The heterogeneously catalyzed epoxidation of alkenes is experimentally challenging, theoretically interesting, and technologically important. Although large-scale ethylene epoxidation is universally carried out with Ag catalysts, recent laboratory studies on single crystal surfaces show that Cu is intrinsically much more selective than Ag in the epoxidation of a variety of terminal alkenes. The reasons for this striking difference between Ag and Cu have been investigated by means of density functional theory. It is found that the fundamental cause is the inversion in the ordering of activation barriers for the competing pathways to epoxide formation versus acetaldehyde formation (the latter being the first step on the route to combustion). On Cu, epoxide formation is less activated than aldehyde formation; the opposite is true on Ag. This behavior is associated with a late transition state to epoxidation on Cu (i.e., product-like) compared to an early (reactant-like) transition state to epoxidation on Ag.

A highly enantioselective cyanohydrin synthesis with aromatic aldehydes using chiral lithium binaphtholate aqua or alcohol complexes has been developed and is a simple and inexpensive catalyst suitable for process chemistry to give gram-scale cyanohydrins successfully. Dramatic improvements in enantiomeric excess have been realized along with an interesting changeover in absolute stereochemistry of cyanohydrin product against the thoroughly “dry” catalytic systems.

Intermolecular proton transfer in solid phase from the hydroxo bridge to a water molecule occurs in a new μ-hydroxo iron(III) compound of formula {EtNH₃[Fe₂(ox)₂Cl₂(μ-OH)]·2H₂O}_n leading to a still crystalline compound in which the μ-oxo bridge replaces the μ-hydroxo one. Both three-dimensional compounds exhibit magnetic ordering at T_c ca. 70 K due to a spin canting.

The recent observation of photoinduced radical pairs comprising a flavin radical and an oxidized amino acid residue in various blue-light-sensitive proteins has highlighted the need to gain a more complete understanding of the electronic structure of flavin radicals. In particular, precise knowledge of the anisotropy of the Zeeman interaction quantified by the g-tensor is necessary for attaining an unambiguous identification of flavin radicals by electron paramagnetic resonance (EPR). In a recent study of a protein-bound neutral flavin radical, we have determined the principal values of the g-tensor using high-frequency/high magnetic field EPR performed at 360 GHz/12.8 T. However, in those experiments, the orientation of the principal axes of g could not be unambiguously established with respect to the molecular frame of the isoalloxazine moiety. In this contribution we resolve this ambiguity by pulsed electron−nuclear double resonance (ENDOR) at 95 GHz/3.5 T (W-band). At such high values of the microwave frequency and the magnetic field, the g anisotropy provides improved spectral resolution compared to an ENDOR experiment performed at conventional 9.5 GHz/0.35 mT (X-band). This enables one to utilize Zeeman magnetoselection to obtain single-crystal-like data from disordered samples in frozen solution. Experiments exploiting this orientation selection have allowed us to use the hyperfine coupling of the methyl protons at C(8α) of the isoalloxazine ring to determine the angle between the molecular frame and the principal axes of g. Quite surprisingly, the g-tensor in FADH^• is not oriented as one would have expected for a 1,3-semibenzoquinone radical. For the latter, the X-axis of g commonly bisects the smaller angle between the two axes along the CO bonds. In FADH^•, the large spin density on N(5) and C(4a) apparently contributes to a significant (44°) reorientation of the g-tensor axes.

We describe a general methodology for the direct detection of DNA by the design of a split-protein system that reassembles to form an active complex only in the presence of a targeted DNA sequence. This approach, called SEquence Enabled Reassembly (SEER) of proteins, combines the ability to rationally dissect proteins to construct oligomerization-dependent protein reassembly systems and the availability of DNA binding Cys₂-His₂ zinc-finger motifs for the recognition of specific DNA sequences. We demonstrate the feasibility of the SEER approach utilizing the split green fluorescent protein appended to appropriate zinc fingers, such that chromophore formation is only catalyzed in the presence of DNA sequences that incorporate binding sites for both zinc fingers.

A family of simple pyrimidine analogues has been synthesized, and their photophysical properties have been investigated. The most responsive of the family was incorporated in DNA. This isosteric fluorescent DNA analogue monitors denaturation of a DNA duplex via fluorescence and positively detects the presence of abasic sites in DNA duplexes.

Stacked thin layers of silver alloy (AgPdCu) and MoCr layers on 10 × 15 cm² glass substrates were patterned by microcontact wave printing and etching. Patterns of etch-resistant octadecanethiol self-assembled monolayers (SAMs) were wave printed with regular backplane stabilized PDMS stamps. Pattern development was achieved by etching both metal layers in a single step, employing a nitric acid-based etching bath. Trifluoroacetic acid and a nitrite salt were identified as essential bath components for a homogeneous etching process. Etch defects could be eliminated by the addition of a decanesulfonate, which stabilizes the SAM resist via a defect healing mechanism.

The advent of scanning tunneling microscopy (STM) has permitted a detailed atomic view of organic molecules adsorbed on solid surfaces. In this work, we make use of the STM to provide an unprecedented direct single-molecule perspective on the cis−trans photoisomerization of stilbene molecules within ordered monolayers physisorbed on the Ag/Ge(111)−(√3×√3)R30° surface. The STM view of the molecular structure transformation upon irradiation provides direct evidence for the generally accepted one-bond-flip mechanism proposed for the photoisomerization process. We also find that the surface environment produces a profound effect on the reaction mechanism. The reaction is observed to proceed mainly through pairs of co-isomerizing molecules situated at domain boundaries. To explain these observations, we propose a mechanism whereby excitation migrates to the domain boundary and the reaction occurs through a biexciton reaction pathway.

Aqueous polyoxometalate (H₃PMo₁₂O₄₀) solution reduced by CO with liquid water using gold nanoparticle catalysts at room temperature, which contains protons in liquid water and electrons associated with the reduced polyoxometalate, can produce gaseous H₂ or can hydrogenate benzene over an electrochemical cell consisting of a simple carbon anode, a proton-exchange membrane, and a Pt- or Rh-based cathode. In the present cell, H₂ can be produced from the reduced H₃PMo₁₂O₄₀ solution at voltages that are lower by about 1.15 V compared to water electrolysis.

Hollow zeolite architectures on different length scales have been obtained upon controlled desilication of Al-zoned ZSM-5 zeolites in alkaline medium. The hollow ZSM-5 crystals possess a functional Al-rich exterior and a tunable internal porosity and accessibility.

By employing a novel low-temperature synthetic pathway, highly ordered cubic mesoporous materials with hitherto the largest pores (up to 27 nm) and unit cells (up to 44 nm) have been successfully obtained.

The emission of the DNA light-switch complex [Ru(bpy)₂(tpphz)]²⁺ (bpy = 2,2‘-bipyridine, tpphz = tetrapyrido[3,2-a:2‘,3‘-c:3‘ ‘,2‘ ‘-h:2‘ ‘‘,3‘ ‘‘-j]phenazine) can be reversibly turned ON and OFF over several cycles. The tpphz and taptp (taptp = 4,5,9,18-tetraazaphenanthreno[9,10-b] triphenylene) ligands in [Ru(bpy)₂(tpphz)]²⁺ and [Ru(bpy)₂(taptp)]²⁺, respectively, intercalate between the DNA bases, and a 50-fold increase in emission intensity of [Ru(bpy)₂(tpphz)]²⁺ is observed upon DNA intercalation. The [Ru(bpy)₂(tpphz)]²⁺ DNA light switch can be turned OFF statically in the presence of Co²⁺, Ni²⁺, and Zn²⁺, and the emission can be fully restored by the addition of EDTA. Cycling of the DNA light switch OFF and ON can be accomplished through the successive introduction of Co²⁺ and EDTA, respectively, to solutions of DNA-bound [Ru(bpy)₂(tpphz)]²⁺. Owing to the absence of additional coordination sites, the emission of DNA−intercalated [Ru(bpy)₂(taptp)]²⁺ is not quenched by transition metal ions in solution. To our knowledge, this work presents the first example of a reversible DNA light switch.

Intracellular signal transduction relies on spatial and temporal signal transmitter dynamics. To clarify the correlations of these transmitter molecules, multicolor-imaging has been widely used. However, in the case of applying multiple indicators in a cell, spectral overlap of the indicators prevents accurate quantitative analysis. Moreover, the invasive (toxic) effect, the localization, the metabolism, as well as photobleaching of these indicators complicate the situation. Here, we show that single-molecular multifluorescent probes can overcome these problems. While intracellular calcium plays a critical role as a signal transmitter and magnesium acts as a cofactor in many situations, the correlations between the two cations are now the main issue. We designed and synthesized a Ca²⁺−Mg²⁺ responsive multifluorescent probe, KCM-1. KCM-1 shows a spectral blue shift upon complexation to Ca²⁺ and a red shift to the presence of Mg²⁺. With data analyzed at different excitation wavelengths, the concentrations of Ca²⁺ and Mg²⁺ are simultaneously quantified. Furthermore, by using the AM-ester method, intracellular Ca²⁺ and Mg²⁺ concentrations are simultaneously imaged. Such a type of intracellular multiple analyte imaging by a single-molecular multifluorescent probe is successfully demonstrated for the first time.

