assembly. Monomeric dendrimers possessing the full range of functional polarity have great potential in enzyme modeling. Copyright © 2001 John Wiley & Sons, Ltd.

How easy it is to dismiss the humdrum surfactant! After all, its structure is unglamorous by present-day norms. And the surfactant has been entrenched in so many areas of commerce for so many decades that its chemistry might seem old and tired. The purpose of this review is to persuade the reader otherwise, all the while focusing on a remarkable new surfactant, the gemini. Geminis, the common name for “bis-surfactants”, can self-assemble at concentrations almost a hundredfold lower than for corresponding conventional surfactants. Surface activity can be improved a thousandfold. Geminis have already shown promise in skin care, antibacterial regimens, construction of high-porosity materials, analytical separations, and solubilization processes. Scores of patents dealing with geminis have appeared in the last few years. Indeed, geminis might well turn out, in the opinion of some, to be more useful to “l'homme de la rue” than crown ethers or fullerenes. This review delves into such topics as synthesis, critical micellization concentration, aggregate size and shape, gels, vesicles, and films. The information comes from scientists all over the world; one might say that gemini research is bathed in a continuous sunlight or summer. No prior knowledge of colloid chemistry is presupposed in this article.

Es fällt nicht schwer, über die langweilige Stoffklasse der Tenside hinwegzusehen, denn schließlich sticht deren Struktur nach heutigen Maßstäben nicht sonderlich ins Auge. Darüber hinaus sind Tensidmoleküle bereits seit Jahrzehnten in so vielen Wirtschaftsbereichen verankert, dass ihre Chemie veraltert und ausgeschöpft erscheinen mag. Dieser Aufsatz hat das Anliegen, den Leser vom Gegenteil zu überzeugen, indem er sich auf eine bemerkenswerte, neuartige Klasse von Tensiden, die Gemini-Tenside, konzentriert. Gemini-Tenside, so die allgemeine Bezeichnung für “Bis-Tenside“, können sich bei Konzentrationen von nahezu einem Hundertstel der Konzentration entsprechender herkömmlicher Tenside selbstorganisieren. Die Oberflächenaktivität kann um das Tausendfache verbessert werden. Gemini-Tenside haben bereits bei der Hautpflege, bei antibakteriellen Präparaten, beim Aufbau hochporöser Materialien, bei analytischen Trennungen und bei Solubilisierungsprozessen Anlass zu großen Hoffnungen gegeben. In den vergangenen Jahren ist eine große Zahl von Patenten erschienen, die sich mit Gemini-Tensiden befassen. Nach Meinung einiger könnte sich sehr wohl herausstellen, dass Gemini-Tenside für “Otto Normalverbraucher“ nützlicher sind als Kronenether oder Fullerene. Dieser Aufsatz befasst sich mit der Synthese, der kritischen Micellenbildungskonzentration sowie der Aggregationsgröße und -form von Gemini-Tensiden sowie mit Gemini-Tensid-Gelen, -Vesikeln und -Filmen. Das zusammengetragene Wissen stammt von Forschern aus der ganzen Welt; man könnte demzufolge sagen, die Gemini-Forschung ist eine Gebiet, “in dem die Sonne nicht untergeht“. In diesem Aufsatz werden keine Vorkenntnisse auf dem Gebiet der Kolloidchemie vorausgesetzt.

How easy it is to dismiss the humdrum surfactant! After all, its structure is unglamorous by present-day norms. And the surfactant has been entrenched in so many areas of commerce for so many decades that its chemistry might seem old and tired. The purpose of this review is to persuade the reader otherwise, all the while focusing on a remarkable new surfactant, the gemini. Geminis, the common name for “bis-surfactants”, can self-assemble at concentrations almost a hundredfold lower than for corresponding conventional surfactants. Surface activity can be improved a thousandfold. Geminis have already shown promise in skin care, antibacterial regimens, construction of high-porosity materials, analytical separations, and solubilization processes. Scores of patents dealing with geminis have appeared in the last few years. Indeed, geminis might well turn out, in the opinion of some, to be more useful to “l'homme de la rue” than crown ethers or fullerenes. This review delves into such topics as synthesis, critical micellization concentration, aggregate size and shape, gels, vesicles, and films. The information comes from scientists all over the world; one might say that gemini research is bathed in a continuous sunlight or summer. No prior knowledge of colloid chemistry is presupposed in this article.

A simple, two-step synthesis of (2-acetyldecyl)-trimethylammomum iodide, a base-labile surfactant, has been developed.

We measured the effects of two branched-chain analogs of distearoyl-phosphatidylcholine, containing either a methyl or an n-butyl group at the 8 position, on the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine. The former compound raised the bilayer to hexagonal phase transition temperature while the latter compound lowered it. The opposite effects of these amphiphiles on protein kinase C activity (inhibition and activation, respectively) correlated with their effects on lipid polymorphism. Because of the similarity of the structures of these two compounds, it seems likely that their opposite effects on the activity of protein kinase C is a result of their alteration of the lipid environment of the membrane rather than to binding to a specific site on the protein. We also compared the effects of hexachlorophene on lipid polymorphism and protein kinase C activity at high and at low calcium concentrations. We also found that the effect of hexachlorophene forming a complex with Ca2+ is to increase both the hexagonal phase forming propensity of the membrane as well as to increase the activity of protein kinase C, again demonstrating the correlation between lipid phase propensity and effects on protein kinase C activity.

