Product screening of fast reactions in IR-laser-heated liquid water filaments in a vacuum by mass spectrometry

In the present article a novel approach for rapid product screening of fast reactions in IR-laser-heated liquid microbeams in a vacuum is highlighted. From absorbed energies, a shock wave analysis, high-speed laser stroboscopy, and thermodynamic data of high-temperature water the enthalpy, temperature, density, pressure, and the reaction time window for the hot water filament could be characterized. The experimental conditions (30 kbar, 1750 K, density approximately 1 g/cm3) present during the lifetime of the filament (20-30 ns) were extreme and provided a unique environment for high-temperature water chemistry. For the probe of the reaction products liquid beam desorption mass spectrometry was employed. A decisive feature of the technique is that ionic species, as well as neutral products and intermediates may be detected (neutrals as protonated aggregates) via time-of-flight mass spectrometry without any additional ionization laser. After the explosive disintegration of the superheated beam, high-temperature water reactions are efficiently quenched via expansion and evaporative cooling. For first exploratory experiments for chemistry in ultrahigh-temperature, -pressure and -density water, we have chosen resorcinol as a benchmark system, simple enough and well studied in high-temperature water environments much below 1000 K. Contrary to oxidation reactions usually present under less extreme and dense supercritical conditions, we have observed hydration and little H-atom abstraction during the narrow time window of the experiment. Small amounts of radicals but no ionic intermediates other than simple proton adducts were detected. The experimental findings are discussed in terms of the energetic and dense environment and the small time window for reaction, and they provide firm evidence for additional thermal reaction channels in extreme molecular environments.     

Glycine on a wet pyrite surface at extreme conditions

We present ab initio molecular dynamics (MD) simulations of the simplest amino acid, glycine, at the water/pyrite interface under extreme pressure/temperature conditions. These simulations are aimed to contribute to the discussion of the "iron-sulfur world" (ISW) scenario, an intriguing proposal in the controversial field of "Origin of Life" research. The simulations show that glycine easily desorbs from a water/pyrite interface through hydrogen-bond assistance. The retention time is only of the order of a picosecond, and the surface bonding is best understood as a relatively weak electrostatic interaction. However, we have found indications of glycine activation due to the interaction with the surface, and thus for a possible reaction with a suitable anchor molecule.     

A step toward the wet surface chemistry of glycine and alanine on Cu{110}: destabilization and decomposition in the presence of near-ambient water vapor

The coadsorption of water with organic molecules under near-ambient pressure and temperature conditions opens up new reaction pathways on model catalyst surfaces that are not accessible in conventional ultrahigh-vacuum surface-science experiments. The surface chemistry of glycine and alanine at the water-exposed Cu{110} interface was studied in situ using ambient-pressure photoemission and X-ray absorption spectroscopy techniques. At water pressures above 10(-5) Torr a significant pressure-dependent decrease in the temperature for dissociative desorption was observed for both amino acids, accompanied by the appearance of a new CN intermediate, which is not observed for lower pressures. The most likely reaction mechanisms involve dehydrogenation induced by O and/or OH surface species resulting from the dissociative adsorption of water. The linear relationship between the inverse decomposition temperature and the logarithm of water pressure enables determination of the activation energy for the surface reaction, between 213 and 232 kJ/mol, and a prediction of the decomposition temperature at the solid-liquid interface by extrapolating toward the equilibrium vapor pressure. Such experiments near the equilibrium vapor pressure provide important information about elementary surface processes at the solid-liquid interface, which can be retrieved neither under ultrahigh vacuum conditions nor from interfaces immersed in a solution.     

Mechanism of bleomycin suicide: a Car-Parrinello molecular dynamics investigation

Using first-principles molecular dynamics simulations (Car-Parrinello method) we investigated the possible reaction pathways for decay of the active bleomycin-Fe(III)-OOH complex, so-called bleomycin suicide. The theoretical model of activated bleomycin contains the whole metal bonding domain of the bleomycin ligand. Simulations performed both in a vacuum and in water show that a facile decaying process involves a homolytic O-O bond cleavage with an almost simultaneous hydrogen atom abstraction. The formation of an intra- or intermolecular hydrogen bond appears to be crucial for the decay of the activated bleomycin. We did not observe any evidence of heterolytic cleavage of the O-O bond of the Fe(III)-OOH species.     