Two molecules of planar M^II(acac)₂ complexes (M = Pt, Pd, and, Cu; acac = acetylacetonato) are efficiently stacked within an organic-pillared coordination cage, exhibiting characteristic spectroscopies (for M = Pt and Pd) and electron spin−spin coupling (for M = Cu) attributable to metal−metal interaction.

Two unique helical zinc gallate (ZnGa₂O₄) nanostructures were synthesized by thermal evaporation using the zinc selenide (ZnSe) nanowires; helical ZnGa₂O₄ nanowire rolls either on a straight ZnSe nanowire support or without any support. They all consist of single-crystalline cubic ZnGa₂O₄ crystals without any dislocation over the entire helical structure and have four equivalent growth directions of 〈011〉 with the axial direction of [001]. We suggest that the lattice matching with the ZnSe nanowires would be an important factor in determining the growth direction of the helical ZnGa₂O₄ nanowires.

CuBr₂-catalyzed three-component coupling of N-benzylallylamine, ethyl glyoxalate, and terminal alkynes afforded glycine-tethered 1,6-enynes, which were further transformed into polycyclic pyrrole-2-carboxylates via novel cycloisomerization/Diels−Alder cycloaddition/dehydrogenation sequence under iridium-catalyzed conditions.

By simply supporting carbon nanotubes with a metal substrate of a redox potential lower than that of the metal ions to be reduced into nanoparticles, we have developed a facile yet versatile and effective substrate-enhanced electroless deposition (SEED) method for functionalizing nanotubes with a large variety of metal nanoparticles, including those otherwise impossible by more conventional electroless deposition methods, in the absence of any additional reducing agent. The nanotube-supported metal nanoparticles thus produced are electrochemically active, and the newly developed SEED process represents a significant advance in functionalization of carbon nanotubes with metal nanoparticles for a wide range of potential applications, including in advanced sensing and catalytic systems.

A new synthetic path, far superior to either of those previously available, to the W₂(hpp)₄ molecule (Hhpp = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine) is reported. The reaction of W(CO)₆ with Hhpp in o-dichlorobenzene at 200 °C produces W₂(hpp)₄Cl₂ in a one-pot reaction in over 90% yield. This compound is stable and easily stored for further use, and it can be efficiently reduced in a one-step reaction to the title compound W₂(hpp)₄.

Capillary NMR spectroscopy (CapNMR) was used to characterize 13 new cardenolides and related steroids from a severely mass-limited natural products sample derived from a rare firefly, Lucidota atra. These analyses were carried out on only partially purified samples, each containing 20−100 μg of up to three steroids. Compared to other NMR spectroscopic techniques, CapNMR provided an up to 3-fold gain in sensitivity while maintaining very high spectral quality, which was essential for the identification of the L. atra steroids. We show that CapNMR allows for routine ¹H and ¹³C NMR spectroscopic characterization of small molecule samples containing as little as 40 nmol of material.

Selective epoxidation of cinnamates versus crotonate was used to detect hydrophobic binding of the cinnamates in the transition states with hydrophobic oxidizing agents in water solution. With peracids as oxidants, no such effect was seen, in accord with the calculated geometries of epoxidation in which the hydrophobic groups of substrate and oxidant could not stack. However, with oxaziridinium salts carrying fused benzene rings there was significantly high selectivity for the cinnamates in water solution, which could be suppressed with added 2-propanol. The hydrophobically induced selectivity changes were even larger, in free energy terms, than those reported previously for the atom-transfer reactions in hydride reductions. Furthermore, the oxaziridinium ions could be generated with oxone from catalytic amounts of the corresponding iminium salts. These substrate selectivities should also carry over to positional selectivities in polyenes.

The first spectroscopic evidence for the existence of the HBX and DBX (X = F, Cl, Br) free radicals has been obtained from laser-induced fluorescence and wavelength-resolved emission spectra. The vibrational frequencies measured in emission are in excellent agreement with our ab initio (CCSD(T)/aug-cc-pVTZ) predictions. The patterns of resolved rotational sub-band structure and deuterium isotope effects have been used to positively identify the radicals. The experimental data and ab initio predictions will be useful in searches for the matrix infrared and microwave spectra of these new radicals.

The enantioselective addition of β-ketoesters to unsaturated N-acylthiazolidinethiones catalyzed by Ni(II) Tol-BINAP Lewis acid complexes is reported. Notable features of this reaction are its operation simplicity, the obviated need for the addition of an external base, and the ease with which the adducts are converted into a range of potentially useful derivatives. In particular, the dihydropyrone adducts are versatile scaffolds for further stereoselective elaboration.

A highly stereoselective total synthesis of (+)-asimicin (1) is reported. The synthesis features two chelate-controlled [3 + 2] annulation reactionsone of which (e.g., 2 + 3) constitutes a key, convergent fragment assembly stepthat establish all of the stereochemistry of the bis-tetrahydrofuran unit of the natural product.

Rate studies of the addition of n-BuLi in the presence of TMEDA to potentially chelating aldimines are consistent with a combination of monomer- and dimer-based mechanisms. Using mixtures of TMEDA and Et₂O reveals cooperative solvation in which both Et₂O and TMEDA coordinate to lithium at the monomer- and dimer-based transition structures. The four discrete mechanisms are affiliated with markedly different stereochemistries of the 1,2-addition.

This contribution describes the synthesis of gold nanorod (Au NR)/single-wall carbon nanotube (SWCNT) heterojunctions assembled directly on Si/SiO_x substrates. SWCNTs are attached to amine-functionalized Si/SiO_x substrates, and Au monolayer-protected clusters (MPCs) are adsorbed to the surface of SWCNTs through hydrophobic interactions. Seed-mediated reduction of HAuCl₄ with ascorbic acid in the presence of cetyltrimethylammonium bromide (CTAB) onto the Au MPCs leads to the growth of larger Au nanostructures directly on the SWCNTs. Au NRs account for 19% of the nanostructures, some of which are attached directly to the sidewall and some at the ends of the SWCNTs. Raman spectroscopic measurements of SWCNTs before and after growth of the Au nanostructures reveal that the presence of Au leads to an approximately 50-fold enhancement of the Raman scattering signal. Combining 1D nanostructures of different materials (Au and carbon in this example) is of fundamental interest and may find use in nanoelectronics, chemical sensing, electrochemical, and spectroscopy applications.

We report 1H-1,2,3-triazole as an active group to dramatically enhance proton conduction in a polymer electrolyte membrane (PEM). The conductivities of a poly(4-vinyl-1H-1,2,3-triazole) membrane without any acidic dopants are about 10⁵ times greater than those of poly(4-vinylimidazole) in dry air at 50−150 °C. Polymers with groups promoting proton conduction attached to the backbone have great potential to offer excellent mechanical properties and long-term stability. Further, 1H-1,2,3-triazole and PEMs containing 1H-1,2,3-triazole are stable in a wide potential range, implying excellent electrochemical stability under fuel cell operating conditions.

Reaction of Sn(IV) with phosphonic acids results in the formation of tin phosphonates with a spherical morphology arising from the aggregation of nanosized individual particles. Under high magnification, the spheres are shown to be porous with surface areas of 200−515 m²/g, depending on the type of phosphonic acid and the synthesis conditions used. The pores are largely micro in nature but also somewhat dependent on the type of phosphonic acid utilized in the preparation. Both aliphatic and aromatic organic phosphonates form these spherical aggregates. Functional groups, such as amino and carboxyl, may be introduced as part of the phosphonic acid or subsequently by further reaction, leading to a large family of naturally formed nanoparticles with accompanying microporosity.

At the active site of urease, urea undergoes nucleophilic attack by water, whereas urea decomposes in solution by elimination of ammonia so that its rate of spontaneous hydrolysis is unknown. Quantum mechanical simulations have been interpreted as indicating that urea hydrolysis is extremely slow, compared with other biological reactions proceeding spontaneously, and that urease surpasses all other enzymes in its power to enhance the rate of a reaction. We tested that possibility experimentally by examining the hydrolysis of 1,1,3,3-tetramethylurea, from which elimination cannot occur. In neutral solution at 25 °C, the rate constant for the uncatalyzed hydrolysis of tetramethylurea is 4.2 × 10^-12 s^-1, which does not differ greatly from the rate constants observed for the uncatalyzed hydrolysis of acetamide (5.1 × 10^-11 s^-1) or N,N-dimethylacetamide (1.8 × 10^-11 s^-1) under the same conditions. We estimate that the proficiency of urease as a catalyst, (k_cat/K_m)/k_non, is 8 × 10¹⁷ M^-1, slightly higher than the values for other metalloenzymes (carboxypeptidase b and cytidine deaminase) that catalyze the hydrolysis of similar bonds.

