Open-shell localized Hartree-Fock method based on the generalized adiabatic connection Kohn-Sham formalism for a self-consistent treatment of excited states

An effective exact-exchange Kohn-Sham approach for the treatment of excited electronic states, the generalized adiabatic connection open-shell localized Hartree-Fock (GAC-OSLHF) method is presented. The GAC-OSLHF method is based on the generalized adiabatic connection Kohn-Sham formalism and therefore capable of treating excited electronic states, which are not the energetically lowest of their symmetry. The method is self-interaction free and allows for a fully self-consistent computation of excited valence as well as Rydberg states. Results for atoms and small- and medium-size molecules are presented and compared to restricted open-shell Hartree-Fock (ROHF) and time-dependent density-functional results as well as to experimental data. While GAC-OSLHF and ROHF results are quite close to each other, the GAC-OSLHF method shows a much better convergence behavior. Moreover, the GAC-OSLHF method as a Kohn-Sham method, in contrast to the ROHF approach, represents a framework which allows also for a treatment of correlation besides an exchange by appropriate functionals. In contrast to the common time-dependent density-functional methods, the GAC-OSLHF approach is capable of treating doubly or multiply excited states and can be easily applied to molecules with an open-shell ground state. On the nodal planes of the energetically highest occupied orbital, the local multiplicative GAC-OSLHF exchange potential asymptotically approaches a different, i.e., nonzero, value than in other regions, an asymptotic behavior which is known from exact Kohn-Sham exchange potentials of ground states of molecules.     

Cyclic esters of aliphatic diacids with pyrocatechol and hydroquinone

Cyclic esters of adipic acid, suberic acid and sebacic acid were prepared by reaction of the acid dichlorides and pyrocatechol or hydroquinone in benzene under high dilution conditions. While only the cyclic dimers could be obtained from hydroquinone, pyrocatechol formed cyclic monomers as well as cyclic dimers (and also a cyclic dimer with succinic acid). The structure of all compounds was confirmed by¹H-NMR- and mass spectra. The crystal structures of the pyrocatechol esters were determined by single crystal X-ray analysis.

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Cyclische Ester aliphatischer Dicarbonsäuren mit Brenzcatechin und Hydrochinon

Zusammenfassung Es wurden cyclische Ester von Adipinsäure, Korksäure und Sebacinsäure durch Reaktion der entsprechenden Säure-Dichloride mit Brenzcatechin oder Hydrochinon bei hoher Verdünnung hergestellt. Während mit Hydrochinon lediglich die cyclischen Dimeren erhalten werden konnten, wurden mit Brenzcatechin sowohl cyclische Monomere als auch cyclische Dimere erhalten (ebenfalls das cyclische Dimer mit Bernsteinsäure). Die Strukturen wurden mittels¹H-NMR und Massenspektren gesichert. Die Kristallstrukturen der Brenzcatechin-Ester wurden mittels Röntgenstrukturanalyse bestimmt.

     

Direct identification of all oncogenic mutants in KRAS exon 1 by cycling temperature capillary electrophoresis

Over the past few decades, advances in genetics and molecular biology have revolutionized our understanding of cancer initiation and progression. Molecular progression models outlining genetic events have been developed for many solid tumors, including colon cancer. Previous reports in the literature have shown a relationship between different KRAS mutations and prognosis and response to medical treatment in colon cancer patients. Furthermore, the presence of a mutated KRAS has been correlated with different clinicopathological variables including age and gender of patients and tumor location. To our knowledge, few institutions screen for KRAS mutations on regular basis in colon cancer patients despite such evidence that knowledge of KRAS exon 1 status is informative. Here, we report on a mutation analysis method adapted to a 96-capillary electrophoresis instrument that allows identification of all 12 oncogenic mutations in KRAS exon 1 under denaturing conditions. To determine the optimal parameters, a series of DNA constructs generated by site-directed mutagenesis was analyzed and the migration times of all mutant peaks were measured. A classification tree was then made based on the differences in migration time between the mutants and an internal standard. A randomized series of 500 samples constructed with mutagenesis as well as 60 blind samples from sporadic colon carcinomas was analyzed to test the method. No wild-type samples were scored as mutants and all mutants were correctly identified. Post polymerase chain reaction (PCR) analysis time of 96 samples was performed within 40 min.     

