Rate constants from the reaction path Hamiltonian. I. Reactive flux simulations for dynamically correct rates

As ab initio electronic structure calculations become more accurate, inherent sources of error in classical transition state theory such as barrier recrossing and tunneling may become major sources of error in calculating rate constants. This paper introduces a general method for diabatically constructing the transverse eigensystem of a reaction path Hamiltonian in systems with many degenerate transverse frequencies. The diabatically constructed reaction path Hamiltonian yields smoothly varying coupling constants that, in turn, facilitate reactive flux calculations. As an example we compute the dynamically corrected rate constant for the chair to boat interconversion of cyclohexane, a system with 48 degrees of freedom and a number of degenerate frequencies. The transmission coefficients obtained from the reactive flux simulations agree with previous results that have been calculated using an empirical potential. Furthermore, the calculated rate constants agree with experimental values. Comparison to variational transition state theory shows that, despite finding the true bottleneck along the reaction pathway, variational transition state theory only accounts for half of the rate constant reduction due to recrossing trajectories.     

Complex formation of isocytosine tautomers with PdII and PtII

Isocytosine (ICH) exists in solution as two major tautomers, the keto form with N1 carrying a proton (1a) and the keto form with N3 being protonated (1b). In water, 1a and 1b exist in equilibrium with almost equal amounts of both forms present. Reactions with a series of Pd(II) and Pt(II) am(m)ine species such as (dien)Pd(II), (dien)Pt(II), and trans-(NH(3))(2)Pt(II) reveal, however, a distinct preference of these metals for the N3 site, as determined by (1)H NMR spectroscopy. Individual species have been identified by the pD dependence of the ICH resonances. pK(a) values (calculated for H(2)O) for deprotonation of the individual tautomers complexes are 6.5 and 6.4 for the N3 linkage isomers of dienPd(II) and dienPt(II), respectively, as well as 6.2 and 6.0 for the N1 linkage isomers. The dimetalated species [(dienM)(2)(IC-N1,N3)](3+) (M = Pd(II) or Pt(II)) are insensitive over a wide range of pD. The crystal structure analysis of [(dien)Pd(ICH-N3)](NO(3))(2) is reported. Ab initio calculations have been performed for tautomer compounds of composition [(NH(3))(3)Pt(ICH)](2+), cis- and trans-[(NH(3))(2)PtCl(ICH)](+), as well as trans-[(NH(3))(2)Pt(ICH)(2)](2+). Without exception, N3 linkage isomers are more stable, in agreement with experimental findings. As to the reasons for this binding preference, an NBO (natural bond orbital) analysis for [(NH(3))(3)Pt(ICH-N3)](2+)strongly suggests that intramolecular hydrogen bonding between trans-positioned NH(3) ligands and the two exocyclic groups of the ICH is of prime importance. The calculations furthermore show a marked pyramidalization of the NH(2) group of ICH in the complex once the heterocyclic ligand forms a dihedral angle <90 degrees with the Pt coordination plane.     

Untersuchungen über Enzymaktivitäten der Leberzelle bei Vitamin-E-Mangel

The enzymatic elongation of acyl-CoA esters by malonyl-CoA, respectively de novo synthesis of fatty acids from malonyl-CoA by liver microsomes and non particulate fraction of α-tocopherol deficient rats is diminished versus controls. However, liver microsomes of vitamin E deficient rats synthesize more eicosatetraenic acid from γ-linolenic acid and more γ-linolenic acid from linolic acid than do those of tocopherol supplemented animals. It has often been shown that the liver phosphatides of tocopherol deficient rats contain more arachidonic acid than those of controls, a fact which can be explained now by increased activity of the enzymes involved in the biosynthesis of arachidonic acid. Certain polyenic fatty acids are more rapidly synthesized in the absence of naturally occuring antioxidants. Some enzymes of the respiratory chain have also been examined. No vitamin E deficiency effect has been found on enzymes such as gluconate-6-P-dehydrogenase, isocitrate-dehydrogenase, malate-dehydrogenase and lactate dehydrogenase contained in the non particulate fraction. Sonicated mitochondria of tocopherol deficient rats show a greater activity towards cytochrome, oxydase and β-hydroxy-acetyl-CoA-dehydrogenase than controls, possibly due to ultrastractural alteration of this particle.     