Growing evidence indicates that endogenously produced hydrogen peroxide acts as a cellular signaling molecule that (among other things) can regulate the activity of some protein phosphatases. Recent X-ray crystallographic studies revealed an unexpected chemical transformation underlying the redox regulation of protein tyrosine phosphatase 1B, in which oxidative inactivation of the enzyme yields an intrastrand protein cross-link between the catalytic cysteine residue and its neighboring amide nitrogen. This work describes a small organic molecule that serves as an effective model for the redox-sensing assembly of functional groups at the active site of PTP1B. Findings obtained using this model system suggest that the oxidative transformation of PTP1B to its “crosslinked” inactive form can proceed directly via oxidation of the active-site cysteine to a sulfenic acid (RSOH). The remarkably facile nature of this protein cross-link-forming reaction, along with the widespread cellular occurrence of protein sulfenic acids generated via oxidation of cysteine residues, suggests that the type of oxidative protein cross-link formation first seen in the context of PTP1B represents a potentially general mechanism for redox “switching” of protein function. Thus, the chemistry characterized here could have broad relevance to both redox-regulated signal transduction and the toxic effects of oxidative stress.

There is currently considerable interest in the phenomenon of polymorphism in organic molecular solids, and a key issue in this field is to understand the experimental techniques and procedures that may be employed to obtain new polymorphic forms of a given molecule. This paper demonstrates that the polymorphic form of a material (sodium acetate) obtained by a solid-state dehydration process (starting from sodium acetate trihydrate) can be altered by carrying out the dehydration process under conditions of rapid (several kilohertz) sample rotation in a solid-state magic-angle-spinning NMR probe. This observation suggests a new opportunity to influence the outcome of solid-state dehydration/desolvation processes and, in particular, to alter the polymorphic form of the product obtained.

The intramolecular Diels−Alder reaction of allenic ketones containing a furyl unit (IMDAF) to generate oxatricyclic systems in good yields is described. The alkene dienophiles 1ab give poor yields of the cycloadducts 2ab, presumably due to the facile retro Diels−Alder reaction. However, the analogous allenic dienophile 7 afforded the desired cycloadduct 8 in 91% yield on treatment with dimethylaluminum chloride. When the allene bears an alkyl substituent on the terminal carbon, complete diastereoselectivity is seen in the IMDAF, e.g. cyclization of 14 gave only the cycloadduct 15 in 80% yield presumably due to greater steric hindrance in the transition state II as compared to that in I. Finally we report complete chirality transfer of the stereochemistry of an allene to the carbon framework of the oxatricyclic system. Thus, the optically active allenic ketone 20 afforded only the desired cycloadduct 21 with the correct absolute stereochemistry needed for the synthesis of the arisugacin class of natural products.

A new method for intermolecular sp³−sp³ C−C bond formation between primary aliphatic alcohol and olefin by use of a RhCl(PPh₃)₃ (cat.)/BF₃·OEt₂ (2.5 equiv)/BuBr (0.5 equiv)/toluene system was first disclosed, which possessed quite significant utilities for organic synthesis, especially for that of secondary alcohols. The most significant aspect is the discovery that rhodium-catalyzed C−H bond activation of alcohols is feasible under Lewis acid-promoted conditions.

Crystallographic examination of [μ₃-S(AuCNC₇H₁₃)₃](SbF₆) shows that it undergoes a reversible phase change from orthorhombic to monoclinic upon cooling. At 190 K, the structure shows that two cations self-associate to form a pseudo-octahedral array of six gold atoms connected by both intra- and interionic aurophilic interactions. On cooling, the clusters become less symmetric, and in one, the interionic Au···Au separations increase, while they decrease in the second cluster. The luminescence of crystalline [μ₃-S(AuCNC₇H₁₃)₃](SbF₆) shows corresponding changes in emission, with two emissions of similar lifetimes but with different excitations at 77 K, but only a single emission at 298 K. In contrast, [μ₃-S(AuCNC₆H₁₁)₃](PF₆), which has a similar structure to that of the high-temperature form of [μ₃-S(AuCNC₇H₁₃)₃](SbF₆), does not undergo a phase change or change in its luminescence upon cooling.

An efficient, environmentally benign method for the preparation of esters from alcohols under mild, neutral conditions without the need for carboxylic acid derivatives and condensing agents was developed. Catalyst design, based on new Ru(II) hydrido carbonyl complexes incorporating electron-rich PNP and PNN ligands has resulted in the novel complex (I) which is an outstanding catalyst for the dehydrogenation of primary alcohols to esters and H₂ under neutral conditions.

To avoid the toxic effects of both essential and nonessential metal ions, cells elaborate a variety of metal ion trafficking proteins that regulate metal ion mobility. While structures of several trafficking proteins have been determined, kinetic characterization of metal ion transfer between cognate protein partners and the factors controlling transfer has lagged behind, in part due to a limitation on methods to monitor the rapid transfer. In this Communication we report studies on the kinetics of Hg²⁺ transfer between separately expressed components of the flavoenzyme mercuric ion reductase (MerA) that take advantage of the sensitivity of the flavin fluorescence to the charge state of a cysteine thiol in the Hg²⁺ binding pathway. The thiolate form of C558 in the Tn501 MerA partially quenches the fluorescence of the oxidized enzyme. Protonation or binding of Hg²⁺ to the thiolate increases the fluorescence, providing a sensitive probe for kinetic analysis of the Hg²⁺ binding reaction. The kinetics of Hg²⁺ transfer in both directions between the cysteine pair of the separately expressed N-terminal domain and the C-terminal cysteines (C558, C559) of the catalytic core are presented, along with a model describing the overall process.

Three quadrupolar oligophenylenevinylenes with five rings in the conjugated backbone, terminal donor groups, and various acceptors and/or donors along the backbone were synthesized and their two-photon spectroscopic properties investigated. These chromophores exhibit large two-photon absorption cross sections over a wide wavelength range and two distinct peaks, the strongest of which (δ_max > 3600 GM) is observed at 960−970 nm, a wavelength close to twice the value of the linear absorption maximum (2λ⁽¹⁾_max). The findings on these chromophores are compared with those for analogous molecules with shorter conjugation length, for which the main two-photon band is at significantly shorter wavelength than 2λ⁽¹⁾_max.

The four-coordinate compound [(^tBu₂PCH₂SiMe₂)₂N]RuCH₃ undergoes rapid double H−C(sp³) activation at −78 °C to generate a “hydrido-carbene” complex. DFT calculations suggest that the origin of the low barrier to methane elimination is an α-agostic interaction in the low-lying singlet state of the highly unsaturated (PNP)RuMe. The hydrido−carbene complex can be viewed as a “masked” resting state of the four-coordinate cyclometalated alkyl complex, [(^tBu₂PCH₂SiMe₂)N(Me₂SiCH₂P(^tBu)(C(CH₃)₂CH₂)]Ru, where hydride migration from metal to carbon occurs before any subsequent reactivity.

High-field, heteronuclear NMR spectroscopy of biological macromolecules in native cellular environments is limited by the low concentrations present and the long data acquisition times needed for the experiments. Successful 1D and 2D heteronuclear NMR data have been reported, but the 3D experiments conventionally used for protein assignment and detailed characterization are generally too long to maintain cell viability. Here we describe the successful in vivo implementation of a suite of fast 3D NMR experiments which we have used to generate the complete backbone assignment of resonances in the recombinant polypeptide GB-1 within Escherichia coli cells. The data were acquired at 600 MHz with a cold probe using the projection reconstruction experiments, (3,2)HNCA, (3,2)HNCO, and (3,2)HA(CA)NH.

A general route to enantioenriched 3,3-diarylpropanals is presented. These useful building blocks are prepared via an asymmetric rhodium-catalyzed conjugate addition of arylboronic acids to cinnamaldehyde derivatives in the presence of chiral dienes. The addition of both electron-poor as well as electron-rich boronic acids proceeds smoothly with various enals in 63−90% yield with high enantioselectivities (89−93% ee).

The synthesis and isolation of 12 α-aryl, β, β‘-disilyl-substituted vinyl cations 1b−l, 7, and 8 with the tetrakis(pentafluorophenyl)borate counteranion is reported. The vinyl cations are characterized by NMR spectroscopy and are identified by their specific NMR chemical shifts (δ ¹³C(C⁺) = 178.1−194.5; δ ¹³C(C^β) = 83.3−89.9; δ ¹³C(C^ipso) = 113.6−115.2; δ ²⁹Si = 25.0−12.0), supported by density functional calculations at the B3LYP/6-311G(2d,p)//B3LYP/6-31G(d) level. All cations are found to be stable at room temperature in solution and in the solid state. The NMR chemical shifts as well as J-coupling data indicate for vinyl cations, 1b−l, 7, and 8, the occurrence of substantial stabilization through π-resonance via the aryl substituents and through σ-delocalization via the β-silyl groups. For vinyl cation 8, the free enthalpy of stabilization via π-resonance by the α-ferrocenyl substituent is determined by temperature-dependent ²⁹Si NMR spectroscopy to be ΔG^⧧ = (48.9 ± 4.2) kJ mol^-1. A Hammett-type analysis, which relates the ¹J(SiC^β) coupling constant and the low-field shift of the ²⁹Si NMR signal upon ionization, Δδ ²⁹Si, with the electron-donating ability of the aryl group, indicates an inverse relation between the extent of Si−C hyperconjugation and π-donation. The computed structures (at B3LYP/6-31G(d)) of the vinyl cations 1a−l, 7, and 8 reveal the consequences of Si−C hyperconjugation and of π-resonance interactions with the aryl groups. The structures, however, fail to express the interplay between σ-delocalization and π-conjugation in that the calculated Si−C bond lengths and the C⁺-C^ipso bond lengths do not vary as a function of the substituent.

