Beauty and fascination of morphologies of the micro- and macrocosmos

Summary Twenty years of experience of the authors with scanning electron microscopy (SEM) led to the idea to present a collection of striking examples of micrographs of intrinsic structural beauty as a birthday present to Professor Fresenius. Harmonic structures, marvellous or scurrilous SEM micrographs of inorganic materials are followed by some examples from the living microcosmos. Sometimes, striking parallelisms to our macroscopic world can be detected, which ultimately lead to some outstanding macroscopic morphologies of the Tyrolean Alps. This is an experiment which tries to encompass fascinating morphologies of the microcosmos and morphologies of the environment of the authors, the Tyrolean Alps. It should empasize the totalitarian aspect of our existence as scientists in a specific environment although one of the authors has recently moved to a less dramatic landscape.Dedicated to Professor Dr. Wilhelm Fresenius on the occasion of his 80th birthday     

Kinetics and mechanisms of chlorine dioxide and chlorite oxidations of cysteine and glutathione

Chlorine dioxide oxidation of cysteine (CSH) is investigated under pseudo-first-order conditions (with excess CSH) in buffered aqueous solutions, p[H+] 2.7-9.5 at 25.0 degrees C. The rates of chlorine dioxide decay are first order in both ClO2 and CSH concentrations and increase rapidly as the pH increases. The proposed mechanism is an electron transfer from CS- to ClO2 (1.03 x 10(8) M(-1) s(-1)) with a subsequent rapid reaction of the CS* radical and a second ClO2 to form a cysteinyl-ClO2 adduct (CSOClO). This highly reactive adduct decays via two pathways. In acidic solutions, it hydrolyzes to give CSO(2)H (sulfinic acid) and HOCl, which in turn rapidly react to form CSO3H (cysteic acid) and Cl-. As the pH increases, the (CSOClO) adduct reacts with CS- by a second pathway to form cystine (CSSC) and chlorite ion (ClO2-). The reaction stoichiometry changes from 6 ClO2:5 CSH at low pH to 2 ClO2:10 CSH at high pH. The ClO2 oxidation of glutathione anion (GS-) is also rapid with a second-order rate constant of 1.40 x 10(8) M(-1) s(-1). The reaction of ClO2 with CSSC is 7 orders of magnitude slower than the corresponding reaction with cysteinyl anion (CS-) at pH 6.7. Chlorite ion reacts with CSH; however, at p[H+] 6.7, the observed rate of this reaction is slower than the ClO2/CSH reaction by 6 orders of magnitude. Chlorite ion oxidizes CSH while being reduced to HOCl, which in turn reacts rapidly with CSH to form Cl-. The reaction products are CSSC and CSO3H with a pH-dependent distribution similar to the ClO2/CSH system.     

Graphical analysis and visualization of three-dimensional properties of molecules and solids

A simple approach is presented for visualizing three-dimensional properties of molecular and crystalline systems by using PC-based molecular drawing software. This allows a scientist with lower-cost PC-graphics capability to carry out analysis of data, such as wave functions and electron density, which would otherwise require a dedicated graphics workstation and expensive specialized software. In this approach, a data set [x,y,z,f1(x,y,z)] is transformed to a new set of data [x,y,z] for values of f1 meeting specified requirements. The function f1, which varies throughout a chemical system is difficult to visualize. However, a more manageable data set is obtained if the set of Cartesian coordinates corresponding to locations in the system where f1 has a specified value are used. This set of points can then be visualized and plotted with standard graphics software or PC-based molecular modeling programs. In addition, the use of PC-based molecular graphics permits one to superimpose the data describing molecular properties on drawings of the molecular geometry. The entire object can then be rotated to facilitate a clear analysis of the property of the molecule.     

Facile N-arylation of amines and sulfonamides and o-arylation of phenols and arenecarboxylic acids

An efficient, transition-metal-free procedure for the N-arylation of amines, sulfonamides, and carbamates and O-arylation of phenols and carboxylic acids has been achieved by allowing these substrates to react with a variety of o-silylaryl triflates in the presence of CsF. Good to excellent yields of arylated products are obtained under very mild reaction conditions. This chemistry readily tolerates a variety of functional groups.     

