Search

Author(s): Zh. E. Starkova [sup.1] , N. Yu. Polovkov [sup.1] , A. Yu. Kanateva [sup.1] , R. S. Borisov [sup.1] [sup.2] , V. G. Zaikin [sup.1] Author Affiliations: (1) grid.423490.8, [...], Preliminary transformation into sulfonium salts by an electrophilic reaction with alkyl formates in the presence of trifluoromethanesulfonic acid is proposed for the study and analysis of non-polar organic sulfides by matrix-assisted laser desorption/ionization (MALDI). The test samples are thiabicyclanes with different positions of the sulfur atom and methyl substituents (2- and 3-thiabicyclo[4.4.0] decanes, 7- and 8-thiabicyclo [4.3.0] nonanes). The reaction used provide quantitative S-alkylation under mild conditions. In MALDI mass spectra of sulfonium salts, only peaks of corresponding sulfonium cations were observed, the masses of which corresponded to the sum of molecular weights of the sulfide and the increment of the introduced alkyl group. Drastic qualitative and quantitative differences were found and interpreted in the mass spectra recorded in the collision-induced dissociation mode for regio-isomeric sulfonium cations.

Author(s): Poulikos I. Poulikakos [sup.1] , Yogindra Persaud [sup.2] , Manickam Janakiraman [sup.2] , Xiangju Kong [sup.3] , Charles Ng [sup.4] , Gatien Moriceau [sup.3] , Hubing Shi [sup.3] , [...], Although clinical trials have shown that RAF inhibitors prolong the survival of patients with BRAF-mutant melanoma, resistance inevitably develops; resistance is shown here to be frequently mediated by the expression of splicing variants of mutant BRAF. Mechanism of RAF inhibitor resistance Although recent clinical trials have shown the efficacy of B-RAF inhibitors in the treatment of melanomas with activating B-RAF mutations, the patients inevitably develop resistance. David Solit and colleagues now identify a mechanism of acquired resistance conferred by a structural change in B-RAF itself. The expression of a 61-kilodalton splice variant of mutant B-RAF leads to enhanced B-RAF dimerization, rendering it resistant to kinase inhibitors. This variant was found to be expressed in 6 of 19 patients who had developed resistance to the B-RAF inhibitor PLX4032. Activated RAS promotes dimerization of members of the RAF kinase family.sup.1,2,3. ATP-competitive RAF inhibitors activate ERK signalling.sup.4,5,6,7 by transactivating RAF dimers.sup.4. In melanomas with mutant BRAF(V600E), levels of RAS activation are low and these drugs bind to BRAF(V600E) monomers and inhibit their activity. This tumour-specific inhibition of ERK signalling results in a broad therapeutic index and RAF inhibitors have remarkable clinical activity in patients with melanomas that harbour mutant BRAF(V600E).sup.8. However, resistance invariably develops. Here, we identify a new resistance mechanism. We find that a subset of cells resistant to vemurafenib (PLX4032, RG7204) express a 61-kDa variant form of BRAF(V600E), p61BRAF(V600E), which lacks exons 4-8, a region that encompasses the RAS-binding domain. p61BRAF(V600E) shows enhanced dimerization in cells with low levels of RAS activation, as compared to full-length BRAF(V600E). In cells in which p61BRAF(V600E) is expressed endogenously or ectopically, ERK signalling is resistant to the RAF inhibitor. Moreover, a mutation that abolishes the dimerization of p61BRAF(V600E) restores its sensitivity to vemurafenib. Finally, we identified BRAF(V600E) splicing variants lacking the RAS-binding domain in the tumours of six of nineteen patients with acquired resistance to vemurafenib. These data support the model that inhibition of ERK signalling by RAF inhibitors is dependent on levels of RAS-GTP too low to support RAF dimerization and identify a novel mechanism of acquired resistance in patients: expression of splicing isoforms of BRAF(V600E) that dimerize in a RAS-independent manner.

The N-H bond dissociation energy in benzamide in the gas phase is calculated to explain the thermochemical properties of benzoylnitrene radical anion.

The ab initio and Rice-Ramsperger-Kassel-Marcus (RRKM) techniques are employed to study the photodissociation of 1,3,5-triazine at different wavelengths of the absorbed photon. The analysis proves the inconsistency in the translational energy distributions of the HCN moieties.