Calculation of the frequencies and intensities in the infrared and raman spectra of cyclopropenone

By using the values of the vibrational frequencies of normal and deuterated cyclopropenone (II-d₀ , II-d₂ ) and ¹⁶ O-and ¹⁸ O-substituted dimethylcyclopropenone (III) as -well as the infrared and Raman intensities of II a consistent set of force constants has been derived for the cyclopropenone skeleton. The derived values show that the zwitterionic form makes a substantial contribution to the electronic ground state of the molecule. The combined frequency and intensity calculation - simulation of the infrared and the Raman spectrum - is shown to be a good method for making a proper assignment of calculated and observed vibrations and deriving realistic sets of force constants.     

An improved method for the synthesis of cellulose membrane-bound peptides with free C termini is useful for PDZ domain binding studies

SPOT synthesis permits parallel synthesis and screening of thousands of cellulose membrane-bound peptides to study protein-protein interactions in a proteomic context. Recognition of C-terminal residues is one of the most common binding features of PDZ domains. Unfortunately, most solid support-bound peptide libraries lack a free C terminus due to C-terminal fixation on the solid support. To overcome this restriction, we developed a robust methodology based on our previous strategy for generating peptides with authentic C termini. To validate this improved method, we screened a human peptide library of 6223 C termini with the syntrophin PDZ domain. Furthermore, using the same library, new peptide ligands derived from membrane proteins and receptors were found for the ERBIN PDZ domain. Finally, we identified the protein kinase breakpoint cluster region, which is known as a negative regulator of cell proliferation and oncogenic transformation, as an ERBIN ligand.     

Reaktionen von tBuPLi2 mit Carbodiimiden

Reaction of ^tBuPLi₂ with Carbodiimides The reaction of bis(cyclohexyl)carbodiimide with ^tBuPLi₂ in THF at 20 °C leads to the tetranuclear Li‐complex [Li₄(THF)₂{^tBuP([^cHexN]₂C)₂}₂] ( 1 ). No addition on the carbodiimide but a silyl transfer was observed under similar conditions during the treatment of bis(trimethylsilyl)carbodiimide with ^tBuPLi₂ to give the lithium salts ^tBuP(SiMe₃)Li and [Li(THF)(Me₃SiN‐C≡N)]_n ( 2 ). 1 was characterized by NMR, IR and RE spectroscopy, mass spectrometry and X‐ray analyses. Theoretical calculations were performed for 1 . According to the structural investigations 1 consists ofa central centrosymmetrical twelve‐membered Li₂N₄C₄P₂ ring adjacent by two six‐membered LiN₂C₂P rings. The peripheric Li⁺ cations posssess coordination number (cn) 3 buildt‐up by two N atoms and a THF ligand, while the two central Li⁺ cations possess only cn 2. However, the theoretical calculations have shown no relevant bonding Li···Li or Li···P interaction.     

Absolute Rate Constants for the Addition of the 1‐(tert‐Butoxy)carbonylethyl Radical onto Cyclic Alkenes in Solution

Absolute rate constants are reported for the addition of the 1‐[(tert‐butoxy)carbonyl]ethyl (= 2‐(1,1‐dimethylethoxy)‐1‐methyl‐2‐oxoethyl) radical ^.CHMeCO₂(t‐Bu) to several cyclic and monosubstituted alkenes in MeCN as obtained by time‐resolved electron paramagnetic resonance (EPR). The activation energies for the addition of this alkyl radical are mainly governed by the addition enthalpy but are also substantially lowered by the ambiphilic effect and by relief of cyclic strain.     