Synthesis and properties of benzophenone-spiropyran and naphthalene-spiropyran conjugates

We have designed and synthesized four compounds integrating luminescent and photochromic components in their molecular skeletons. Two of them combine a nitrospiropyran photochrome with either one or two naphthalene fluorophores and can be prepared in three synthetic steps. The other two consist of a nitrospiropyran photochrome and a benzophenone phosphore connected by either ether or ester linkages and can be prepared in six or five, respectively, synthetic steps. The luminescent components of these assemblies are expected to transfer energy intramolecularly to the photochromic species upon excitation and encourage their photoisomerization. Consistently, the phosphorescence of the benzophenone units and the fluorescence of the naphthalene components are effectively quenched when these species are connected covalently to a nitrospiropyran. Nonetheless, the photoisomerization of the photochrome becomes significantly less efficient after the covalent attachment to the luminescent partner. The fraction of incident radiations absorbed by either the benzophenone or the naphthalene fragment does not promote the isomerization of the photochromic appendage. Instead, irreversible transformations occur upon irradiation of the luminophore-photochrome assemblies. Thus, the covalent attachment of a benzophenone or a naphthalene to a nitrospiropyran is not a viable strategy to improve the photocoloration efficiency of the photochromic component. Even although the very same luminophores are known to sensitize intermolecularly the isomerization of nitrospiropyrans, the transition to covalent luminophore-photochrome assemblies tends to promote degradation, rather than sensitization, upon irradiation.     

Total synthesis and biological evaluation of halipeptins A and D and analogues

The marine-derived halipeptins A (1a) and D (1d) and their analogues 3a, 3d and 4a, 4d were synthesized starting from building blocks 10, 13, 14a or 14d, 15, and 16. The first strategy for assembling the building blocks, involving a macrolactamization reaction to form the 16-membered ring hydroxy thioamide 52d as a precursor, furnished the epi-isoleucine analogue (4d) of halipeptin D, whereas a second approach involving thiazoline formation prior to macrolactamization led to a mixture of halipeptins A (1a) and D (1d) and their analogues 3a, 3d (epimers at the indicated site) and 4a, 4d (epimers at the indicated site). The same route starting with D-Ala resulted in the exclusive formation of the epimeric halipeptin D analogue 3d. The synthesized halipeptins, together with the previously constructed oxazoline analogues 5d and 6d, were subjected to biological evaluation revealing anti-inflammatory properties for 1a, 1d, and 6d while being noncytotoxic against human colon cancer cells (HCT-116).     

Synthesis of sulfur analogues of methyl and allyl kojibiosides and methyl isomaltoside and conformational analysis of the kojibiosides

The synthesis of methyl and allyl 5′-thio--D-kojibiosides and methyl 5′-thio--D-isomaltoside is described. The phenylselenoglycoside and trichloroacetimidate of 2,3,4,6-tetra-O-acetyl-5-thioglucose have been employed as glycosyl donors to glycosylate glucopyranosyl acceptors with 2-OH and 6-OH positions free. The disaccharides thus obtained are potential glucosidase inhibitors. The conformational preferences of allyl 5′-thiokojibioside (34) were studied by comparison of experimental NOE curves with the theoretical counterparts for the corresponding methyl glycoside 25, derived from a Boltzmann-averaged grid search using the program PIMM91. Very good agreement of experimental NOE curves derived from selective NOE measurments with the theoretical curves is found. The data are consistent with the population of a global minimum structure (Φ=−43, Ψ=−39 degrees) to the extent of 90%, and a second local minimum (Φ=−36, Ψ=−173 degrees) to the extent of 6%. An X-ray crystal structure of 34 at 190 K (R=4.2%) indicates a conformation (Φ=−46, Ψ=−23 degrees) that is similar to that of the global minimum.     