The semiclassical surface-hopping and quantum model simulations for [F.sub.2] and ClF in solid Ar are employed to explain the dynamics of electronic states and spin-flip for photodissociation of dihalogens in matrices.

The basic principles underlying the remote electronic effects of [Mg.sup.2} on the strength of a simple model of the P-O bond are explored. The results have shown that an individual bond might be strengthened by complex formation but the dissociation is globally more favorable due to other more dominant driving forces.

The enthalpies of synthesized multicomponent gas hydrates and the influence of guest molecules such as [C.sub.2][H.sub.6], [C.sub.3][H.sub.8], and C[O.sub.2] on their thermal behavior were determined. It was seen that when the difference in guest-to-cavity size ratio between the replaced methane and the replacing guest molecule is significant.

The hole-burning (HB) spectra of phenol-[Ar.sub.n] (Ph-OH-[Ar.sub.n]) clusters with n=1, 2 were measured in molecular beam to clarify the possible existence of isomers. It was seen that two species originated from n=1 cluster and one of the species was found to originate from dissociation of n=2 cluster and presence only one isomer in the molecular beam for both n=1 and n=2 clusters was confirmed.

The vibrationally mediated photodissociation dynamics of [C.sub.2][H.sub.4.sup.} excited through the [B.sup.2][A.sub.g] state are described. Analysis of the multimass images yielded both the translational energy distributions for the two dissociation channels and the branching between them as a function of excitation energy and the dissociation of ions consistently gave enhanced branching to the H elimination channel.

A prototypical case of molecular radical cation is described, whose electrostatic charge distribution is obtained by its conformational structures. The cationic charge is shown to be localized in a single site or two different sites depending on the molecular conformation.

The Si[O.sub.2] dissociation was studied by electron microscopy and Rutherford backscattering spectrometry. Large holes in non-implanted oxide layers were seen which may occur due to defects located at the Si/Si[O.sub.2] interface and an inhomogeneous dissociation of as-grown and implanted thin thermally grown Si[O.sub.2] films was observed during annealing at high temperature in ultra-pure neutral ambient at normal pressure.

The dissociative adsorption of [N.sub.2] is studied at both monatomic steps and flat regions on the surfaces of the 4d transition metals from Zr to Pd. It is found that when going from terrace to step active site, the early transition metals, the geometric and electronic effects work in opposition, while in case of 4d metals these effects work in combination, producing a more marked reduction in activation energy.

Cohesin's hinges are not just dimerization domains, as they are essential for cohesin's association with chromosomes, which is blocked by artificially holding hinge domains together but not by preventing Scc1's dissociation from SMC ATPase heads. The results have indicated that entry of DNA into cohesin's ring requires transient dissociation of Smc1 and Smc3 hinge domains.

We compare electron capture dissociation (ECD) of doubly protonated and divalent metal-adducted tyrosine O-sulfated peptides without basic amino acid residues. ECD of doubly protonated Tyr2-sulfated cholecystokinin (CCKS) and doubly protonated Tyrl2-sulfated gastrin II (GST) resulted in complete loss of S[O.sub.3] from all product ions. Thus, contrary to typical ECD behavior, localization of the sulfate groups was not possible. By contrast, ECD of Ca-, Mn-, Zn-, and Fe-adducted CCKS and ECD of deprotonated GST with two calcium adducts, i.e., [[GST + 2Ca - H].sup.3+], resulted in sulfated c'- and [z.sup.*]-type product ions with high sequence coverage, thereby allowing both sequencing and sulfate localization. In addition, divalent metal adduction provided improved positive mode ionization efficiency for these peptides. The drastically different fragmentation behavior observed in ECD of protonated and metal-adducted CCKS and GST, respectively, is proposed to be a consequence of the absence of basic amino acid residues, promoting a mobile proton-like fragmentation mechanism, including abundant sulfate loss, for protonated species. Retention of sulfate groups was also observed in electron detachment dissociation (EDD) of CCKS and GST. However, the EDD fragmentation efficiency was much lower than that of ECD and very limited fragmentation was observed in EDD of GST, precluding localization of the sulfate group in that peptide.