An infrared study of solid glycine in environments of astrophysical relevance

The conversion from neutral to zwitterionic glycine is studied using infrared spectroscopy from the point of view of the interactions of this molecule with polar (water) and non-polar (CO(2), CH(4)) surroundings. Such environments could be found on astronomical or astrophysical matter. The samples are prepared by vapour-deposition on a cold substrate (25 K), and then heated up to sublimation temperatures of the co-deposited species. At 25 K, the neutral species is favoured over the zwitterionic form in non-polar environments, whereas for pure glycine, or in glycine/water mixtures, the dominant species is the latter. The conversion is easily followed by the weakening of two infrared bands in the mid-IR region, associated to the neutral structure. Theoretical calculations are performed on crystalline glycine and on molecular glycine, both isolated and surrounded by water. Spectra predicted from these calculations are in reasonable agreement with the experimental spectra, and provide a basis to the assignments. Different spectral features are suggested as probes for the presence of glycine in astrophysical media, depending on its form (neutral or zwitterionic), their temperature and composition.     

Synthesis of novel copolymer：Poly(p-dioxanone-co-L-phenylalanine)

In order to expand the application of poly(p-dioxanone) or PPDO in biomedical area,a series of novel copolymers were synthesized successfully by one-step,melted copolymerization of p-dioxanone(PDO) and L-phenylalanine N-carboxyanhydride(L-Phe-NCA) monomers.With the in-feed molar ratio of L-PheNCA /PDO equal to 1/20,the conversions of the two kinds of monomers were calculated from ~1H NMR. The average molecular weight and polydispersity of the copolymer increase with the increasing reaction time and catalyst concentration.However,the conversions of the two kinds of monomers did not change with the reaction conditions.A three-step mechanism is presented and proved by high resolution ~1H NMR and IR spectrums.     

Synthese de polymeres a proprietes pharmacologiques. Introduction de sequences peptidiques au sein de la chaine macromoleculaire

The introduction of peptidic sequences into polymers with pharmacological properties may increase the biocompatibility of the macromolecular prodrug. The synthesis of polypeptides from N-carboxyanhydrides bearing the active principles defines this objective. The l-lysine blocked as copper complex reacts with steroidic chloroformates (cholesterol-testosterone). After deblocking of the complex and treatment by phosgene, the corresponding N-carboxyanhydrides are obtained. Polymerization and copolymerization (with glycine N-carboxyanhydride) give oligopeptides bearing steroidic backbone as side-group. The low molecular weight of the synthesized compounds, the limited water solubility and the presence of secondary products limit the development of the method. Pharmacological tests are being undertaken to study delayed effects due to slow release of the steroid, to compare the biocompatibility of such prodrugs.     

Molecular Networks in Dynamic Multilevel Systems

Dynamic multilevel systems can be assembled from molecular building blocks through two or more reversible reactions that form covalent bonds. Molecular networks of dynamic multilevel systems can exhibit different connectivities between nodes. The design and creation of molecular networks in multilevel systems require control of the crossed reactivity of the functional groups (how to connect nodes) and the conditions of the reactions (when to connect nodes). In recent years, the combination of orthogonal and communicating reactions, which can be simultaneous or individually activated, has produced a variety of systems that have given rise to macrocycles and cages, as well as molecular motors and multicomponent architectures on surfaces. A given set of reactions can lead to systems with unique responsiveness, compositions, and functions as a result of the relative reactivities. In this Concept article, different molecular networks from synthetic systems that can be produced by combinations of different reaction types are discussed. Moreover, applications of this chemistry are highlighted, and future perspectives are envisioned.     