Synthesis and Reactions of Enediynes and Enyne-Allenes

The thermal cycloaromatization reactions of (Z)-3-hexene-1,5-diynes (enediynes) and (Z)-1,2,4-heptatrien-6-ynes (enyne-allenes) provide easy entries to a variety of carbon biradicals. Several new synthetic routes to these highly unsaturated compounds were developed by using multifunctional reagents properly substituted with combinations of boron, silicon, and tin appendages. Condensation of γ-(trialkylsilyl)allenylboranes 1 and 2 with conjugated acetylenic and allenic aldehydes followed by the elimination step of the Peterson olefination reaction furnished enediynes and enyne-allenes with high geometric purity. Convenient procedures for the synthesis of enediynes and enyne-allenes were also developed by using alkenylboronic ester 28 and the trimethyltin-substituted alkenylboranes 34 for cross-coupling reactions. On heating, acyclic enyne-allene 22 underwent a sequence of intramolecular transformations through biradical intermediates to form 26 , providing a new example of a one-step 0 → ABCD ring construction of the tetracyclic-steroidal skeleton.     

Synthesis and evaluation of sphinganine analogues of KRN7000 and OCH

[structures: see text] The phytosphingosine-containing alpha-galactosylceramides (alpha-GalCers), KRN7000 and OCH, have been shown to activate NKT cells via interaction with CD1d, a member of the CD1 family of antigen presenting proteins. Evidence from KRN7000 stimulation of NKT cells suggests that alpha-GalCers may have applications in the treatment or prevention of a range of viral, bacterial, and autoimmune conditions. Moreover, OCH, a truncated analogue of KRN7000, appears to induce a T(H)2 bias, which could have implications for the treatment of autoimmune and inflammatory conditions. We have prepared the direct sphinganine-containing analogues of KRN7000 and OCH, 1 and 2, and found them to be comparable in activity to the parent compounds in inducing the release of IL-2, IL-4, and IFNgamma. In addition, compound 2 leads to a cytokine bias similar to that seen with OCH. This is significant because sphinganines are more easily accessed than phytosphingosines, which should facilitate SAR studies.     

Re-entrant kinetic arrest and elasticity of concentrated suspensions of spherical and nonspherical repulsive and attractive colloids

We have designed and studied a new experimental colloidal system to probe how the weak shape anisotropy of uniaxial particles and variable repulsive (Coulombic) and attractive (van der Waals) forces influence slow dynamics, shear elasticity, and kinetic vitrification in dense suspensions. The introduction of shape anisotropy dramatically delays kinetic vitrification and reduces the shear elastic modulus of colloidal diatomics relative to their chemically identical spherical analogs. Tuning the interparticle interaction from repulsive, to nearly hard, to attractive by increasing suspension ionic strength reveals a nonmonotonic re-entrant dynamical phase behavior (glass-fluid-gel) and a rich variation of the shear modulus. The experimental results are quantitatively confronted with recent predictions of ideal mode coupling and activated barrier hopping theories of kinetic arrest and elasticity, and good agreement is generally found with a couple of exceptions. The systems created may have interesting materials science applications such as flowable ultrahigh volume fraction suspensions, or responsive fluids that can be reversibly switched between a flowing liquid and a solid nonequilibrium state based on in situ modification of suspension ionic strength.     

Conjugates of stimuli-responsive polymers and biomolecules: Random and site-specific conjugates of temperature-sensitive polymers and proteins

Intelligent polymers exhibit sharp, reversible phase changes in response to small changes in environmental conditions. For example, a small temperature change can cause a sharp precipitation or gelation of a smart polymer solution. Conjugation of these unusual polymers to biomolecules such as enzymes, ligands, lipids, and drugs can lead to many new and exciting applications in medicine and biotechnology. (1–4) This presentation reviews the principles, methodolgies and applications of these “smart” polymer-biomolecule systems, with special focus on temperature-sensitive polymer-protein conjugates.     