Product state distributions of the CO produced in the 308-nm photolysis of acetaldehyde show clear evidence of two dissociation mechanisms. One is attributed to the conventional transition state mechanism predicted by theory, with high rotational and translational energy of the CO and a pronounced v [perpendicular to] J vector correlation. However, as much as 15 % of the reaction flux proceeds via another pathway that produces low CO rotational and translational energy, very high C[H.sub.4] internal energy, and no correlation between the CO velocity and angular momentum vectors. The attributes of this channel are dynamically similar to the recently reported 'roaming atom' mechanism in formaldehyde. We therefore speculate that the second pathway in acetaldehyde also occurs via a roaming mechanism in the C[H.sub.3] + HCO exit channel that decays into the C[H.sub.4] + CO channel. photochemistry | photodissociation dynamics | product state distributions | roaming atom | transition state

Electron capture dissociation (ECD) of proteins in Fourier transform ion cyclotron resonance mass spectrometry usually leads to charge reduction and backbone-bond cleavage, thereby mostly retaining labile, intramolecular noncovalent interactions. In this report, we evaluate ECD of the 84-kDa noncovalent heptameric gp31 complex and compare this with sustained off-resonance irradiation collisionally activated dissociation (SORI-CAD) of the same protein. Unexpectedly, the 21+ charge state of the gp31 oligomer exhibits a main ECD pathway resulting in a hexamer and monomer, disrupting labile, intermolecular noncovalent bonds and leaving the backbone intact. Unexpectedly, the charge separation over the two products is highly proportional to molecular weight. This indicates that a major charge redistribution over the subunits of the complex does not take place during ECD, in contrast to the behavior observed when using SORI-CAD. We speculate that the ejected monomer retains more of its original structure in ECD, when compared to SORI-CAD. ECD of lower charge states of gp31 does not lead to dissociation of noncovalent bonds. We hypothesize that the initial gas-phase structure of the 21+ charge state is significantly different from the lower charge states. These structural differences result in the different reaction pathways when using ECD.

The first quantum chemical effort dealing with the mechanism of action of anticancer titanocene derivatives is described. The results support the view that titanocene might dissociate prior to binding to DNA, and most likely the active agent responsible for the anticancer activity is [[Ti(H2O).sub.6].sup.4+].

A series of crown ethers, 12-crown-4, 15-crown-5, 18-crown-6, and dibenzo-30-crown-10, are examined as a possible means of shifting the mobilities of peptide ions. In this approach, a crown ether is added to a solution containing a mixture of peptides and is electrosprayed into the gas phase in order to create distributions of peptide--crown complexes. The ion complexes have different mobilities than the naked peptide ions, and the crown ether molecules appear to interact specifically with basic sites in the peptides thus providing some sequence selectivity. After the peptide-crown complexes are separated by ion mobility spectrometry, the ions can be collisionally activated to dissociate the complex (forming the naked peptide ions) prior to m/z analysis. The overall effect is that complex formation shifts peptide ions to different regions of the mobility spectrum, extending the ability to resolve components. The approach is illustrated by examining isobaric dipeptides as well as a combinatorial library containing 27 tripeptides. Cross sections for the series of crown ether ions and complexes that are observed are reported.

Infrared multiphoton dissociation (IRMPD) of N-terminal sulfonated peptides improves de novo sequencing capabilities in a quadrupole ion trap mass spectrometer. Not only does IRMPD promote highly efficient dissociation of the N-terminal sulfonated peptides but also the entire series of y ions down to the [y.sub.1] fragment may be detected due to alleviation of the low-mass cutoff problem associated with conventional collisional activated dissociation (CAD) methods in a quadrupole ion trap. Commercial de novo sequencing software was applied for the interpretation of CAD and IRMPD MS/MS spectra collected for seven unmodified peptides and the corresponding N-terminal sulfonated species. In most cases, the additional information obtained by N-terminal sulfonation in combination with IRMPD provided significant improvements in sequence identification. The software sequence tag results were combined with a commercial database searching algorithm to interpret sequence information of a tryptic digest on [alpha]-casein s1. Energy-variable CAD studies confirmed a 30-40% reduction in the critical energies of the N-terminal sulfonated peptides relative to unmodified peptides. This reduction in dissociation energy facilitates IRMPD in a quadrupole ion trap.