The oxidation of methanol to formaldehyde on silica supported vanadium oxide is studied by density functional theory. For isolated vanadium oxide species silsesquioxane-type models are adopted. The first step is dissociative adsorption of methanol yielding CH₃O(O)V(O)₂ surface complexes. This makes the OV(OCH₃)₃ molecule a suited model system. The rate-limiting oxidation step involves hydrogen transfer from the methoxy group to the vanadyl oxygen atom. The transition state is biradicaloid and needs to be treated by the broken-symmetry approach. The activation energies for OV(OCH₃)₃ and the silsesquioxane surface model are 147 and 154 kJ/mol. In addition, the (OV(OCH₃)₃)₂ dimer (a model for polymeric vanadium oxide species) and the OV(OCH₃)₃^•+ radical cation are studied. For the latter the barrier is only 80 kJ/mol, indicating a strong effect of the charge on the energy profile of the reaction and questioning the significance of gas-phase cluster studies for understanding the activity of supported oxide catalysts.

Synthetic pathways to (salcy)CoX (salcy = N,N ‘-bis(3,5-di-tert-butylsalicylidene)-1,2-diaminocyclohexane; X = halide or carboxylate) complexes are described. Complexes (R,R)-(salcy)CoCl, (R,R)-(salcy)CoBr, (R,R)-(salcy)CoOAc, and (R,R)-(salcy)CoOBzF₅ (OBzF₅ = pentafluorobenzoate) are highly active catalysts for the living, alternating copolymerization of propylene oxide (PO) and CO₂, yielding poly(propylene carbonate) (PPC) with no detectable byproducts. The PPC generated using these catalyst systems is highly regioregular and has up to 99% carbonate linkages with a narrow molecular weight distribution (MWD). Inclusion of the cocatalysts [PPN]Cl or [PPN][OBzF₅] ([PPN] = bis(triphenylphosphine)iminium) with complex (R,R)-(salcy)CoCl, (R,R)-(salcy)CoBr, or (R,R)-(salcy)CoOBzF₅ results in remarkable activity enhancement of the copolymerization as well as improved stereoselectivity and regioselectivity with maximized reactivity at low CO₂ pressures. In the case of [PPN]Cl with (R,R)-(salcy)CoOBzF₅, an unprecedented catalytic activity of 620 turnovers per hour is achieved for the copolymerization of rac-PO and CO₂, yielding iso-enriched PPC with 94% head-to-tail connectivity. The stereochemistry of the monomer and catalyst used in the copolymerization has dramatic effects on catalytic activity and the PPC microstructure. Using catalyst (R,R)-(salcy)CoBr with (S)-PO/CO₂ generates highly regioregular PPC, whereas using (R)-PO/CO₂ with the same catalyst gives an almost completely regiorandom copolymer. The rac-PO/CO₂ copolymerization with catalyst rac-(salcy)CoBr yields syndio-enriched PPC, an unreported PPC microstructure. In addition, (R,R)-(salcy)CoOBzF₅/[PPN]Cl copolymerizes (S)-PO and CO₂ with a turnover frequency of 1100 h^-1, an activity surpassing that observed in any previously reported system.

The factors controlling the highly α-selective C-glycosylation of ribose derivatives were determined by examining the stereoselective reactions of 18 ribose analogues differing in substitution at C-2, C-3, and C-4. The lowest energy conformers of the intermediate oxocarbenium ions display the C-3 alkoxy group in a pseudoaxial orientation to maximize electrostatic effects. To a lesser extent, the C-2 substituent prefers a pseudoequatorial position, and the alkyl group at C-4 has little influence on conformational preferences. In all cases, the product was formed by stereoelectronically preferred inside attack on the lowest energy conformer.

Two electrochemical oxidation waves assigned to the D_5h isomer of Sc₃N@C₈₀ have been identified, and a 270-mV difference in the first electrochemical oxidation potentials of the I_h and D_5h isomers has been measured. On the basis of this oxidative potential difference, a strategy for isomeric purification involving a selective chemical oxidation of the D_5h isomer is reported. Variable scan cyclic voltammetry of the resultingly pure Sc₃N@C₈₀ I_h isomer shows evidence of a rapid endohedral chemical reaction following the first reduction process.

Dual quantum systems, 0-dimensional quantum dot, and 2-dimensional quantum wells were constructed in one II−VI semiconductor nanocrystal by the epitaxial growth of a barrier (ZnS) layer between the systems in solution. By alteration of the thickness of the barrier layer, the two quantum systems were controlled to either electronically coupled or decoupled. Evidence of optical coupling between the two band gap emissions was also observed. The position and relative intensity of the two emissions can be independently tuned by reaction conditions. Total photoluminescence quantum efficiency of the dual emitting bands reached as high as 30% at room temperature under synthetic conditions not optimized for high emission.

The thermodynamic and structural characteristics of Al(C₆F₅)₃-derived vs B(C₆F₅)₃-derived group 4 metallocenium ion pairs are quantified. Reaction of 1.0 equiv of B(C₆F₅)₃ or 1.0 or 2.0 equiv of Al(C₆F₅)₃ with rac-C₂H₄(η⁵-Ind)₂Zr(CH₃)₂ (rac-(EBI)Zr(CH₃)₂) yields rac-(EBI)Zr(CH₃)⁺H₃CB(C₆F₅)₃^- (1a), rac-(EBI)Zr(CH₃)⁺H₃CAl(C₆F₅)₃^- (1b), and rac-(EBI)Zr²⁺[H₃CAl(C₆F₅)₃]^-₂ (1c), respectively. X-ray crystallographic analysis of 1b indicates the H₃CAl(C₆F₅)₃^- anion coordinates to the metal center via a bridging methyl in a manner similar to B(C₆F₅)₃-derived metallocenium ion pairs. However, the Zr−(CH₃)_bridging and Al−(CH₃)_bridging bond lengths of 1b (2.505(4) Å and 2.026(4) Å, respectively) indicate the methyl group is less completely abstracted in 1b than in typical B(C₆F₅)₃-derived ion pairs. Ion pair formation enthalpies (ΔH_ipf) determined by isoperibol solution calorimetry in toluene from the neutral precursors are −21.9(6) kcal mol^-1 (1a), −14.0(15) kcal mol^-1 (1b), and −2.1(1) kcal mol^-1 (1b→1c), indicating Al(C₆F₅)₃ to have significantly less methide affinity than B(C₆F₅)₃. Analogous experiments with Me₂Si(η⁵-Me₄C₅)(t-BuN)Ti(CH₃)₂ indicate a similar trend. Furthermore, kinetic parameters for ion pair epimerization by cocatalyst exchange (ce) and anion exchange (ae), determined by line-broadening in VT NMR spectra over the range 25−75 °C, are ΔH^⧧_ce = 22(1) kcal mol^-1, ΔS^⧧_ce = 8.2(4) eu, ΔH^⧧_ae = 14(2) kcal mol^-1, and ΔS^⧧_ae = −15(2) eu for 1a. Line broadening for 1b is not detectable until just below the temperature where decomposition becomes significant (∼75−80 °C), but estimation of the activation parameters at 72 °C gives ΔH^⧧_ce ≈ 22 kcal mol^-1and ΔH^⧧_ae ≈ 16 kcal mol^-1, consistent with the bridging methide being more strongly bound to the zirconocenium center than in 1a.

Fluorescence microscopy was used to study the folding transition of giant DNAs, T4 DNA (ca. 166 kbp), and λ DNA (ca. 48 kbp), which proceeds through intermediates with intramolecular segregation induced by pteridine−polyamine conjugates, i.e., 2-amino-6,7-dimethyl-4-(4,9,13-triazatridecylamino)pteridine and -4-(3-(aminopropyl)amino)pteridine. According to the results of DNA denaturation, UV and fluorescent spectroscopy, and transmission electron microscopic observations, it became clear that DNA folding induced by the polyamine derivative is not a continuous shrinking process but a combination of discontinuous processes.

The decomposition of S-nitrosothiols (RSNO) in solution under oxidative conditions is significantly faster than can be accounted for by homolysis of the S−N bond. Here we propose a cationic chain mechanism in which nitrosation of nitrosothiol produces a nitrosated cation that, in turn, reacts with a second nitrosothiol to produce nitrosated disulfide and the NO dimer. The nitrosated disulfide acts as a source of nitrosonium for nitrosothiol nitrosation, completing the catalytic cycle. The mechanism accounts for several unexplained facets of nitrosothiol chemistry in solution, including the observation that the decomposition of an RSNO is accelerated by O₂, mixtures of O₂ and NO, and other oxidants, that decomposition is inhibited by thiols and other antioxidants, that decomposition is dependent on sulfur substitution, and that decomposition often shows nonintegral kinetic orders.