Yellowing and IR-changes of spruce wood as result of UV-irradiation

The yellowing and IR-changes of spruce wood as a result of UV-irradiation were studied using two different types of xenon lamps (lambda>300 nm; I(o)=50 mW cm(-2) and lambda>280 nm; I(o)=17.5 mW cm(-2)). Changes in the IR spectra as well as the yellowing of the irradiated wood surfaces show the influence of UV light on the wood modules. The UV-irradiation (72 h; lambda>300 nm; I(o)=50 mW cm(-2)) decreased the lignin content on the surface by up to 20% of the original values. The colour difference of yellowing (deltaE) exhibited a systematic trend to higher values with increasing irradiation time. Our results show that the photoyellowing (UV-Vis detection) correlates very well with lignin degradation (IR detection). This result is in agreement with the quinone formation as the chromophoric reaction product of lignin decay. The degradation, yellowing, and oxidation kinetics differed only little using different light sources. The absorbed light intensity, which depends on wavelength, the intensity distribution of the light source and the absorption spectrum of lignin, influenced the degradation rate. Under the current experimental conditions, the absorption spectrum of lignin was the most important factor. Therefore, irradiation with lambda>280 nm is useful for rapidly monitoring the UV-degradation of wood     

Experimental evidence for multiple oxidation pathways in the (salen) Mn-catalyzed epoxidation of alkenes

The substrate electronic effects on the selectivity in the catalytic epoxidation of para-substituted cis stilbenes 2a-i were investigated by using (R,R)-[N,N'-bis(3,5-di-tBu-salicylidene)-1,2-cyclohexanediamine]manganese(III) chloride 1 in benzene as the catalyst with iodosobenzene as the terminal oxidant. A Hammett study of the selectivity results reveals a stronger electrophilic character than previously assumed in the (salen)Mn-catalyzed reaction. In general, the best correlations with the experimental values were obtained by using the Hammett sigma + values, which gave rho = -1.37 for the rate of cis-epoxide formation and rho = -0.43 for the rate of the stepwise process leading to the corresponding trans product. The reaction involves two separate pathways as indicated also by the competitive breakdown of the intermediate on the path to trans epoxide for methoxy-substituted substrates. The asynchronicity in the concerted pathway leading to cis epoxide is apparent for 4-methoxy-4'-nitrostilbene, which yields cis epoxide with 75% ee entirely as a result of electronic effects.     

Homogeneous sample preparation for automated high throughput analysis with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry

This work presents a simple method for obtaining homogeneous sample surfaces in matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOFMS) for the automated analysis of peptides and proteins. The sample preparation method is based on applying the sample/matrix mixture onto a pre-deposited highly diluted matrix spot. The pre-deposited crystals act as seeds for the new sample containing crystals which become much smaller in size and more evenly distributed than with conventional methods. This 'seed-layer' method was developed, optimised and compared with the dried-droplet method using peptides and proteins in the 1000-20,000 Da range. The seed-layer method increases the surface homogeneity, spot to spot reproducibility and sample washability as compared with the commonly used dried-droplet method. This methodology is applicable to alpha-cyanohydroxycinnamic acid, sinapinic acid and ferulic acid, which all form homogeneous crystal surfaces. Within-spot variation and between-spot variation was investigated using statistics at a 95% confidence level (n = 36). The statistical values were generated from more than 5000 data points collected from 500 spectra. More than 90% of the sample locations results in high intensity spectra with relatively low standard deviations (RSDs). Typically obtained data showed an RSD of 19-35% within a sample spot as well as in-between spots for proteins, and an RSD of < or = 50% for peptides. Linear calibration curves were obtained within one order of magnitude using internal calibration with a point-RSD of 3% (n = 10). The sample homogeneity allows mass spectra (average of 16 laser shots) to be obtained on each individual sample within 15 sec, whereby a 100 spot target plate can be run in 25 min. High density target plates using the seed-layer method were prepared by spotting approximately 100 picoliter droplets onto the target, resulting in sample spots < or = 500 microns in diameter using a flow-through piezo-electric micro-dispenser. By using this automated sample preparation step lower standard deviations are obtained in comparison to manually prepared samples.     