Heptakis-6-amino-6-deoxy-β-cyclodextrin 2at pD = 6.50, 20°C catalyzes CH/CD exchange in malonic acid, pyruvic acid and acetaldehyde. Accelerations as large as 3800 were observed.

Die Zerreißprobe nicht bestanden haben kationische, cholesterinhaltige Phospholipid-Riesenvesikel, die Digitonin ausgesetzt wurden und abhängig vom jeweiligen Cholesteringehalt (0–50 Mol-%) zerplatzten (siehe Bild). Es ist also mit chemischen Mitteln möglich, eine Population ungleichartig zusammengesetzter Riesenvesikel dazu zu bringen, nur die Inhalte eines Teils ihrer Mitglieder freizusetzen.

We measured the effects of two branched-chain analogs of distearoyl-phosphatidylcholine, containing either a methyl or an n-butyl group at the 8 position, on the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine. The former compound raised the bilayer to hexagonal phase transition temperature while the latter compound lowered it. The opposite effects of these amphiphiles on protein kinase C activity (inhibition and activation, respectively) correlated with their effects on lipid polymorphism. Because of the similarity of the structures of these two compounds, it seems likely that their opposite effects on the activity of protein kinase C is a result of their alteration of the lipid environment of the membrane rather than to binding to a specific site on the protein.

A combination of electrophoresis, dynamic light scattering, conductometry, and fluorescence spectroscopy was applied to investigate vesicles (both in the “solid” and “liquid” states) that had been imparted with electric charge through the incorporation of ionic amphiphiles. These amphiphilic compounds comprised cardiolipin (with two negative charges), sodium dodecyl sulfate (with one negative charge), and cetylpyridinium bromide (with one positive charge). By this means it was discovered that negative vesicles could be converted into neutral vesicles, and then into positive vesicles, by the addition of a cationic surfactant. The amount of cationic surfactant required for the conversion depended upon the mobility of the surfactant within the bilayer. Vesicles were found to be capable of absorbing large amounts of surfactant, both cationic and anionic, before ultimately disintegrating and releasing their contents. Mixtures of cationic and anionic vesicles were able to exchange surfactant, and thereby neutralize each other's charges, without any concurrent vesicle fusion. This phenomenon is reliable only if the vesicles are in the liquid state. Finally, a biphasic exchange process was observed in which a surfactant rapidly departs from one bilayer and then enters another, while a fluorescently labeled lipid travels the reverse path only slowly.

A screening process uncovered a heterogeneous catalytic system that hydrolyzes one of two nearly identical ketals in several diketals with a high selectivity.

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Stickiness of giant vesicles, visible under the light microscope, can be promoted or prevented (see figure) by substances such as poly‐L‐lysine (cationic), polyvinylpyrrolidone (nonionic; yellow), and heparin (anionic; blue). In one particular system, adhesion was time‐dependent owing to exchange of components by a pair of electrostatically adhered vesicles.

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Zwei Riesenvesikelmit entgegengesetzter Ladung heften sich bei Berührung aneinander, was sich durch Phasenkontrast‐Mikroskopie beobachten läßt. Eine der Vesikel platzt anschließend und umhüllt die andere als entgegengesetzt geladene Schicht (siehe schematische Darstellung unten). Dieser Vorgang läßt sich wiederholen und so zur Herstellung alternierend geladener mehrschichtiger Membranen nutzen.

The rupture of cationicgiant vesicles(see the picture) in the presence of anionic vesicles, or the reverse, on exposure to digitonin is dependent on the respective cholesterol levels (0–50 mol%). Thus a disparate giant vesicle population can be chemically induced to release the contents from only a portion of its members.

Two giant vesiclesof opposite charge are seen by phase-contrast microscopy to “snap together” when brought into contact with each other. One of the vesicles then bursts, thereby surrounding the other with a layer of opposite charge (shown schematically below). The process can be repeated to construct alternating layers.

The activation energies for four Smiles reactions vary with the distance squared between the nucleophilic and electrophilic atoms consistent with theoretical considerations and pertinent to organic and enzymatic catalyses.

The activation energies for four Smiles reactions vary with the distance squared between the nucleophilic and electrophilic atoms (consistent with theoretical considerations and pertinent to organic and enzymatic catalyses).

Removal of the liquid from a glycoluril-based gel produces a macroporous solid (a xerogel) comprised of closely packed fibers that assemble into highly convoluted sheets.

A hydrolytically stable sugar phosphonate coupled to a steroid via a long and semi-rigid spacer (synthesized via a 12-step sequence) binds both to the mannose-6-phosphonate receptors of certain cancer cells and to the lipid bilayer of vesicles, thereby serving as a multivalent adhesive between cell and vesicle surfaces.

Oxford University Press, Oxford 2009. 254 S., geb. 14.99 €.—ISBN 978‐0199550029

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

For Abstract see ChemInform Abstract in Full Text.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.