The chemical mechanism by which nitrogenase enzymes catalyze the hydrogenation of N₂ (and other multiply bonded substrates) at the N^cFe₇MoS₉(homocitrate) active site (FeMo-co) is unknown, despite the accumulation of much data on enzyme reactivity and the influences of key amino acids surrounding FeMo-co. The mutual influences of H₂, substrates, and the inhibitor CO on reactivity are key experimental tests for postulated mechanisms. Fundamental to all aspects of mechanism is the accumulation of H atoms (from e^- + H⁺) on FeMo-co, and the generation and influences of coordinated H₂. Here, I argue that the first introduction of H is via a water chain terminating at water 679 (PDB structure 1M1N, Azotobacter vinelandii) to one of the μ₃-S atoms (S3B) of FeMo-co. Next, using validated density functional calculations of a full chemical representation of FeMo-co and its connected residues (α-275^Cys, α-442^His), I have characterized more than 80 possibilities for the coordination of up to three H atoms, and H₂, and H + H₂, on the S2A, Fe2, S2B, Fe6, S3B domain of FeMo-co, which is favored by recent targeted mutagenesis results. Included are calculated reaction profiles for movements of H atoms (between S and Fe, and between Fe and Fe), for the generation of Fe−H₂, for association and dissociation of Fe−H₂ at various reduction levels, and for H/H₂ exchange. This is new hydrogen chemistry on an unprecedented coordination frame, with some similarities to established hydrogen coordination chemistry, and with unexpected and unprecedented structures such as Fe(S)₃(H₂)₂(H) octahedral coordination. General principles for the hydrogen chemistry of FeMo-co include (1) the stereochemical mobility of H bound to μ₃-S, (2) the differentiated endo- and exo- positions at Fe for coordination of H and/or H₂, and (3) coordinative allosteric influences in which structural and dynamic aspects of coordination at one Fe atom are affected by coordination at another Fe atom, and by H on S atoms. Evidence of end-differentiation in FeMo-co is described, providing a rationale for the occurrence of Mo. The reactivity results are discussed in the context of the Thorneley−Lowe scheme for nitrogenase reactions, and especially the scheme for the HD reaction (2H⁺ + 2e^- + D₂ ⇒ 2HD), using a model containing an H-entry site and at least two coordinative sites on FeMo-co. I propose that S3B is the H-entry site, suggest details for the H⁺ shuttle to S3B and subsequent movement of H atoms around FeMo-co preparatory to the binding and hydrogenation of N₂ and other substrates, and suggest how H could be transferred to an alkyne substrate. I propose that S2B (normally hydrogen bonded to α-195^His) has a modulatory function and is not an H-entry site. Finally, the recent first experimental trapping of a hydrogenated intermediate with EPR and ENDOR characterization is discussed, leading to a consensual model for the intermediate.

Trp-cage, a synthetic 20 residue polypeptide, is proposed to be an ultrafast folding synthetic miniprotein which utilizes tertiary contacts to define its native conformation. We utilized UV resonance Raman spectroscopy (UVRS) with 204 and 229 nm excitation to follow its thermal melting. Our results indicate that Trp-cage melting is complex, and it is not a simple two-state process. Using 204 nm excitation we probe the peptide secondary structure and find the Trp-cage's α-helix shows a broad melting curve where on average four α-helical amide bonds melt upon a temperature increase from 4 to 70 °C. Using 229 nm excitation we probe the environment of the Trp side chain and find that its immediate environment becomes more compact as the temperature is increased from 4 to 20 °C; however, further temperature increases lead to exposure of the Trp to water. The χ² angle of the Trp side chain remains invariant throughout the entire temperature range. Previous kinetic results indicated a single-exponential decay in the 4−70 °C temperature range, suggesting that Trp-cage behaves as a two-state folder. However, this miniprotein does not show clear two-state behavior in our steady-state studies. Rather it shows a continuous distribution of steady-state spectral parameters. Only the α-helix melting curve even hints of a cooperative transition. Possibly, the previous kinetic results monitor only a small region of the Trp-cage which locally appears two-state. This would then argue for spatially decoupled folding even for this small peptide.

We describe here the highly fluorescent self-assembled spherical aggregates of an azobenzene molecule without a specific ionic component in organic solution under UV light illumination. The first stage of trans-to-cis photoisomerization by UV light at 365 nm was followed by a significant enhancement, up to about 1000 times, of the emission from an azobenzene molecule (CN2Azo) with a long alkyl chain, which is due to the spontaneous formation of spherical organic aggregates. Fluorescence emission was further enhanced in the dark, and the quantum yield increased to about 0.3. We also report the significant size and structural changes of the aggregates, from nanometer-scale micelle-like aggregates to micrometer-scale vesicular aggregates, obtained only from the variation in the concentration of an azobenzene derivative. The light-driven azobenzene aggregates show the size and structure dependences of emission wavelength from violet-blue to green-yellow.

Dendrimer-like poly(ethylene oxide)s (PEOs) were synthesized by an iterative divergent approach combining anionic polymerization of ethylene oxide from multi-hydroxylated precursors and branching reactions of PEO chain ends. Partial deprotonation of the hydroxyls (<30%) and use of dimethyl sulfoxide as solvent proved crucial for a “controlled/living” polymerization of ethylene oxide at room temperature. These sequences of reactions allowed us to prepare a dendrimer-like PEO up to the eighth generation with a molar mass of 900 000 g mol^-1 and 384 external hydroxyl functions. All samples from generation 1 to 8 were characterized by ¹H NMR spectroscopy, light scattering, and viscometry. The evolution of the intrinsic viscosity versus the generation number of these dendrimer-like PEO is similar to that of regular dendrimers.

Three quasi-dynamic pharmacophore models have been constructed for the complement inhibitor peptide compstatin, using first principles. Uniform sampling along 5-ns molecular dynamics trajectories provided dynamic conformers that are thought to represent the entire conformational space for nine training set molecules, compstatin, four active analogues, and four inactive analogues. The pharmacophore models were built using mixed physicochemical and structural properties of residues indispensable for structural stability and activity. Owing to the size and flexibility of compstatin, one-dimensional probability distributions of intrapharmacophore point distances, angles, and dihedral angles of different analogues spread over wide and overlapping ranges. More robust two-dimensional distance−angle probability distributions for two pharmacophore models discriminated individual analogues in terms of specific distance−angle pairs, but overall failed to identify the active and the inactive analogues as two distinct groups. Two-dimensional distance−dihedral angle probability distributions in a third pharmacophore model allowed discrimination of the groups of active and inactive analogues more effectively, with the highest-activity analogue having distinct behavior. The present study indicates that more stringent structural constraints should be used for a set of structurally similar but flexible peptides, as opposed to organic molecules, to convert dynamic conformers into pharmacophore models. Flexibility is a general aspect of the structure and function of peptides and should be taken into account in ligand-based pharmacophore design. However, the discrimination of activity using multidimensional probability surfaces depends on the peptide system, the selection of the training set, the molecular dynamics protocol, and the selection of the type and number of pharmacophore points.

A new compound with electride characteristics, Li@calix[4]pyrrole, is designed in theory. The Li atom in Li@calix[4]pyrrole is ionized to form a cation and an excess electron anion. Its structure with C_4v symmetry resembles a cup-like shape. It may be a stable organic electride at room temperature. The first hyperpolarizability of the cup-like electride molecule is first investigated by the DFT (B3LYP) method. The result shows that this electride molecule has a considerably large first hyperpolarizability with β₀ = 7326 au (63.3 × 10^-30 esu), while the β₀ value of the related calix[4]pyrrole system is only 390 au. Obviously, the Li atom doped in calix[4]pyrrole brings a dramatic change to the electronic structure, so that the first hyperpolarizability of Li@calix[4]pyrrole is almost 20 times larger than that of calix[4]pyrrole. We find that the excess electron from the Li atom plays an important role in the large first hyperpolarizability of Li@calix[4]pyrrole. The present investigation reveals a new idea and different means for designing and synthesizing high-performance NLO materials.