Gas-phase basicities of serine and dipeptides of serine and glycine

The gas-phase basicities of serine and dipeptides containing amino acid residues of serine and glycine were determined by proton transfer reactions in a Fourier transform ion cyclotron resonance mass spectrometer. The gas-phase basicity (GB) of L-serine was found to be 205.9 kcal/mol, with addition of a hydroxymethyl group (?CH₂OH) increasing the basicity by 4.5 kcal/mol relative to the simplest amino acid glycine (GB = 201.4 kcal/mol). This is attributed to a combination of intramolecular hydrogen bonding, induction, and symmetry effects. For the dipeptides, addition of a hydroxymethyl group does not result in a large increase in basicity relative to the basicity of glycylglycine (GB = 208.0 kcal/mol). The gas-phase basicities determined for glycyl-l-serine, l-serylglycine, and l-sery-l-serine are 209.3,210.6, and 210.9 kcal/mol, respectively. In comparison to glycylglycine, addition of the hydroxymethyl group at the N terminus has a greater impact on basicity than its placement at the C terminus. These data suggest that the protonation site for these dipeptides is the N-terminal amino nitrogen.     

Tutorial and comprehensive computational study of acceptance and transmission of sinusoidal and digital ion guides

A quadrupoles acceptance is a measure of its ability to catch ions with certain trajectories. One way to calculate acceptance is the method of ellipses. The method arose partly from a simplification that trajectories could be calculated for an electrode axis independently of others. It has been used to calculate the acceptance and transmission of sine‐driven quadrupole mass filters for over 50 years. Although the method is straightforward, it is generally described with little detail or presented as a confusing string of equations. As such, it may not be decipherable by all practitioners. For this reason, the first half of this paper presents a practical explanation of the method of ellipses and the concepts that make it work. Only equations necessary to describe the method are introduced. The tutorial also prepares the reader for the second half, which presents an alternative approach for calculating acceptance based on an array of initial trajectories. The alternative approach is used to compare the acceptance of simplified sinusoidal and digital ion guides. The method of ellipses was applied to validate results of the new approach for calculation of acceptance.     

Analysis and prediction of combinatorial chemistry synthesis and screening data

The goal of combinatorial chemistry is to simultaneously synthesize sets of compounds possessing properties that are then distinguished through screening. As the size of a compound set increases, data analysis becomes more challenging. Analysis of Variance (ANOVA) is an accepted statistical method that offers a straightforward solution to this problem. Two steps encountered by combinatorial scientists appear well suited to ANOVA: the prediction of synthetic outcomes (purity and yield) of set members and the analysis of screening data to identify combinations of reagent inputs that result in molecules with a desired property. To illustrate, a subset of a combinatorial array, referred to as a reaction rehearsal set, is evaluated to create a model predictive of the individual synthetic outcomes of the full matrix. In a second exercise, the biochemical screening data obtained from a combinatorial library is analyzed to identify reagent interactions that result in molecules possessing the sought activity.     

Melting and freezing characteristics and structural properties of supported and unsupported gold nanoclusters

Molecular dynamics simulations in conjunction with MEAM potential models have been used to study the melting and freezing behavior and structural properties of both supported and unsupported Au nanoclusters within a size range of 2 to 5 nm. In contrast to results from previous simulations regarding the melting of free Au nanoclusters, we observed a structural transformation from the initial FCC configuration to an icosahedral structure at elevated temperatures followed by a transition to a quasimolten state in the vicinity of the melting point. During the freezing of Au liquid clusters, the quasimolten state reappeared in the vicinity of the freezing point, playing the role of a transitional region between the liquid and solid phases. In essence, the melting and freezing processes involved the same structural changes which may suggest that the formation of icosahedral structures at high temperatures is intrinsic to the thermodynamics of the clusters, rather than reflecting a kinetic phenomenon. When Au nanoclusters were deposited on a silica surface, they transformed into icosahedral structures at high temperatures, slightly deformed due to stress arising from the Au-silica interface. Unlike free Au nanoclusters, an icosahedral solid-liquid coexistence state was found in the vicinity of the melting point, where the cluster consisted of coexisting solid and liquid fractions but retained an icosahedral shape at all times. These results demonstrated that the structural stability in the structures of small Au nanoclusters can be enhanced through interaction with the substrate. Supported Au nanoclusters demonstrated a structural transformation from decahedral to icosahedral motifs during Au island growth, in contrast to the predictions of the minimum-energy growth sequence: icosahedral structures appear first at very small cluster sizes, followed by decahedral structures, and finally FCC structures recovered at very large cluster sizes. The simulations also showed that island shapes are strongly influenced by the substrate, more specifically, the structural characteristic of a Au island is not only a function of size, but also depends on the contact area with the surface, which is controlled by the wetting of the cluster to the substrate.     