Hydrophobic hydration

The problem of interaction between organic and water moieties (neutral or ionized water molecular species) is of particular interest in chemistry in view of its implications to physico-chemical behavior of chemical and biological systems. Hydration patterns which result from interaction between hydrophilic and hydrophobic species are non trivial in chemistry. The key issue is that water molecules are able to aggregate in extremely large variety of structural modes. Tetrahedral geometry of intermolecular bonding around water molecule is analogous in geometrical terms to that of intramolecular geometry of carbon atom, known as a source of infinite number of organic structures. In general, space filling with hydrogen bonded water molecules is rather low. It may be illustrated in the following way: volume of neonium atoms is comparable to that of water molecules whilst having atomic mass just 10% higher than molecular mass of water. Thus, liquid neonium and liquid water would have similar densities if molecular packing is of comparable efficiency. The real values are much different, however. Liquid neonium at its boiling temperature has density of 1.20 g cm^–3 , thus displaying significantly denser packing that that of water molecules. It certainly means that solid or liquid water has a ‘porous’ structure and may lead to molecular inclusion of foreign (guest) species in the intermolecular space of water framework. This property is not that simple, however, since inclusion of foreign (guest) species is, as a rule, associated with rearrangement of the host framework structure [1]. Anyway, inefficient packing of the mono-component host solid phases may be considered as a prerequisite for its pronounced clathration ability.     

Effect of metal ions (Li+, Na+, K+, Mg2+, Ca2+, Ni2+, Cu2+, and Zn2+) and water coordination on the structure of glycine and zwitterionic glycine

Interactions between metal ions and amino acids are common both in solution and in the gas phase. Here, the effect of metal ions and water on the structure of glycine is examined. The effect of metal ions (Li+, Na+, K+, Mg2+, Ca2+, Ni2+, Cu2+, and Zn2+) and water on structures of Gly.Mn+(H2O)m and GlyZwitt.Mn+(H2O)m (m = 0, 2, 5) complexes have been determined theoretically by employing the hybrid B3LYP exchange-correlation functional and using extended basis sets. Selected calculations were carried out also by means of CBS-QB3 model chemistry. The interaction enthalpies, entropies, and Gibbs energies of eight complexes Gly.Mn+ (Mn+ = Li+, Na+, K+, Mg2+, Ca2+, Ni2+, Cu2+, and Zn2+) were determined at the B3LYP density functional level of theory. The computed Gibbs energies DeltaG degrees are negative and span a rather broad energy interval (from -90 to -1100 kJ mol(-1)), meaning that the ions studied form strong complexes. The largest interaction Gibbs energy (-1076 kJ mol(-1)) was computed for the NiGly2+ complex. Calculations of the molecular structure and relative stability of the Gly.Mn+(H2O)m and GlyZwitt.Mn+(H2O)m (Mn+ = Li+, Na+, K+, Mg2+, Ca2+, Ni2+, Cu2+, and Zn2+; m = 0, 2, and 5) systems indicate that in the complexes with monovalent metal cations the most stable species are the NO coordinated metal cations in non-zwitterionic glycine. Divalent cations Mg2+, Ca2+, Ni2+, Cu2+, and Zn2+ prefer coordination via the OO bifurcated bonds of the zwitterionic glycine. Stepwise addition of two and five water molecules leads to considerable changes in the relative stability of the hydrated species. Addition of two water molecules at the metal ion in both Gly.Mn+ and GlyZwitt.Mn+ complexes reduces the relative stability of metallic complexes of glycine. For Mn+ = Li+ or Na+, the addition of five water molecules does not change the relative order of stability. In the Gly.K+ complex, the solvation shell of water molecules around K+ ion has, because of the larger size of the potassium cation, a different structure with a reduced number of hydrogen-bonded contacts. This results in a net preference (by 10.3 kJ mol(-1)) of the GlyZwitt.K+H2O5 system. Addition of five water molecules to the glycine complexes containing divalent cations Mg2+, Ca2+, Ni2+, Cu2+, and Zn2+ results in a net preference for non-zwitterionic glycine species. The computed relative Gibbs energies are quite high (-10 to -38 kJ mol(-1)), and the NO coordination is preferred in the Gly.Mn+(H2O)5 (Mn+ = Mg2+, Ca2+, Ni2+, Cu2+, and Zn2+) complexes over the OO coordination.     