Iron(III)-doped TiO₂ nanopowders, with controlled iron to titanium atomic ratios (R_Fe/Ti) ranging from nominal 0 to 20%, were synthesized using oxidative pyrolysis of liquid-feed metallorganic precursors in a radiation-frequency (RF) thermal plasma. The valence of iron doped in the TiO₂, phase formation, defect structures, band gaps, and magnetic properties of the resultant nanopowders were systematically investigated using Mössbauer spectroscopy, XRD, Raman spectroscopy, TEM/HRTEM, UV−vis spectroscopy, and measurements of magnetic properties. The iron doped in TiO₂ was trivalent (3+) in a high-spin state as determined by the isomer shift and quadrupole splitting from the Mössbauer spectra. No other phases except anatase and rutile TiO₂ were identified in the resultant nanopowders. Interestingly, thermodynamically metastable anatase predominated in the undoped TiO₂ nanopowders, which can be explained from a kinetic point of view based on classical homogeneous nucleation theory. With iron doping, the formation of rutile was strongly promoted because rutile is more tolerant than anatase to the defects such as oxygen vacancies resulting from the substitution of Fe³⁺ for Ti⁴⁺ in TiO₂. The concentration of oxygen vacancies reached a maximum at R_Fe/Ti = 2% above which excessive oxygen vacancies tended to concentrate. As a result of this concentration, an extended defect like crystallographic shear (CS) structure was established. With iron doping, red shift of the absorption edges occurred in addition to the d−d electron transition of iron in the visible light region. The as-prepared iron-doped TiO₂ nanopowders were paramagnetic in nature at room temperature.

Neutron diffraction with isotopic substitution (NDIS) experiments and molecular dynamics (MD) simulations have been used to examine the pentose d-xylose in aqueous solution. By specifically labeling d-xylose molecules with a deuterium atom at the nonexchangeable hydrogen position on C4, it was possible to extract information about the atomic structuring around just that specific position. The MD simulations were found to give satisfactory agreement with the experimental NDIS results and could be used to help interpret the scattering data in terms of the solvent structuring as well as the intramolecular hydroxyl conformations. Although the experiment is challenging and on the limit of modern instrumentation, it is possible by careful analysis, in conjunction with MD studies, to show that the conformation trans to H4 at 180° is strongly disfavored, in excellent agreement with the MD results. This is the first attempt to use NDIS experiments to determine the rotameric conformation of a hydroxyl group.

The only molecules that are currently known to fold into unique three-dimensional conformations and perform sophisticated functions are biological polymers − proteins and some RNA molecules. Our aim is to create a nonbiological sequence-specific polymer that folds in aqueous solution. Toward that end, we synthesized sequence-specific 30mer, 45mer, and 60mer peptoid oligomers (N-substituted glycine polymers) consisting of 15mer units we chained together by disulfide and oxime linkages to mimic the helical bundle structures commonly found in proteins. Because these 15mer sequences were previously shown to form defined helical structures that aggregate together at submillimolar concentrations, we expected that by covalently linking multiple 15mers together, they might fold as helical bundles. To probe whether they folded, we used fluorescence resonance energy transfer (FRET) reporter groups. We found that certain constructs fold up with a hydrophobic core and have cooperative folding transitions. Such molecules may ultimately provide a platform for designing specific functions resembling those of proteins.

The first systematic study of diferrous dicyano dithiolates is described. Oxidation of [Fe₂(S₂C₂H₄)(CN)₂(CO)₄]^2- in the presence of cyanide and tertiary phosphines and of Fe₂(S₂C₂H₄)(CO)₄(PMe₃)₂ in the presence of cyanide affords a series of diferrous cyanide derivatives that bear a stoichiometric, structural, and electronic relationship to the H_ox^air state of the Fe-only hydrogenases. With PPh₃ as the trapping ligand, we obtained an unsymmetrical isomer of Fe₂(S₂C₂H₄)(μ-CO)(CN)₂(PPh₃)₂(CO)₂, as confirmed crystallographically. This diferrous cyanide features the semibridging CO-ligand, with Fe-μC bond lengths of 2.15 and 1.85 Å. Four isomers of Fe₂(S₂C₂H₄)(μ-CO)(CN)₂(PMe₃)₂(CO)₂ were observed, the initial product again being unsymmetrical but more stable isomers being symmetrical. DFT calculations confirm that the most stable isomers of Fe₂(S₂C₂H₄)(μ-CO)(CN)₂(PMe₃)₂(CO)₂ have cyanide trans to μ-CO. Oxidative decarbonylation also afforded the new tetracyanide [Fe₂(S₂C₂H₄)(μ-CO)(CN)₄(CO)₂]^2-. Insights into the oxidative decarbonylation mechanism of these syntheses come from the spectroscopic characterization of the tetracarbonyl [Fe₂(S₂C₂H₄)(μ-CO)(CN)₃(CO)₃]^-. This species reacts with PEt₃ to produce the stable adduct [Fe₂(S₂C₂H₄)(μ-CO)(CN)₃(CO)₂(PEt₃)]^-.

In this paper the role of the solvent in the formation of the charge-separated excited state of 9,9‘-bianthryl (BA) is examined by means of mixed molecular mechanical/quantum mechanical (QM/MM) calculations. It is shown that in weakly polar solvents a relaxed excited state is formed with an interunit angle that is significantly smaller than 90°. This relaxed excited state has a considerable dipole moment even in weakly polar solvents; for benzene and dioxane dipole moments of ca. 6 D were calculated, which is close to experimental data. These dipoles are induced by the solvent in the highly polarizable relaxed excited state of BA, and the dipole relaxation time is governed by solvent reorganizations. In polar solvent the charge separation is driven to completion by the stronger dipoles in the solvent and a fully charged separated excited state is formed with an interunit angle of 90°.

Recently, alkylene-linked heterodimers of tacrine (1) and 5-amino-5,6,7,8-tetrahydroquinolinone (2, hupyridone) were shown to exhibit higher acetylcholinesterase (AChE) inhibition than either monomeric 1 or 2. Such inhibitors are potential drug candidates for ameliorating the cognitive decrements in early Alzheimer patients. In an attempt to understand the inhibition mechanism of one such dimer, (RS)-(±)-N-9-(1,2,3,4-tetrahydroacridinyl)-N‘-5-[5,6,7,8-tetrahydro-2‘(1‘H)-quinolinonyl]-1,10-diaminodecane [(RS)-(±)-3] bisoxalate, the racemate was soaked in trigonal Torpedo californica AChE (TcAChE) crystals, and the X-ray structure of the resulting complex was solved to 2.30 Å resolution. Its structure revealed the 1 unit bound to the “anionic” subsite of the active site, near the bottom of the active-site gorge, as seen for the 1/TcAChE complex. Interestingly, only the (R)-enantiomer of the 2 unit was seen in the peripheral “anionic” site (PAS) at the top of the gorge, and was hydrogen-bonded to the side chains of residues belonging to an adjacent, symmetry-related AChE molecule covering the gorge entrance. When the same racemate was soaked in orthorhombic crystals of TcAChE, in which the entrance to the gorge is more exposed, the crystal structure of the corresponding complex revealed no substantial enantiomeric selectivity. This observation suggests that the apparent enantiomeric selectivity of trigonal crystals of TcAChE for (R)-3 is mainly due to crystal packing, resulting in preferential binding of one enantiomeric inhibitor both to its “host” enzyme and to its neighbor in the asymmetric unit, rather than to steric constraints imposed by the geometry of the active-site gorge.

High throughput screening (HTS) of a 205 member Schiff base salicylaldimine ligand library derived from salicylaldehydes bearing bulky ortho-substituents, i.e., 9-anthracenyl, 1,4,5,8-tetramethylanthracenyl or triptycenyl, reacted in-situ with (p-tolyl)CrCl₂(thf)₃, identified two new classes of highly active chromium based systems for the oligomerization and polymerization of ethylene, respectively. The polymerization system comprises bidentate ortho-substituted anthracenyl Schiff bases bearing small primary or secondary alkyl imine substituents. The oligomerization catalysts are based upon tridentate ortho-triptycenyl-substituted Schiff bases with pyridylmethyl or quinolyl substituents. Validation tests confirmed polymerization productivities of up to 3000 g·mmol^-1h^-1bar^-1 for the polymerization catalyst systems while the oligomerization catalysts gave productivities up to 10 000 g·mmol^-1h^-1bar^-1. Key catalyst precursors have been characterized by X-ray crystallography.

A simple method for the construction of a stable, tunable, self-assembled command layer for liquid crystal display purposes is described. A pyridine-functionalized oligosiloxane spontaneously forms an anisotropic, grooved surface on indium−tin-oxide, enabling it to align liquid crystalline molecules. The pyridine functions act as seeds for the epitaxial growth of stacks of highly ordered zinc phthalocyanines, the height of which can be controlled. These stacks increase the interaction between the surface and the liquid crystalline matrix by amplifying the surface ordering into the liquid crystal bulk. By varying the height of the stacks, direct control over the properties of the liquid crystal domains is achieved. These properties can be further tuned by adding to the liquid crystal, micro- and nanomolar concentrations of nitrogen-containing compounds, which are capable of interacting with and dissolving the stacks. The procedures we describe offer possibilities to use such tunable systems in LCD-based sensor devices as well as in solar-cell applications.