Free radicals, electrophiles, and endogenous reactive intermediates are generated during normal physiological processes and are capable of modifying DNA, lipids, and proteins. However, elevated levels of oxidative modifications of proteins by reactive species are implicated in the etiology and pathology of oxidative stress-mediated diseases, neurodegeneration, and aging. A mass spectrometry-based approach is reported that aids to the identification and characterization of carbonyl-modified proteins. The method uses N'-aminooxymethylcarbonylhydrazino D-biotin, a biotinylated hydroxylamine derivative that forms an oxime derivative with the aldehyde/keto group found in oxidatively modified proteins. In this paper, the method is demonstrated for one class of carbonyl-modified proteins, namely, oxylipid peptide and protein conjugates formed by Michael addition-type conjugation reactions of [alpha],[beta]-unsaturated aldehydic lipid peroxidation products with nucleophilic peptide side chains. This new application of an 'old' probe, which has been used for the detection of abasic sites in DNA strands, introduces a biotin moiety into the oxylipid peptide conjugate. The biotin-modified oxylipid peptide conjugate is then amenable to enrichment using avidin affinity capture. The described method represents an attractive alternative to hydrazine-based derivatization methods for oxidized peptides and proteins because the reduction step necessary for the transformation of the hydrazone bond to the chemically more stable hydrazine bond can be omitted. Tandem mass spectrometry of the labeled oxylipid peptide conjugates indicates that the biotin moiety is at least partially retained on the fragment ion during the collisionally induced dissociation experiments, a prerequisite for the use of automated database searching of uninterpreted tandem mass spectra. The reported approach is outlined for the detection, identification, and characterization of oxylipid peptide conjugates, but the labeling chemistry may also be applicable to other carbonyl-modified proteins.

A series of macrocyclic phenthrolines and a tris(biphenyl)methyl derivative are synthesized. [2]Rotaoxanes with large ring components were synthesized by the template method, and the stability of rotaxanes was examined.

We hereby explore the effects of irradiating DNA polyanions stored in a quadrupole ion trap mass spectrometer with an optical parametric oscillator laser between 250 and 285 nm. We studied DNA 6-20-mer single strands and 12-base pair double strands. In all cases, laser irradiation causes electron detachment from the multiply charged DNA anions. Electron photodetachment efficiency directly depends on the number of guanines in the strand, and maximum efficiency is observed between 260 and 275 nm. Subsequent collision-induced dissociation (CID) of the radical anions produced by electron photodetachment results in extensive fragmentation. In addition to neutral losses, a large number of fragments from the w, d, a *, and z *. ion series are obtained, contrasting with the w and (a-base) ion series observed in regular CID. The major advantage of this technique, coined electron photodetachment dissociation (EPD) is the absence of internal fragments, combined with good sequence coverage. EPD is therefore a highly promising approach for de novo sequencing of oligonucleotides. EPD of nucleic acids is also expected to give specific radical-induced strand cleavages, with conservation of other fragile bonds, including noncovalent bonds. In effect, preliminary results on a DNA hairpin and on double strands suggest that EPD could also be used to probe intra- and intermolecular interactions in nucleic acids.

Some unusual kinetic properties of CoBeII as a result of a complex catalytic pathway that leads in the loss of a metal ion during catalytic turnover, leading to the formation of an inactive enzyme species are reported. This is due to an intrinsic part of the mechanism that needs the bridging hydroxide ion to be consumed during turnover.

The gas-phase acidities of phenol, 3-methylphenol,2,4,6-trimehtylphenol, and ethanoic acid relative to hydrogen cyanide, hydrogen sulfide and the hydroperoxyl radical are measured by energy resolved, competitive threshold collision-induced dissociation (TCID) methods. A gas-phase acidity ladder with interlocking measurements would allow the determination of an absolute [DELTA.sub.acid]H0(C6H5OH) and a derived D298(C6H5O-H) value with higher precision.