Screening, library-assisted identification and validated quantification of 23 benzodiazepines, flumazenil, zaleplone, zolpidem and zopiclone in plasma by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization

A liquid chromatographic/mass spectrometric assay with atmospheric pressure chemical ionization (LC/APCI-MS) is presented for fast and reliable screening and identification and also for precise and sensitive quantification in plasma of the 23 benzodiazepines alprazolam, bromazepam, brotizolam, camazepam, chlordiazepoxide, clobazam, clonazepam, diazepam, flunitrazepam, flurazepam, desalkylflurazepam, lorazepam, lormetazepam, medazepam, metaclazepam, midazolam, nitrazepam, nordazepam, oxazepam, prazepam, temazepam and tetrazepam, triazolam, their antagonist flumazenil and the benzodiazepine BZ1 (omega 1) receptor agonists zaleplone, zolpidem and zopiclone. It allows confirmation of the diagnosis of an overdose situation and monitoring of psychiatric patients' compliance. The analytes were isolated from plasma using liquid-liquid extraction and were separated on a Merck LiChroCART column with Superspher 60 RP Select B as the stationary phase. Gradient elution was performed using aqueous ammonium formate and acetonitrile. After screening and identification in the scan mode using the authors' LC/MS library, the analytes were quantified in the selected-ion monitoring mode. The quantification assay was fully validated. It was found to be selective proved to be linear from sub-therapeutic to over therapeutic concentrations for all analytes, except bromazepam. The corresponding reference levels the assay's accuracy and precision data for all studied substances are listed. The accuracy and precision data were within the required limits with the exception of those for bromazepam. The analytes were stable in frozen plasma for at least 1 month. The validated assay was successfully applied to several authentic plasma samples from patients treated or intoxicated with various benzodiazepines or with zaleplone, zolpidem or zopiclone. It has proven to be appropriate for the isolation, separation, screening, identification and quantification of the drugs mentioned above in plasma for clinical toxicology, e.g. in cases of poisoning, and forensic toxicology, e.g. in cases of driving under the influence of drugs.     

Diorganogalliumfluoride. Die Kristallstruktur des Mischkristalls [B(CH2Ph)3]0,92[Ga(CH2Ph)3]0,08 · NCMe

Diorganogallium Fluorides. The Crystal Structure of the Mixed Crystal [B(CH₂Ph)₃]_0.92[Ga(CH₂Ph)₃]_0.08 · NCMe The reaction of GaR₃ with BF₃ · OEt₂ in diethylether leads to the diorganogallium fluorides R₂GaF [R = i-Pr ( 1 ), CH₂Ph ( 2 ), Mes ( 3 )]. Compound 1 is also available by the reaction of i-Pr₂GaBr ( 6 ) with KF at ?20°C in acetonitrile. The by-product B(CH₂Ph)₃, formed together with 2 during the first reaction, crystallizes with ca. 8% Ga(CH₂Ph)₃ in acetonitrile as [B(CH₂Ph)₃]_0.92[Ga(CH₂Ph)₃]_0.08 · NCMe ( 4 ) in the space group P2₁/n with a = 1050.32(7) pm, b = 1159.5(2) pm, c = 1591.6(1) pm and β = 96.931(6)°.     

Laser desorption mass spectrometry on thin liquid jets

A recently developed soft desorption method for mass spectrometry is presented, which is called Laser Induced Liquid Beam Ionization/Desorption (LILBID). Analyte ions are desorbed from a thin jet of analyte solution directly into vacuum by means of an IR laser pulse, which has been tuned to a vibrational resonance of the solvent. A comparative experiment with ammonium chloride and aniline hydrochloride shows that ion formation via proton transfer takes place in the solution. Thermally unstable compounds, as well as supra- and biomolecular complexes, can be detected intact and mass analyzed in a reflectron time-of-flight (Re-TOF) mass spectrometer. During the desorption process, noncovalent interactions and some solvation characteristics are preserved. Three examples for the capacity of LILBID are given in this short overview: (a) ion-solvent interactions with the formation of a clathrate structure Cs⁺(H₂O)₂₀, (b) host-guest interactions with the K⁺ selectivity of valinomycin, and (c) noncovalent interactions with the dimerization of gramicidin. Received: 29 July 1997 / Revised: 4 September 1997 / Accepted: 12 September 1997