To study the initial chemical events related to the detonation of triacetonetriperoxide (TATP), we have performed a series of molecular dynamics (MD) simulations. In these simulations we used the ReaxFF reactive force field, which we have extended to reproduce the quantum mechanics (QM)-derived relative energies of the reactants, products, intermediates, and transition states related to the TATP unimolecular decomposition. We find excellent agreement between the QM-predicted reaction products and those observed from 100 independent ReaxFF unimolecular MD cookoff simulations. Furthermore, the primary reaction products and average initiation temperature observed in these 100 independent unimolecular cookoff simulations match closely with those observed from a TATP condensed-phase cookoff simulation, indicating that unimolecular decomposition dominates the thermal initiation of the TATP condensed phase. Our simulations demonstrate that thermal initiation of condensed-phase TATP is entropy-driven (rather than enthalpy-driven), since the initial reaction (which mainly leads to the formation of acetone, O₂, and several unstable C₃H₆O₂ isomers) is almost energy-neutral. The O₂ generated in the initiation steps is subsequently utilized in exothermic secondary reactions, leading finally to formation of water and a wide range of small hydrocarbons, acids, aldehydes, ketones, ethers, and alcohols.

Four isomorphous complexes of formula [M(L)₄(H₂O)₂]SO₄·2H₂O (M = Co, 1a; Ni, 1b; Cu, 1c; Zn, 1d) have been isolated and characterized by single-crystal X-ray diffraction and neutron diffraction using the quasi-Laue diffractometer VIVALDI at the Institut Laue-Langevin as well as by thermogravimetric analysis. The structures contain a discrete, strongly hydrogen-bonded water tetramer which causes a significant distortion of the metal coordination sphere in each case. Partial atomic charges and hardness analysis (PACHA) calculations reveal that the shortest hydrogen bonds are not the strongest in this constrained, cyclic solid-state structure and show that the distortion at the metal center is caused by the drive to maintain the integrity of the water tetramer. The system undergoes a disorder−order transition on slow cooling that provides insight into the nature of communication between water squares.

The iroA locus encodes five genes (iroB, iroC, iroD, iroE, iroN) that are found in pathogenic Salmonella and Escherichia coli strains. We recently reported that IroB is an enterobactin (Ent) C-glucosyltransferase, converting the siderophore into mono-, di-, and triglucosyl enterobactins (MGE, DGE, and TGE, respectively). Here, we report the characterization of IroD and IroE as esterases for the apo and Fe³⁺-bound forms of Ent, MGE, DGE, and TGE, and we compare their activities with those of Fes, the previously characterized enterobactin esterase. IroD hydrolyzes both apo and Fe³⁺-bound siderophores distributively to generate DHB−Ser and/or Glc−DHB−Ser, with higher catalytic efficiencies (k_cat/K_m) on Fe³⁺-bound forms, suggesting that IroD is the ferric MGE/DGE esterase responsible for cytoplasmic iron release. Similarly, Fes hydrolyzes ferric Ent more efficiently than apo Ent, confirming Fes is the ferric Ent esterase responsible for Fe³⁺ release from ferric Ent. Although each enzyme exhibits lower k_cat's processing ferric siderophores, dramatic decreases in K_m's for ferric siderophores result in increased catalytic efficiencies. The inability of Fes to efficiently hydrolyze ferric MGE, ferric DGE, or ferric TGE explains the requirement for IroD in the iroA cluster. IroE, in contrast, prefers apo siderophores as substrates and tends to hydrolyze the trilactone just once to produce linearized trimers. These data and the periplasmic location of IroE suggest that it hydrolyzes apo enterobactins while they are being exported. IroD hydrolyzes apo MGE (and DGE) regioselectively to give a single linear trimer product and a single linear dimer product as determined by NMR.

Two chiral bent-core mesogens Pn−O−PIMB(n − 2)* (n = 9 and 10) and their oxygen analogues Pn−O−PIMB(n − 2)*−(n − 4)O (n = 8, 9, and 10) with ω-[(S)-amyloxy]alkoxy terminal groups were prepared, and their phase structures were investigated by means of electro-optic, polarization reversal current and second harmonic generation measurements in order to clarify the effect of the interlayer steric interaction on the emergence of polar orderings. The odd−even behavior for the alternative appearance of ferroelectricity and antiferroelectricity was observed in two homologous series; the bent-core mesogens P10−O−PIMB8*, P8−O−PIMB6*−4O, and P10−O−PIMB8*−6O in addition to the previously reported P6−O−PIMB4* and P8−O−PIMB6*, where the length of chains n is even, exhibited ferroelectric phases. On the contrary, the mesogens P7−O−PIMB5*, P9−O−PIMB7*, and P9−O−PIMB7*−5O, where n is odd, showed antiferroelectric phases. It is obvious that the interlayer steric interaction plays a major role for the emergence of a variety of phase structures.

Synthesis of an analogue of the C-cluster of C. hydrogenoformans carbon monoxide dehydrogenase requires formation of a planar Ni^II site and attachment of an exo iron atom in the core unit NiFe₄S₅. The first objective has been achieved by two reactions:  (i) displacement of Ph₃P or Bu^tNC at tetrahedral Ni^II sites of cubane-type [NiFe₃S₄]⁺ clusters with chelating diphosphines, and (ii) metal atom incorporation into a cuboidal [Fe₃S₄]⁰ cluster with a M⁰ reactant in the presence of bis(1,2-dimethylphosphino)ethane (dmpe). The isolated product clusters [(dmpe)MFe₃S₄(LS₃)]^2- (M = Ni^II (9), Pd^II (12), Pt^II (13); LS₃ = 1,3,5-tris((4,6-dimethyl-3-mercaptophenyl)thio)-2,4,6-tris(p-tolylthio)benzene(3−)) contain the cores [MFe₃(μ₂-S*)(μ₃-S)₃]⁺ having planar M^IIP₂S₂ sites and variable nonbonding M···S* distances of 2.6−3.4 Å. Reaction (i) involves a tetrahedral → planar Ni^II structural change between isomeric cubane and cubanoid [NiFe₃S₄]⁺ cores. Based on the magnetic properties of 12 and earlier considerations, the S = ⁵/₂ ground state of the cubanoid cluster arises from the [Fe₃S₄]^- fragment, whereas the S = ³/₂ ground state of the cubane cluster is a consequence of antiferromagnetic coupling between the spins of Ni²⁺ (S = 1) and [Fe₃S₄]^-. Other substitution reactions of [NiFe₃S₄]⁺ clusters and 1:3 site-differentiated [Fe₄S₄]²⁺ clusters are described, as are the structures of 12, 13, [(Me₃P)NiFe₃S₄(LS₃)]^2-, and [Fe₄S₄(LS₃)L‘]^2- (L‘ = Me₂NC₂H₄S^-, Ph₂P(O)C₂H₄S^-). This work significantly expands our initial report of cluster 9 (Panda et al. J. Am. Chem. Soc. 2004, 126, 6448−6459) and further demonstrates that a planar M^II site can be stabilized within a cubanoid [NiFe₃S₄]⁺ core.

The mechanism of the cross-coupling of phenylboronic acid with acetic anhydride, a viable model of the widely used Suzuki reaction, has been studied by DFT calculations at the BP86/6-31G* level of theory. Two alternative catalytic cycles have been investigated, one starting from a neutral Pd(0)L₂ complex, the other from an anionic “Jutand-type” [Pd(0)L₂X]^- species. The reaction profiles are in good agreement with the experimental findings, as both pathways require only moderate activation energies. Both pathways are dominated by cis-configured square-planar palladium(II)diphosphine intermediates. Despite careful investigations, we did not find in this model reaction any evidence for five-coordinate palladium(II) intermediates, which are commonly believed to cause the profound effects of counterions in palladium-catalyzed transformations. Instead, our calculations suggest that the higher catalytic activity of anionic complexes, such as [Pd(PMe₃)₂OAc]^-, may arise from their stronger ability to coordinate to carbon electrophiles. The transmetalation sequence is the same for both catalytic cycles, involving the dissociation of one phosphine ligand from the palladium. In the decisive transition state, in which the phenyl group is transferred from boron to palladium, the acetate base is found to be in a bridging coordination between these two atoms.

It was recently shown experimentally that 5-(guanidiniocarbonyl)-1H-pyrrole-2-carboxylate 1, a self-complementary zwitterion, dimerizes even in water with an unprecedented high association constant of K = 170 M^-1 (J. Am. Chem. Soc. 2003, 125, 452−459). To get an insight into the importance of the various noncovalent binding interactions and of their interplay (electrostatic interactions, hydrogen binding, cooperative effects), we employ density functional theory to study the stability of several “knock-out” analogues in which single hydrogen bonds within these multiple point binding motif are switched off by replacing N−H hydrogen-donor groups with either methylene groups or an oxygen ether bridge. The influence of a highly polar solvent on the dimer stabilities is also examined. These calculations reproduce the experimental data for zwitterion 1. A comparison of 1 with the arginine dimer shows that the energy contents of the monomers also significantly influence the dimer stabilities. The analysis of the various “knock-out” analogues reveals as a main conclusion that simple models either based just on hydrogen-bond counting or on the assumption that the charge interaction by itself is the main and dominant factor fail to explain the stability of such self-assembled dimers. Our computations show that the hydrogen-bond network, the electrostatic attraction, and also their mutual interactions are responsible for the high stability of zwitterion 1.