Peptide synthesis in aqueous environments: the role of extreme conditions and pyrite mineral surfaces on formation and hydrolysis of peptides

A comprehensive study of free energy landscapes and mechanisms of COS-mediated polymerization of glycine via N-carboxy anhydrides (NCAs, "Leuchs anhydrides") and peptide hydrolysis at the water-pyrite interface at extreme thermodynamic conditions is presented. Particular emphasis is set on the catalytic effects of the mineral surface including the putative role of the ubiquitous sulfur vacancy defects. It is found that the mere presence of a surface is able to change the free energetics of the elementary reaction steps. This effect can be understood in terms of a reduction of entropic contributions to the reactant state by immobilizing the reactants and/or screening them from bulk water in a purely geometric ("steric") sense. Additionally, the pyrite directly participates chemically in some of the reaction steps, thus changing the reaction mechanism qualitatively compared to the situation in bulk water. First, the adsorption of reactants on the surface can preform a product-like structure due to immobilizing and scaffolding them appropriately. Second, pyrite can act as a proton acceptor, thus replacing water in this role. Third, sulfur vacancies are found to increase the reactivity of the surface. The finding that the presence of pyrite speeds up the rate-determining step in the formation of peptides with respect to the situation in bulk solvent while stabilizing the produced peptide against hydrolysis is of particular interest to the hypothesis of prebiotic peptide formation at hydrothermal aqueous conditions. Apart from these implications, the generality of the studied organic reactions are of immediate relevance to many fields such as (bio)geochemistry, biomineralization, and environmental chemistry.     

On assembling polychlorinated aromatic hydrocarbons from carbon tetrachloride via dichlorocarbene intermediary by a solvothermal reaction: a reaction pattern from carbene-ylide interconversion

[reaction: see text] The forced one-electron reduction of carbon tetrachloride with sodium in a sealed steel vessel is shown to have a narrow window of conditions to arrest the reaction at the polychlorinated aromatic hydrocarbons (PCAHs), as well as to prevent the reaction from proceeding all the way to the final stage of graphite and other carbon solids. The intermediates are quenched with toluene or benzene to give electrophilic substitution products and with water to give a quinomethine as the major product. The product pattern leads us to propose the carbene, perchlorobenzo[c,d]pyren-6-ylidene, or its reversible dimer as the major intermediate among others, that survives the severe conditions until coming into contact with these nucleophiles. Mainly from aromatic resonance stabilization, the carbene is proposed to have a delocalized singlet state analogous to a ylide electronic structure and, thus, undergoes observed ionic reactions instead of typical carbene reactions. This work serves as a mechanistic link on the structural evolution of carbon networks between molecular chemistry and nanomaterial chemistry.     

Glycine at the pyrite-water interface: the role of surface defects

Ab initio molecular dynamics simulations were performed in order to study chemisorption, electronic properties, and desorption of glycine at wet pyrite surfaces focusing on the role of surface point defects. The change in the electronic structure and its influence on the chemical reactivity of the free FeS(2)(100) surface due to sulfur vacancies was studied in detail yielding several adsorption modes of glycine and water molecules. Energetically preferred adsorption modes were furthermore investigated in the presence of hot pressurized water mimicking "Iron Sulfur World" prebiotic conditions. The metadynamics Car-Parrinello technique was employed to map the free energy landscape including paths and barriers for desorption of glycine from such wet defective surfaces. The ubiquitous sulfur vacancies are found to increase the retention time of the adsorbed amino acid by many orders of magnitudes in comparison to the ideal pyrite-water interface. The importance of these findings in terms of a possible two-dimensional primordial chemistry on mineral surfaces is discussed.     

Molecular Shape Analysis of a Maillard Reaction Intermediate

Abstract

The Maillard (browning) reaction involving the polycondensation of sugars and amino acids is believed to be an important abiotic pathway for humic substance formation in nature. However, a major drawback is that the Maillard reaction is extremely slow at temperatures encountered under normal environmental conditions. In order to elucidate some details of this process molecular shape analysis was applied to investigate the initial reaction between D-glucose and glycine to form the Amadori compound fructosylglycine which is an intermediate product in the Maillard reaction. The structure of the Amadori compound was optimized at a quantum mechanical level and its ground state electron energy calculated. Molecular Iso-Density Contours (MIDCO's), electron density contour surfaces of constant electron density, were constructed for D-glucose, glycine and fructosylglycine in order to study the steric conditions for the reaction. The calculations indicate that the Amadori compound and water on one hand and the separate entities D-glucose and glycine on the other hand are very similiar to each other in terms of their ground state energy. This agrees with the experimental observation that the reaction between D-glucose and glycine to form the Amadori compound is slow.     