Resurrection and Reactivation of Acetylcholinesterase and Butyrylcholinesterase

Organophosphorus (OP) nerve agents and pesticides present significant threats to civilian and military populations. OP compounds include the nefarious G and V chemical nerve agents, but more commonly, civilians are exposed to less toxic OP pesticides, resulting in the same negative toxicological effects and thousands of deaths on an annual basis. After decades of research, no new therapeutics have been realized since the mid-1900s. Upon phosphylation of the catalytic serine residue, a process known as inhibition, there is an accumulation of acetylcholine (ACh) in the brain synapses and neuromuscular junctions, leading to a cholinergic crisis and eventually death. Oxime nucleophiles can reactivate select OP-inhibited acetylcholinesterase (AChE). Yet, the fields of reactivation of AChE and butyrylcholinesterase encounter additional challenges as broad-spectrum reactivation of either enzyme is difficult. Additional problems include the ability to cross the blood brain barrier (BBB) and to provide therapy in the central nervous system. Yet another complication arises in a competitive reaction, known as aging, whereby OP-inhibited AChE is converted to an inactive form, which until very recently, had been impossible to reverse to an active, functional form. Evaluations of uncharged oximes and other neutral nucleophiles have been made. Non-oxime reactivators, such as aromatic general bases and Mannich bases, have been developed. The issue of aging, which generates an anionic phosphylated serine residue, has been historically recalcitrant to recovery by any therapeutic approach—that is, until earlier this year. Mannich bases not only serve as reactivators of OP-inhibited AChE, but this class of compounds can also recover activity from the aged form of AChE, a process referred to as resurrection. This review covers the modern efforts to address all of these issues and notes the complexities of therapeutic development along these different lines of research.     

Confirmation and prevention of halogen exchange: practical and highly efficient one-pot synthesis of dibromo- and dichloropyridazinones

Commercially available anilines were converted by a two step, one-pot process to the corresponding pyridazinones in good to excellent yields. During the process research, a significant halogen exchange was confirmed and prevented which allowed the process to be scaled to multikilogram quantities.     

Vibrational spectroscopy and study of the state and properties of catalysts

Conclusions It can be seen from the list of publications that the method of vibrational spectroscopy has a very broad application in catalysis. A distinctive characteristic of the present situation in this field is the transition to quantitative characterization of the properties of heterogeneous catalysts and to a wider use of theoretical calculations of normal vibrations in very diverse problems, and to a classifying by these means the properties of the substances studied. In the very near future, we can expect a considerable intensification of these trends, and development of more precise methods for the investigation of the properties of surface of solid bodies based on Raman spectroscopy.Institute of Catalysis, Siberian Branch, Academy of Sciences of the USSR. Translated from Zhurnal Strukturnoi Khimii, Vol. 28, No. 3, pp. 133–144, May–June, 1987.     

Ozonolysis and combination of ozonolysis and radiolysis of aqueous fluorene

The degradation of fluorene, a toxic and carcinogenic substance formed by combustion of fossil fuels, was studied in alkaline, aqueous solution. It is very efficiently decomposed by ozonation, where 9-fluorenone and 9-fluorene carboxylic acid appear as major products in addition to a mixture of aldehydes and carboxylic acids. A more efficient substrate decomposition was observed by a treatment with γ-rays in the presence of ozone. The yield of the main products was in the case 4-times lower compared to those obtained by ozonation only. Some probable reaction steps are presented for explanation of the products.