Separating stereoisomers of di-, tri-, and tetrapeptides using capillary electrophoresis with contactless conductivity detection

The separation and detection of small oligopeptides in CE with contactless conductivity detection were demonstrated. A strongly acidic separation buffer (0.5 M acetic acid) was employed in order to render the species cationic. Separation of the stereoisomers was achieved in typically 10-15 min by using either dimethyl-beta-CD (DM-beta-CD), (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (18C(6)H(4)), a combination of the two substances, or of histidine, as buffer additives. Calibration curves were determined for isomers of Gly-Asp and H-Pro-Asp-NH(2), in the range of 0.05-0.5 mM and 0.1-1 mM, respectively, and were found to be linear. LODs were determined to be in the order of 1.0 microM. The determination of isomeric impurities down to about 1% was found possible. Species showing good separation could also be successfully determined on an electrophoretic lab-on-chip device, with analysis times of a few minutes.     

On the number of significant mode-mode anharmonic couplings in vibrational calculations: Correlation-corrected vibrational self-consistent field treatment of di-, tri-, and tetrapeptides

A computational study is made of the number of important anharmonic mode-mode couplings in the context of vibrational calculations for di-, tri-, and tetrapeptides. The method employed is the correlation-corrected vibrational self-consistent field (CC-VSCF) algorithm, which includes correlation effects between different vibrational modes. It is found that results of good accuracy can be obtained in calculations that include only N log N mode-mode coupling terms, where N is the number of modes. This simplification significantly accelerates CC-VSCF calculations for large molecules. A criterion based on the characteristics of the normal-mode displacements is employed to predict a priori unimportant coupling terms. The criterion is tested statistically using Spearman's rank correlation coefficient. The results are illustrated by calculations for several di-, tri-, and tetrapeptides using semiempirical PM3 potential surfaces. These results are analyzed and a statistical model for error estimation is given. The decrease in the number of included coupling from N(2) to N log N opens possibilities of anharmonic vibrational calculations for large peptides.     

Polyacetylene compounds,derivatives of di-, tri- and tetraphenylethylene

Summary A method was developed for the synthesis of polyacetylenic compounds belonging to the phenyl-substituted ethylene series.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2079–2081, November 1965     

Synthesis of new chiral mono-, di-, tri-, and tetraalkylglycolurils

Two general procedures were developed for the synthesis of chiral N-mono-, N, N′-di-, N, N′ N″-tri-, and N, N′, N″, N′″-tetraalkylglycolurils based on the reactions of 4,5-dihydroxy-imidazolidin-2-ones or glyoxal with one or two moles of alkylureas, respectively, by acid catalysis. The reactions of N-monoalkyl- and N, N′-dialkylureas with glyoxal proceed regioselectively. The mechanism of these reactions was suggested and partly confirmed by quantum-chemical calculations and experimental data. The enantiomeric separation of some chiral glycolurils by chiral-phase HPLC was carried out for the first time.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 680–692, March, 2005.     

Synthesis of di-, tri-, and tetra-substituted carbazole analogs involving annulation methodology

Synthesis of substituted carbazole analogs was achieved via Michael addition followed by intramolecular cyclization and subsequent aromatization.     

Regioselective trapping of terminal di-, tri-, and tetraynes with benzyl azide

[Structure: see text] The reaction of benzyl azide with terminal di-, tri-, and tetraynes appended with a range of functional groups has been explored. Standard reaction conditions for BnN3 catalyzed by CuSO4.5H2O gave alkynyl, butadiynyl, and hexatriynyl triazoles in moderate to good yields. The reaction proceeds regioselectively as determined by the X-ray crystallographic analysis of three derivatives (1c, 1d, and 3c), and no evidence of multiple azide addition to the polyyne framework is observed.     

Determination of acidity of di-, tri-, and tetraazaporphyrins in dimethyl sulfoxide-potassium cryptate medium

Acidic properties of 10,20-diaza-3,7,13,17-tetramethyl-2,8,12,18-tetra-n-hexylporphyrin, 2,7,12,17-tetra-t-butyltetrabenzo-5,10,15-triazaporphyrin and octa(n-amyloxy)phthalocyanine in the system of dimethyl sulfoxide-potassium cryptates (DMSO-K[222]OH) at ambient temperature was investigated by the method of spectrophotometric titration. The porphyrins in the DMSO-K[222]OH medium were shown to dissociate sequentially forming mono- and dianions in two steps. The concentration ranges of existence of the anionic forms and the acidity sequence of the studied meso-aza-substituted porphyrins were investigated.     