N-Heterocyclic carbene-mediated zwitterionic polymerization of N-substituted N-carboxyanhydrides toward poly(α-peptoid)s: kinetic, mechanism, and architectural control

N-Heterocyclic carbene (NHC)-mediated polymerizations of N-butyl N-carboxyanhydride (Bu-NCA) to produce cyclic poly(N-butyl glycine)s (c-NHC-PNBGs) have been investigated in various solvents with NHCs having differing steric and electronic properties. Control over the polymer molecular weight (MW) and polymerization rate is strongly dependent on the solvent and the NHC structure. Kinetic studies reveal that the propagating intermediates for the polymerization in low dielectric solvents (e.g., THF or toluene) maintain cyclic architectures with two chain ends in close contact through Coulombic interaction. The NHCs not only initiate the polymerization, but also mediate the chain propagation as intramolecular counterions. Side reactions are significantly suppressed in low dielectric solvents due to the reduced basicity and nucleophilicity of the negatively charged chain ends of the zwitterions, resulting in quasi-living polymerization behavior. By contrast, the two charged chain ends of the zwitterionic species are fully dissociated in high dielectric solvents. The chain propagation proceeds as in conventional anionic polymerizations, wherein side reactions (e.g., transamidation) compete with chain propagation, resulting in significantly diminished control over polymer MW. The cyclic zwitterionic propagating species can be converted into their linear polymeric analogues (l-NHC-PNBGs) by end-capping with electrophiles (e.g., acetyl chloride) or the NHC-free cyclic analogues (c-PNBGs) by treatment with NaN(TMS)(2), as evidenced by MALDI-TOF MS, NMR, and SEC analysis.     

New experimental and theoretical approach to the heterogeneous hydrolysis of NO2: key role of molecular nitric acid and its complexes

Although heterogeneous chemistry on surfaces in the troposphere is known to be important, there are currently only a few techniques available for studying the nature of surface-adsorbed species as well as their chemistry and photochemistry under atmospheric conditions of 1 atm pressure and in the presence of water vapor. We report here a new laboratory approach using a combination of long path Fourier transform infrared spectroscopy (FTIR) and attenuated total reflectance (ATR) FTIR that allows the simultaneous observation and measurement of gases and surface species. Theory is used to identify the surface-adsorbed intermediates and products, and to estimate their relative concentrations. At intermediate relative humidities typical of the tropospheric boundary layer, the nitric acid formed during NO2 heterogeneous hydrolysis is shown to exist both as nitrate ions from the dissociation of nitric acid formed on the surface and as molecular nitric acid. In both cases, the ions and HNO3 are complexed to water molecules. Upon pumping, water is selectively removed, shifting the NO(3-)-HNO3(H2O)y equilibria toward more dehydrated forms of HNO3 and ultimately to nitric acid dimers. Irradiation of the nitric acid-water film using 300-400 nm radiation generates gaseous NO, while irradiation at 254 nm generates both NO and HONO, resulting in conversion of surface-adsorbed nitrogen oxides into photochemically active NO(x). These studies suggest that the assumption that deposition or formation of nitric acid provides a permanent removal mechanism from the atmosphere may not be correct. Furthermore, a potential role of surface-adsorbed nitric acid and other species formed during the heterogeneous hydrolysis of NO2 in the oxidation of organics on surfaces, and in the generation of gas-phase HONO on local to global scales, should be considered.     

Why calcium inhibits magnesium-dependent enzyme phosphoserine phosphatase? A theoretical study

Mechanisms for the formation of the Schiff base from acetaldehyde and butylamine, glycine and phosphatidylethanolamine based on Dmol3/DFT calculations were realized. For the case of phosphatidylethanolamine, calculations were done under periodic boundary conditions, in an amine-phospholipid monolayer model with two molecules of phosphatidylethanolamine by cell. All models contained explicit aqueous solvent. In the three cases, a neutral amino group is used to model the nucleophilic attack on the carbonyl group of acetaldehyde, and water molecules form hydrogen bond networks. These networks were involved in the reactions by performing as proton-transfer carriers, important in some steps of reactions, and stabilizing reaction intermediates. In all the studied reactions, they take place in two steps, namely: (1) formation of a carbinolamine and (2) its dehydration to the Schiff base, being the dehydration the rate-determining step of the process, consistent with available experimental evidence for similar reactions. The main difference between the studied reactions is found in the value for relative free energy for the intermediates and transition states in the second step; these values are lower in the cases of glycine and phosphatidylethanolamine in comparison with butylamine, due the influence of their molecular environments. Based on the results, the aminophospholipid surface environment and carboxylic group of glycine may boost Schiff base formation via a neighboring catalyst effect.     