Phospholes with Reduced Pyramidal Character from Steric Crowding. 2. Photoelectron Spectral Evidence for Some Electron Delocalization in 1-(2,4-Di-tert-butyl-6-methylphenyl)-3-methylphosphole

Photoelectron spectroscopy has been explored as a tool to measure the flattening of the phosphorus pyramid in a phosphole as caused by a large, sterically demanding P-substituent. Earlier PE spectra had shown no difference in ionization energies (IE) for simple phospholes and their tetrahydro derivatives (both around 8.0-8.45 eV). Calculations of the Koopmans IE at the Hartree-Fock 6-31G level for 1-methylphospholane showed that, as is known for nitrogen, planarization at phosphorus markedly reduced the ionization energy value (8.74 to 6.29 eV). A reduction in IE also occurred on planarizing 1-methylphosphole, but to a lesser extent, being offset by increased electron delocalization (8.93 to 7.16 eV). This suggests that experimental comparison of IE for the unsaturated and saturated systems could be used to detect the presence of electron delocalization in the former. The IE experimentally determined for the crowded 1-(2,4-di-tert-butyl-6-methylphenyl)-3-methylphosphole was 7.9 eV, the lowest ever recorded for a phosphole. The corresponding phospholane had IE 7.55 eV. The difference in the values is attributed to electron delocalization in the phosphole. Calculations performed on the related model 1-(2-tert-butyl-4,6-dimethylphenyl)phosphole showed that the P-substituent adopted an angle of 55.7 degrees (DFT/6-31G level; 57.6 degrees at the HF/6-31 level) with respect to the C(2)-P-C(5) plane (for P-phenyl, 67.1 degrees and 68.3 degrees, respectively).     

Thermische Umlagerung von Acetoxy-cyclohexadienonen, 2. Mitt.

Zusammenfassung Es wird die Frage untersucht, ob bei der thermischen Umlagerung von entsprechend allyl-substituierten o-Benzochinol-acetaten der Allyl- oder der Acetoxylrest rascher wandert. Das 2-Allyl-2-acetoxy-cyclohexadienon liefert bei der genannten Reaktion (es sind schon Temperaturen um 100° ausreichend) überwiegend ein Monoacetat des 4-Allylbrenzcatechins. Damit ist bewiesen, daß der Rest rascher als der Rest in die p-Stellung zur Carbonylgruppe des Chinolacetates wandert. Eine Wanderung des Acetoxylrestes in die o- oder in die p-Stellung zur Carbonylgruppe, welche zur Bildung von 3-Allyl-brenzcatechin bzw. 2-Allylhydrochinon führen müßte, konnte nicht beobachtet werden. Entsprechend liefert das 2,6-Diallyl-2-acetoxy-cyclohexadienon bei der thermischen Umlagerung überwiegend ein Monoacetat des 3,5-Diallyl-brenzcatechins. Nach einem anderen Mechanismus verläuft die Umlagerung des 2-Methyl-6-allyl-2-acetoxy-cyclohexadienons. Es entsteht neben wenig 2-Methyl-6-allyl-hydrochinon in der Hauptmenge ein Monoacetat des 3-Methyl-5-allyl-brenzcatechins. Es wird also die Allylgruppe durch den in die o-Stellung wandernden Acetoxylrest verdrängt. Auf diese Reaktion wird näher eingegangen, weil sie in engem Zusammenhang mit der Frage steht, ob ganz allgemein eine Umlagerung von o-Chinolacetaten vom Typ in die Isomeren möglich ist.Mit 2 AbbildungenHerrn Prof. Dr.F. Feigl zum 70. Geburtstag in alter Freundschaft!F. W. E. Zbiral, F. Wessely undE. Lahrmann, (gilt als 1. Mitt. dieser Reihe), Mh. Chem.91, 331 (1960).