Thermospray mass spectrometry of diazonium and di-, tri- and tetra-quaternary onium salts

Various diazonium, multiply charged ammonium and pyridinium salts and one diphosphonium salt have been analysed by thermospray (TSP) mass spectrometry. The intact cation forms the base peak in all spectra. Typically only a few, yet structurally significant, ions are observed. For diazonium salts the level of fragmentation can be controlled by the temperature of the TSP interface while the fragmentation of the quaternary salts is found to be rather insensitive to interface temperatures.     

Intramolecular charge resonance in dimer radical anions of di-, tri-, tetra-, and pentaphenylalkanes

Intramolecular dimer radical anions of di-, tri-, tetra-, and pentaphenylalkanes were investigated on the basis of absorption spectral measurements during γ-radiolysis in 2-methyltetrahydrofuran (MTHF) glassy matrix at 77 K and theoretical calculations. The absorption spectrum of 1,1,2,2-tetraphenylethane (1,1,2,2-Ph(4)E) radical anion showed two bands in the near-infrared (NIR) region (900-2600 nm). One band observed at shorter wavelength than 2000 nm is assigned to the intramolecular charge resonance (CR) band between two phenyl groups of the 1,1-diphenylmethyl chromophore (1,1-dimer radical anion). The intramolecular CR band of the 1,1-dimer radical anion was observed for various alkanes having 1,1-diphenylmethyl chromophore such as 1,1,1-triphenylmethane (1,1,1-Ph(3)M), 1,1,1,1-tetraphenylmethane (1,1,1,1-Ph(4)M), and so on. The other intramolecular CR band observed at longer wavelength than 2200 nm is assigned to intramolecular dimer radical anion between two phenyl groups of the 1,2-diphenylethyl chromophore (1,2-dimer radical anion). The intramolecular CR band of the 1,2-dimer radical anion was observed for various alkanes having a 1,2-diphenylethyl chromophore, such as 1,1,2-triphenylethane (1,1,2-Ph(3)E), 1,1,2,2-Ph(4)E, and 1,1,1,2,2-pentaphenylethane (1,1,1,2,2-Ph(5)E) and so on. No dimer radical anion was observed for 1,n-diphenylalkanes (n > 2) without 1,1-diphenylmethyl chromophore. The relationship between the structure and negative charge delocalization over two phenyl groups connected by an sp(3) carbon is discussed.     

Regiochemically flexible substitutions of di-, tri-, and tetrahalopyridines: the trialkylsilyl trick

[reactions: see text] 2,4-Difluoropyridine, 2,4-dichloropyridine, 2,4,6-trifluoropyridine, 2,4,6-trichloropyridine and 2,3,4,6-tetrafluoropyridine react with standard nucleophiles exclusively at the 4-position under halogen displacement. However, the regioselectivity can be completely reversed if a trialkylsilyl group is introduced in the 5-position of the 2,4-dihalopyridines or in the 3-position of the 2,4,6-trihalopyridines or 2,3,4,6-tetrahalopyridine. Then only the halogen most remote from the bulky silyl unit (at the 2-position in the case of the 2,4-halopyridines, at the 6-position with the other substrates) gets involved in the exchange process. After removal of the silyl protective group the nucleophile is invariably found to occupy the nitrogen-neighboring position.     

Sulfoxides in Julia-Lythgoe olefination: efficient and stereoselective preparation of di-, tri-, and tetrasubstituted olefins

[reaction: see text] A novel modification of the classical Julia-Lythgoe olefination, using sulfoxides instead of sulfones, affords, after in situ benzoylation and SmI2/HMPA- or DMPU-mediated reductive elimination, 1,2-di-, tri-, and tetrasubstituted olefins in moderate to excellent yields and E/Z selectivity. The conditions are mild, and the procedure is broadly applicable.     

4-trans-Amino-proline based di- and tetrapeptides as organic catalysts for asymmetric C–C bond formation reactions

4-trans-Amino-proline based di- and tetrapeptides have been successfully applied as chiral organocatalysts in the enantioselective conjugate addition of nitroalkanes to cyclic enones and the direct aldol reaction. Two 4-trans-amino-proline residues were shown to be sufficient enough to catalyze the conjugate addition reactions with up to 88% ee and up to 100% yield. It has been demonstrated that 4-trans-amino-proline based di- and tetrapeptides are significantly more active than l-proline (at 30 mol %) and can catalyze the direct aldol reaction with good yield and enantioselectivity within 3 h and at lower catalyst loading (5 mol %).     