The operation mechanism of dipyridyldiketopyrrolopyrrole (DPPP)-based [H.sub.2] sensor is investigated in order to understand the electric-field-assisted dissociation of [H.sub.2] in the presence of Pd or Pt, as well as the carrier generation and carrier determination. The electron conduction is confirmed by the Seebeck effect and the doping is characterized by an instantaneous one, since the doping depends on the ambient [H.sub.2] concentration.

Density functional theory (DFT) is used to study the effect of sulfur on one of the reactions in the Fischer-Tropsch synthesis (FTS), the dissociation of carbon monoxide over iron surfaces. The results have indicated that sulfur influences the CO adsorption and dissociation on Fe(100) electronically, by changing the relative energy of the reactants, products and transition-states levels and by blocking the diffusion of oxygen on the surface.

Density functional theory-based Car-Parrinello molecular dynamics is presented at 300 K of the gas-phased ionized Ala-Ala-[H.sup.+] peptide in trans and cis form in accordance with the IR-MPD experimental studies conducted. The experimental IR-MPD spectrum was found to be in excellent agreement in terms of band positions, band shapes and bandwidth.

We present a method for direct determination of rate constants of complex formation, [k.sub.on], and dissociation, [k.sub.off]. The method is termed plug--plug kinetic capillary electrophoresis (ppKCE). To explain the concept of the method, we consider the formation of a noncovalent complex C between molecules A and B; A is assumed to migrate slower in electrophoresis than B. In ppKCE, a short plug of A is injected into a capillary, followed by a short plug of B. When a high voltage is applied, the electrophoretic zone of B moves through that of A, allowing for the formation of C. When the zones of A and B are separated, C starts dissociating. The features of the resulting electropherogram are defined by both binding and dissociation. We developed a unique mathematical approach that allows finding [k.sub.on] and [k.sub.off] from a single electropherogram without nonlinear regression analysis. The approach uses algebraic functions with the only input parameters from electropherograms being areas and migration times of electrophoretic peaks. In this work, we explain theoretical bases of ppKCE and prove the principle of the method by finding [k.sub.on] and [k.sub.off] for a protein-ligand complex. The unique capability of the method to directly determine both [k.sub.on] and [k.sub.off] along with its simplicity make ppKCE highly attractive to a broad community of molecular scientists.

The fragmentation pathways of protonated arginine, protonated [N.sub.alpha],[N.sub.alpha]-dimethylarginine, the [N.sub.alpha],[N.cub.alpha],[N.sub.alpha]-trimethylarginine ion, three protonated [N.sub.epsilon],[N.sub.epsilon]-dimethyllysines, and three permanent lysine ions in which the charge is fixed by trimethylation is described. The results reveal that in the concomitant eliminations, the dissociating complex is vibrationally hot and the intermediate ion formed by losing CO or C[O.sub.2] can immediately dissociate to eliminate the amine.

Thermally assisted collision-induced dissociation (TA-CID) provides increased dissociation in comparison with CID performed at ambient temperature in a quadrupole ion trap mass spectrometer. Heating the bath/collision gas during CID increases the initial internal energy of the ions and reduces the collisional cooling rate. Thus, using the same CID parameters, the parent ion can be activated to higher levels of internal energy, increasing the efficiency of dissociation and the number of dissociation pathways. The increase in the number of dissociation pathways can provide additional structural information. A consequence of the increase in initial internal energy is the ability to use less power to effect collisional activation. This allows lower [q.sub.z] values to be used and, thus, a greater mass range of product ions to be observed. TA-CID alleviates the problems associated with traditional CID and results in more available information than traditional CID.

The first implementation of infrared multiphoton dissociation (IRMPD) for a hybrid quadrupole time-of-flight (QqTOF) mass spectrometer is reported. Ions were trapped in the radio frequency-only quadrupole (q2), which normally serves as a collision cell, and irradiated by a continuous C[O.sub.2] IR laser. The laser beam was introduced coaxially with the quadrupoles in order to maximize overlap with the ion path. The resolution of the TOF mass analyzer allowed direct charge state determination for fragments smaller than 7 kDa. For larger fragments, the charge state could be assigned using the multiple losses of water, characteristic for IRMPD of proteins. The analytical performance is demonstrated by top-down sequencing of several representative proteins (equine myoglobin, bovine casein, and human insulin and chaperonin 10). Various post-translational modifications such as phosphorylation, acetylation, formation of disulfide bridges, and removal of N-terminal methionine followed by acetylation are detected and characterized. The utility of IRMPD for the analysis of biological samples is demonstrated in a study of a recently identified potential marker for endometrial cancer, chaperonin 10.