Sorption of hypoiodous acid on activated carbon

In spite of good adsorption characteristics of activated carbon for molecular iodine, from water solution, problems arising due to complexity of chemistry of iodine and hydrolysis as well as influences of other relevant factors in water solutions which easily change the equilibrium concentrations toward domination of species with lower absorbability. Sorption of hypoiodus acid as predominant chemical form of iodine in neutral and weak alkaline solution within the range of micro concentrations has been studied in great details. In the experiments sorption of hypoiodous acid from water solutions on activated carbon with surface area of 1000 m²/g, under static and dynamic conditions, has been performed. Isotherms on various temperatures (25°C, 50°C, 70°C) has been obtained. Parameters of the sorption are determined and mechanism of adsorption of hypoiodous acid molecules on activated carbon has been discussed.     

Physico-chemical processes in imidazolium ionic liquids

Among the various properties exhibited by ionic liquids (ILs)--especially those based on the imidazolium cation-their inherent ionic patterns, very low vapour pressure and pronounced self-organization in the solid, liquid and even in the gas phase are particularly interesting since this allows the use of these fluids as alternative and complementary media to classical organic solvents and water in many applications. Hence, reaction paths that involve charge-separated intermediates or transition states are accelerated--by lowering the activation barrier-in the presence of ILs when compared with those performed in classical organic solvents. It is also possible, for example, to observe, by electrochemical methods, transient species (ionic and radical) that are otherwise undetectible in water or in molecular organic solvents and to investigate the interactions and behaviour of molecular, biological and macromolecular species in solution using physical and chemical methods which require special conditions such as high-vacuum, and which have been traditionally limited to solid state chemistry.     

Insight into the mechanism of the asymmetric ring-opening aminolysis of 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane catalyzed by titanium/BINOLate/water system: evidence for the Ti(BINOLate)2-bearing active catalyst entities and the role of water

The mechanism of the enantioselective ring-opening aminolysis of 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane with benzylamine, catalyzed by the titanium-BINOLate species generated in situ from a mixture of enantiopure BINOL (1,1'-bi-2-naphthol), Ti(OiPr)4, and H2O in the presence of benzylamine in toluene, was investigated in detail using a combination of reaction profile measurements, nonlinear effect (NLE) studies, solution (1)H NMR analysis, electrospray ionization mass spectrometry (ESI-MS), as well as the results obtained from screening of dynamic catalyst library of complexes L(a)/Ti/L(b) (L(a) or L(b) = chiral diol ligands). The BINOL-to-titanium ratio and the presence or absence of water in the catalytic system were found to exert profound influences on both reactivity and enantioselectivity of the reaction. The NLE studies revealed that the titanium species involved in the catalysis should contain more than one BINOL unit, either within or at the periphery of the catalytic cycle. ESI-MS analysis of the catalytic systems provided strong support in favor of the mechanistic proposal that titanium complexes bearing the Ti(BINOLate)2 moiety should be the active species responsible for the catalysis, which was further confirmed by the observation of synergistic effect of the heteroligand combinations during screening of the dynamic catalyst library. ESI-MS analysis of the reaction system indicated that water does not take part in the catalyst generation, which is an unprecedented finding in contrast to the previous mechanistic understandings in the titanium catalytic chemistry involving the participation of water. Most probably, water functions as a proton shuttle in the catalysis, facilitating the proton transfer between the reactants. Furthermore, the origin of (+)-NLE observed in the present catalytic system is rationalized on the basis of the ESI-MS analysis of the catalyst system prepared from a 1:1 pseudoracemic mixture of (S)-BINOL and (R)-3,3',6,6'-D4-BINOL. Finally, the reactivity differences between several couples of epoxide/amine combinations were tentatively rationalized on the basis of the arguments on their relative coordination preferences, and several other aliphatic amines were also found to efficiently ring-open the titled epoxide in excellent enantioselectivities. The results from this study are expected to shed some light on the often elusive chemistry of Ti(IV)-based catalytic systems where water or molecular sieves (or alcohols, etc.) are found to play an important yet inexplicable role and may help the search for effective asymmetric Ti(IV) catalysts for other types of reactions.