Solid-phase synthesis of symmetrical 5',5'-dinucleoside mono-, di-, tri-, and tetraphosphodiesters

Four classes of phosphitylating reagents were subjected to reactions with aminomethyl polystyrene resin-bound p-acetoxybenzyl alcohol to yield the corresponding polymer-bound mono-, di-, tri-, and tetraphosphitylating reagents. The solid-phase reagents were reacted with unprotected nucleosides (e.g., thymidine, adenosine, 3'-azido-3'-deoxythymidine, cytidine, or inosine) in the presence of 5-(ethylthio)-1H-tetrazole. Polymer-bound nucleosides underwent oxidation with tert-butyl hydroperoxide, deprotection of cyanoethoxy groups with DBU, and the acidic cleavage, respectively, to afford 5',5'-dinucleoside mono-, di-, tri-, and tetraphosphodiesters in 59-78% yield.     

Pyrimidine derivatives. VI. Synthesis of mono-, di-, tri-, and tetrabromo-substituted pyrimidine derivatives

The following bromo-2,4(1H,3H)-pyrimidinediones possessing a bromo substituent at the 5-position and side chains at the 1- and 6-positions were prepared. The three types of mono-bromo derivatives are: 1-(bromoalkyl)-3,6-dimethyl- 3a-d , 5-bromo-3,6-dimethyl-1-(hydroxyalkyl)- 4a-d , and 1-(acetoxyalkyl)-5-bromo-3,6-dimethyl-2,4(1H,3H)-pyrimidinediones 11a-d . The three types of dibromo derivatives are: 5-bromo-1-(bromoalkyl)-3,6-dimethyl- Sa-d , 1-(acetoxyalkyl)-5-bromo-6-bromomethyl- 8a, 8c , and 8d , and 5-bromo-6-bromomethyl 1-(hydroxyalkyl)-2,4(1H,3H)-pyrimidinediones 9a, 9c , and 9d . Likewise one group of tribromo and one group of tetrabromo derivatives are: 5-bromo-1-(bromoalkyl)-6-bromomethyl -7a-d and 5-bromo-1-(bromoalkyl)-6-dibromomethyl-2,4(1H,3H)-pyrimidinediones 6a-d .     

Ground-state energies of mono-, di-, tri- and tetranegative ions of porphins and their metal complexes

From a range of porphin and metal porphin molecules, mono-, di-, tri- and tetranegative ions can be formed in solution. The disproportionation energies of these ions, measured byHush andClack [6] in dimethylformamide, show similar patterns. For the mononegative and trinegative ions, the disproportion of energies are of comparable magnitudes, but the disproportionation energy of the dinegative ion is 0.3 – 0.4 eV more positive. If it is assumed that the electrons are successively filling the lowest vacant orbital (e _g inD _4h ) these results can be rationalized. In particular, if it is assumed that the dinegative ion is spin-paired, with ground-state electronic symmetryB _1g inD _4h , the average difference of 0.3 – 0.4 eV mentioned above should approximate to twice the exchange integral in the antibondinge _g orbital. Calculation of this integral for a number of porphin structures gives good agreement with experiment.

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Zusammenfassung Von einer Reihe von Porphin- und Metallporphinmolekülen können ein-, zwei-, drei- und vierfach negativ geladene Ionen in Lösung hergestellt werden. Die Disproportionierungsenergien dieser Ionen, vonHush undClack [6] in Dimethylformamid gemessen, zeigen ähnliche Struktur. Für die ein- und dreifach negativ geladenen Ionen ist die Disproportionierungsenergie etwa gleich, dagegen für das zweifach negativ geladene Ion 0,3 – 0,4 eV positiver. Wenn man annimmt, daß die Elektronen nacheinander das tiefste unbesetzte Orbital (e _g inD _4h) auffüllen, können diese Ergebnisse erklärt werden. Wenn man insbesondere annimmt, daß das zweifach negativ geladene Ion als Grundzustand einen Singulettzustand der SymmetrieB _1g inD _4h besitzt, ist die oben erwähnte mittlere Differenz von 0,3 – 0,4 eV angenähert doppelt so groß wie das Austauschintegral im antibindendene _g-Orbital. Berechnung dieses Integrals für eine Anzahl Porphinstrukturen ergibt gute Übereinstimmung mit dem Experiment.