The dissociative adsorption and decomposition on a range of metal surfaces of an alkane, an alkene, and an aromatic, all representative of species present in an important technological application, was studied under conditions relevant to selective gas sensing based on solid electrolyte potentiometry. It was found that at 870K, pure polycrystalline Pt surfaces do no discriminate between n-hexane, toluene and 1-butene, however, by varying the composition of polycrystalline bimetallic Pt/Au surfaces, good discrimination between these species can be achieved.

Sequential ion/ion reactions have been used to characterize phosphopeptides present in relatively simple peptide mixtures, including one generated from the tryptic digestion of [alpha]-casein. The phosphopeptides in these mixtures gave rise to either low or no signals via positive ion electrospray ionization. Strong signals, however, were generated in the negative ion mode. An initial ion/ion reaction that employed multiply protonated amino-terminated dendrimers converted phosphopeptide anions to the doubly protonated species. The doubly charged cations were then subjected to ion/ion electron transfer to induce dissociation. Electron-transfer dissociation of doubly positively charged phosphopeptides yields characteristic c-and z-type fragment ions by dissociation of the N-[C.sub.[alpha]] bond along the peptide backbone while preserving the labile posttranslational modifications. These results illustrate the ability to alter ion charge after ion formation and prior to structural interrogation. Phosphopeptides provide an example where it can be difficult to form strong doubly charged cation signals directly when they are present in mixtures, which, as a result, precludes the use of electron-transfer dissociation as a structural probe. The sequential ion/ion reaction process described here, therefore, can provide a new capability for structural interrogation in phosphoproteomics.

The rupture forces between an aptamer (1)-functionalized AFM lip and a thrombin-modified Au surface are analyzed. The rupture force for a single aptamer/thrombin complex is determined as ~4.45 pN. The analysis of the system reveals that the rupture forces correspond to the melting of the G-quadruplex structure of the aptamer bound to the thrombin. This melting of the G-quadruplex leads to the dissociation of the aptamer/thrombin complex.

The dissociation of a Coulomb bounded electron-hole germinate pair at a disordered donor/acceptor (D-A) heterojunction is investigated by extending a previous proposal in the literature and using Monte Carlo simulations. The model explains recent experimental results for organic D-A heterojunction and has important consequences on the design of organic photovoltaic devices.

A study uses ultra-violet (UV)-visible extinction spectroscopy and femtosecond pump-probe transient absorption spectroscopy to investigate the effect of femtosecond laser heating on gold nanoparticles attached to DNA ligands through thiol groups. Results show that femtosecond pulse excitation of the deoxyribonucleic acid (DNA)-modified nanoparticles leads to desorption of the thiolated DNA strands from the nanoparticle surface by the dissociation of the gold-sulfur bond.

An ab initio density functional theory calculations are performed to explore possible catalytic effects on the dissociate chemisorption of hydrogen on a Mg(001) surface when carbon is incorporated into Mg material. The computational results imply that a C atom located initially on an Mg(100) surface can migrate into the subsurface and occupy an fcc interstitial site, with charge transfer to the C atom from neighboring Mg atom.

A full-dimensional ab initio potential energy surface and dipole moment surface for water dimer are presented. The surfaces can dissociate into two water molecules correctly, with equilibrium dissociation energy D(sub e) = 1665.74 cm(super -1).

Quasiclassical trajectories for He +H2 are carried out using the ab intio potential of Boothroyd, Martin, and Peterson are carried out and results for the 348 (v, j) states of H2 are compared to those of the calculations that used the potential of Wilson, Kapral, and Burns. Examined are the cross sections for energy transfer and dissociation, the extent of threshold elevation, and the interconversuion of vibrational and rotational energy.