To explore the relationship between the assembly of the 30S ribosomal subunit and interactions among the constituent components, 16S RNA and proteins, relative binding free energies of the T. thermophilus 30S proteins to the 16S RNA were studied based on an implicit solvent model of electrostatic, nonpolar, and entropic contributions. The late binding proteins in our assembly map were found not to bind to the naked 16S RNA. The 5‘ domain early kinetic class proteins, on average, carry the highest positive charge, get buried the most upon binding to 16S RNA, and show the most favorable binding. Some proteins (S10/S14, S6/S18, S13/S19) have more stabilizing interactions while binding as dimers. Our computed assembly map resembles that of E. coli; however, the central domain path is more similar to that of A. aeolicus, a hyperthermophilic bacteria.

Hydrogen-bonded disk-shaped aggregates (rosettes) composed of azobenzene-appended melamine and barbiturate or cyanurate are investigated in view of their hierarchical organization and photoresponsive behavior by ¹H NMR and UV/vis spectroscopies, dynamic light scattering, and gelation behavior in aliphatic solvents and liquid crystalline behavior in bulk state. In the bulk state the rosette possessing a sterically bulky tridodecyloxyphenyl substituent in the barbiturate component stacks in an offset arrangement to form a rectangular columnar mesophase, whereas in aliphatic solvents it does not hierarchically organize into higher-order columnar aggregates. This drawback is improved by exchanging the barbiturate component into a more sterically nondemanding N-dodecylcyanurate component. The resulting new rosette stacks in a face-to-face arrangement to form a hexagonal columnar mesophase in the bulk state and hierarchically organizes into elongated fibrous aggregates in cyclohexane, which eventually leads to the formation of organogel. Dynamic light scattering and UV−vis experiments upon UV-irradiation of the columnar aggregates in cyclohexane revealed that the dissociation and the reformation of columnar aggregates can be controlled by the trans−cis isomerization of the azobenzene moiety. Molecular modeling indicates that the rosette possessing cis-azobenzene side chains loses its planarity. Using this photoinduced morphological change of the rosette, photoresponsive organogel is created by the use of a disk-shaped supramolecule the first time.

In this report, we describe a general methodology to determine the extent of alloying or atomic distribution quantitatively in bimetallic nanoparticles (NPs) by X-ray absorption spectroscopy (XAS). The structural parameters determined in these studies serve as a quantitative index and provide a general route to determine the structural aspects of the bimetallic NPs. We have derived various types of possible structural models based on the extent of alloying and coordination number parameters of bimetallic NPs. We also discussed the nature of homo- and heterometallic interactions in bimetallic NPs based on the extent of alloying. Herein, we use carbon-supported platinum−ruthenium bimetallic nanoparticles to demonstrate the proposed methodology, and this can be extended further to get more insights into the alloying extent or atomic distribution of other bimetallic systems. The results demonstrated in this paper open up methods to determine the atomic distribution of bimetallic NPs, which is an extremely important parameter that strongly influences the physicochemical properties of NPs and their applications.

(η⁶-Naphthalene)Mn(CO)₃⁺ is reduced reversibly by two electrons in CH₂Cl₂ to afford (η⁴-naphthalene)Mn(CO)₃^-. The chemical and electrochemical reductions of this and analogous complexes containing polycyclic aromatic hydrocarbons (PAH) coordinated to Mn(CO)₃⁺ indicate that the second electron addition is thermodynamically easier but kinetically slower than the first addition. Density functional theory calculations suggest that most of the bending or folding of the naphthalene ring that accompanies the η⁶ → η⁴ hapticity change occurs when the second electron is added. As an alternative to further reduction, the 19-electron radicals (η⁶-PAH)Mn(CO)₃ can undergo catalytic CO substitution when phosphite nucleophiles are present. Chemical reduction of (η⁶-naphthalene)Mn(CO)₃⁺ and analogues with one equivalent of cobaltocene affords a syn-facial bimetallic complex (η⁴,η⁶-naphthalene)Mn₂(CO)₅, which contains a Mn−Mn bond. Catalytic oxidative activation under CO reversibly converts this complex to the zwitterionic syn-facial bimetallic (η⁴,η⁶-naphthalene)Mn₂(CO)₆, in which the Mn−Mn bond is cleaved and the naphthalene ring is bent by 45°. Controlled reduction experiments at variable temperatures indicate that the bimetallic (η⁴,η⁶-naphthalene)Mn₂(CO)₅ originates from the reaction of (η⁴-naphthalene)Mn(CO)₃^- acting as a nucleophile to displace the arene from (η⁶-naphthalene)Mn(CO)₃⁺. Heteronuclear syn-facial and anti-facial bimetallics are formed by the reduction of mixtures of (η⁶-naphthalene)Mn(CO)₃⁺ and other complexes containing a fused polycyclic ring, e.g., (η⁵-indenyl)Fe(CO)₃⁺ and (η⁶-naphthalene)FeCp⁺. The great ease with which naphthalene-type manganese tricarbonyl complexes undergo an η⁶ → η⁴ hapticity change is the basis for the formation of both the homo- and heteronuclear bimetallics, for the observed two-electron reduction, and for the far greater reactivity of (η⁶-PAH)Mn(CO)₃⁺ complexes in comparison to monocyclic arene analogues.

The first phase of the total synthesis of thiostrepton (1), a highly complex thiopeptide antibiotic, is described. After a brief introduction to the target molecule and its structural motifs, it is shown that retrosynthetic analysis of thiostrepton reveals compounds 23, 24, 26, 28, and 29 as potential key building blocks for the projected total synthesis. Concise and stereoselective constructions of all these intermediates are then described. The synthesis of the dehydropiperidine core 28 was based on a biosynthetically inspired aza-Diels−Alder dimerization of an appropriate azadiene system, an approach that was initially plagued with several problems which were, however, resolved satisfactorily by systematic investigations. The quinaldic acid fragment 24 and the thiazoline−thiazole segment 26 were synthesized by a series of reactions that included asymmetric and other stereoselective processes. The dehydroalanine tail precursor 23 and the alanine equivalent 29 were also prepared from the appropriate amino acids. Finally, a method was developed for the direct coupling of the labile dehydropiperidine key building block 28 to the more advanced and stable peptide intermediate 27 through capture with the highly reactive alanine equivalent 67 under conditions that avoided the initially encountered destructive ring contraction process.

The completion of the total synthesis of thiostrepton (1) is described. The synthesis proceeded from key building blocks 2−5, which were assembled into a growing substrate that finally led to the target molecule. Thus, the dehydropiperidine peptide core 2 was, after appropriate manipulation, coupled to the thiazoline−thiazole fragment 3, and the resulting product was advanced to intermediate 11 possessing the thiazoline−thiazole macrocycle. The bis-dehydroalanine tail equivalent 4 and the quinaldic acid fragment 5 were then sequentially incorporated, and the products so obtained were further elaborated to forge the second macrocycle of the molecule. Several roadblocks encountered along the way were systematically investigated and overcome, finally opening the way, through intermediates 20, 32, 44, 45, and 46, to the targeted natural product, 1.

The elongated dihydrogen complex (1) reacts with 1,1-diphenyl-2-propyn-1-ol and 2-methyl-3-butyn-2-ol to give the hydride-hydroxyvinylidene-π-alkynol derivatives [OsH{CCHC(OH)R₂}{η²-HC⋮CC(OH)R₂}(PⁱPr₃)₂]BF₄ (R = Ph (2), Me (3)), where the π-alkynols act as four-electron donor ligands. Treatment of 2 and 3 with HBF₄ and coordinating solvents leads to the dicationic hydride-alkenylcarbyne compounds [OsH(⋮CCHCR₂)S₂(PⁱPr₃)₂][BF₄]₂ (R = Ph, S = H₂O (4), CH₃CN (5); R = Me, S = CH₃CN (6)), which in acetonitrile evolve into the alkenylcarbene complexes [Os(CHCHCR₂)(CH₃CN)₃(PⁱPr₃)₂][BF₄]₂ (R = Ph (7), Me (8)) by means of a concerted 1,2-hydrogen shift from the osmium to the carbyne carbon atom. Treatment of 2-propanol solutions of 5 with NaCl affords OsHCl₂(⋮CCHCPh₂)(PⁱPr₃)₂ (10), which reacts with AgBF₄ and acetonitrile to give [OsHCl(⋮CCHCPh₂)(CH₃CN)(PⁱPr₃)₂]BF₄ (11). In this solvent complex 11 is converted to [OsCl(CHCHCPh₂)(CH₃CN)₂(PⁱPr₃)₂]BF₄ (12). Complex 5 reacts with CO to give [Os(CHCHCPh₂)(CO)(CH₃CN)₂(PⁱPr₃)₂][BF₄]₂ (15). DFT calculations and kinetic studies for the hydride-alkenylcarbyne to alkenylcarbene transformation show that the difference of energy between the starting compounds and the transition states, which can be described as η²-carbene species increases with the basicity of the metallic center. The X-ray structures of 4 and 7 and the rotational barriers for the carbene ligands of 7, 8, and 12 are also reported.