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Résumé Une série de porphines et porphines métallés forment des ions mono-, di, tri- et tétranégatifs en solution. Les énergies de disproportionation dans dimethylformamide, présentant de similitudes [6], sont comparables pour les ions mono- et trinégatifs, mais 0,3 – 0,4 eV plus positif pour l'ion dinégatif. Ces résultats sont compréhensibles dans un schéma où les électrons occupent successivement l'orbitale vide la plus basse (e _g en symétrieD _4h ). En particulier, si l'on adopte l'état fondamentalB _1g (enD _4h) aux spins antiparallèles, pour l'ion dinégatif, les 0,3 – 0,4 eV valent approximativement deux fois l'intégrale d'échange pour l'orbitalee _g antiliante. Le calcul de cette intégrale pour une série de porphines s'accorde bien à l'expérience.

     

Di-2-pyridyl ketone oxime in copper chemistry: di-, tri-, penta- and hexanuclear complexes

The use of di-2-pyridyl ketone oxime (Hpko)/X- "blends" (X- = OH-, Cl-, ClO4-) in copper chemistry has yielded neutral binuclear and cationic trinuclear, pentanuclear or hexanuclear complexes. Various synthetic procedures have led to the synthesis of compounds [Cu5(pko)7].[ClO4]3.2CH3OH.2H2O (1), [Cu3(pko)3(OH)(Cl)]2[Ph4B]2.4DMF.2H2O (2), [Cu2(pko)4] (3), {[Cu6(pko)6ClO4(CH3CN)6][Cu6(pko)6(ClO4)3(CH3CN)4]}.8ClO4.14CH3CN.H2O (4). The structures of the complexes have been determined by single-crystal X-ray crystallography.     

Dissociation dynamics of sequential ionic reactions: heats of formation of tri-, di-, and monoethylphosphine

The sequential ethene (C2H4) loss channels of energy-selected ethylphosphine ions have been studied using threshold photoelectron photoion coincidence (TPEPICO) spectroscopy in which ion time-of-flight (TOF) distributions are recorded as a function of the photon energy. The ion TOF distributions and breakdown diagrams have been modeled in terms of the statistical RRKM theory for unimolecular reactions, providing 0 K dissociation onsets, E0, for the ethene loss channels. Three RRKM curves were used to model the five measurements, since two of the reactions differ only by the internal energy of the parent ion. This series of dissociations provides a detailed check of the calculation of the product energy distribution for sequential reactions. From the determined E0's, the heats of formation of several ethylphosphine neutrals and ions have been determined: Delta(f)H degrees 298K[P(C(2)H(5))3] = -152.7 +/- 2.8 kJ/mol, Delta(f)H degrees 298K[P(C(2)H(5))3+] = 571.6 +/- 4.0 kJ/mol, Delta(f)H degrees 298K[HP(C(2)H(5))2] = -89.6 +/- 2.1 kJ/mol, Delta(f)H degrees 298K[HP(C(2)H(5))2+] = 669.9 +/- 2.5 kJ/mol, Delta(f)H degrees 298K[H(2)PC(2)H(5)] = -36.5 +/- 1.5 kJ/mol, Delta(f)H degrees 298K[H(2)PC(2)H(5)+] = 784.0 +/- 1.9 kJ/mol. These values have been supported by G2 and G3 calculations using isodesmic reactions. Coupled cluster calculations have been used to show that the C2H4 loss channel, which involves a hydrogen transfer step, proceeds without a reverse energy barrier.     

Conformational studies by dynamic NMR—28 : Stereomutations in some di-, tri- and tetraalkylhydrazines

Low temperature NMR spectra allowed us to “freeze” some of the internal motions in a number of di-, tri- and tetraalkylhydrazines and to measure the corresponding free energies of activation. In particular, tetramethylhydrazine (Me₂N-NMe₂) was found to have, at - 150°, two pairs of diastereotopic methyls : this is due to the fact that both N-inversion and N,N-rotation are slow at this temperature and that a gauche conformation is adopted. The observed barrier (6.0 kcal mol^-1) has been attributed to N,N-rotation, the barrier due to N-inversion being higher and not measurable via NMR in the presence of a concomitant fast rotation. In other cases, notably PrⁱMeN-NH₂, Me₂N-NPrⁱ₂ and Prⁱ₂N-NHMe, two different motions (inversion and rotation) were detected. In the case of Me₂N-NHMe it was also possible to observe the first example of anisochronous behaviour of nitrogen-bonded methyls (Me₂N) induced by an aminic nitrogen that becomes chiral at low temperature.