Neutral steroids have traditionally been analyzed by gas chromatography/mass spectrometry (GC/MS) after necessary derivatization reactions. However, GC/MS is unsuitable for the analysis of many conjugated steroids and those with unsuspected functional groups. Here we describe an alternative analytical method specifically designed for the analysis of oxosteroids and those with a 3[beta]-hydroxy-[[DELTA].sup.5] or 5[alpha]-hydrogen-3[beta]-hydroxy structure. Steroids were derivatized with Girard P (GP) hydrazine to give GP hydrazones, which are charged species and readily analyzed by matrix-assisted laser desorption/ionization mass spectrometry. The resulting [[M].sup.+] ions were then subjected to high-energy collision-induced dissociation on a tandem time-of-flight instrument. The product ion spectra give structurally informative fragment ion patterns. The sensitivity of the analytical method is such that steroid structures can be determined from low-picogram (low-femtomole) amounts of sample. The utility of the method has been demonstrated by the analysis of oxysterols extracted from rat brain.

A new hybrid (AM/MM) method is presented, where the QM part is treated by an initio valence bond (VB) theory. Embedding of the quantum region of each diabatic state separately by treating the electrostatic interaction between QM and MM regions is implemented by this method.

A systematic theoretical study on a series of eleven organoselenium compounds that were chosen as models of biologically relevant compound is conducted. It is observed that the bond dissociation energies of organoselenium molecules have similar behavior and both DFT functionals with a reasonably large basis set produce good results, and the B3PW91 method produces the best agreement with experiment and/or high-level reference values.

Studies of the photodissociation reaction process of C(sub 2)H(sub 4)I(sub 2) in the gas phase and in solution, using ab initio and density functional theory (DFT) methods are carried out. Results show that the bridged conformer of the C(sub 2)H(sub 4)I radical, which lies about 3 kcal/mol lower in energy that the anti form, is dominant both in the gas phase and in the solution phase.

The study of the accurate bond dissociation enthalpies (BDEs) (C-H) values calculated for the C-H bond in the methyl group of toluene and its meta- and para-substituted derivatives are presented. Knowledge of the BDE values of the C-H bonds in toluene and its substitute derivatives can be useful for understanding the chemistry of toluene-like compounds.

Studies is carried out on the energetics and dynamics of unimolecular decompositions of C(sub 70)(super +) and its noble gas endohedral cations, 70)(super +) and 70)(super +). It is discovered that the contribution of encaging the metallic atom to the stability of the fullerene cage toward C(sub 2) loss is much larger than that of encapsulating the noble gas atom.

Study of the photodissociation dynamics of the ethoxy radical at energies from 5.17 to 5.96 eV using photofragment coincidence imaging is presented. It is concluded that the statistical dissociation on the ground-state surface does not occur for any of the observed product channels and that isomerization to CH(sub 2)CH(sub 2)OH prior to OH loss probably occurs on an excited-state surface.

An extended study of ground-state tautomerism and excited-state proton-transfer processes of 2-(6'-hydroxy-2'-pyridyl) benzimidazolium in H(sub 2)O and D(sub 2)O is conducted. It is found that this compound shows in the ground state a tautomeric equilibrium between the lactim form C, protonated at the benzimidazole N(3), and its lactam tautomer TC, obtained by proton translocation from the hydroxyl group to the pyridine nitrogen.

Water dissociation on an oxygen-covered Mo(110) surface was investigated using temperature-programmed reaction spectroscopy and infrared reflectance absorbance spectroscopy. The oxidation of the surface by NO(sub 2) inhibits water dissociation, and the dissociation of NO(sub 2) which yields M(sub o)=O species drives the formation of water from adsorbed OH and desorption of condensed water from the surface and it is suggested that the oxidic property of O(sub 2) results in a lack of activity for the water dissociation.

The local stability of AI atoms replacing Si in the zeolite framework is compared for all inequivalent tetrahedral (T) sites in mordenite, for AI/Si substitutions in two T sites the stable location of the compensating extraframework Zn(super 2+) cation forming a Lewis acid site is determined. The comparison of the two energies of configurations containing two AI and one extraframework Zn(super 2+) cation shows that the stability depends mainly on the location of the AI/Si substitution.

The underlying mechanism of UV light-induced dissociation and visible light-induced reformation of vesicles formed by an azobenzene diblock copolymer was investigated. The study suggests a specific design principle for obtaining UV light-dissociable and visible light-recoverable vesicles based on azobenzene block copolymers.