A stereoelectronic effect on turn formation due to proline substitution in elastin-mimetic polypeptides

Stereoelectronic effects have been identified as contributing factors to the conformational stability of collagen-mimetic peptide sequences. To assess the relevance of these factors within other protein structural contexts, three polypeptide sequences were prepared in which the sequences were derived from the canonical repeat unit (Val-Pro-Gly-Val-Gly) of the protein material elastin. These elastin-mimetic polypeptides, elastin-1, elastin-2, and elastin-3, incorporate (2S)-proline, (2S,4S)-4-fluoroproline, and (2S,4R)-4-fluoroproline, respectively, at the second position of the elastin repeat. Calorimetric and spectroscopic investigations of these three polypeptides indicate that the incorporation of the substituted proline residues had a dramatic effect upon the self-assembly of the corresponding elastin peptide. The presence of (2S,4R)-4-fluoroproline in elastin-3 lowered the temperature of the phase transition and increased the type II beta-turn population with respect to the parent polypeptide, while the presence of (2S,4S)-4-fluoroproline in elastin-2 had the opposite effect. These results suggest that stereoelectronic effects could either enhance or hinder the self-assembly of elastin-mimetic polypeptides, depending on the influence of the proline analogue on the energetics of the beta-turn conformation that develops within the pentapeptide structural repeats above the phase transition. Density functional theory (DFT) was employed to model three possible turn types (betaI-, betaII-, and inverse gamma-turns) derived from model peptide segments (MeCO-Xaa-Gly-NHMe) (Xaa = Pro, 4S-F-Pro, or 4R-F-Pro) corresponding to the turn-forming residues of the elastin repeat unit (Val-Pro-Gly-Val-Gly). The results of the these calculations suggested a similar outcome to the experimental data for the elastin-mimetic polypeptides, in that type II beta-turn structures were stabilized for peptide segments containing (2S,4R)-fluoroproline and destabilized for segments containing (2S,4S)-fluoroproline relative to the canonical proline residue.     

The Reactivity of Bis(para‐methoxyphenyl)telluroxide towards Triflic Acid and Diphenylphosphinic Acid. Theoretical Considerations of the Protonation and Hydration Process of Diorganotelluroxanes

The reaction of (p‐MeOC₆H₄)₂TeO with two equivalents of HO₃SCF₃ and HO₂PPh₂ provided the tetraorganoditelluroxanes (F₃CSO₃)(p‐MeOC₆H₄)₂TeOTe(p‐MeOC₆H₄)₂(O₃SCF₃) ( 1 ) and (Ph₂PO₂)(p‐MeOC₆H₄)₂TeOTe(p‐MeOC₆H₄)₂(O₂PPh₂)·2 Ph₂PO₂H ( 2 ) in good yields. Compounds 1 and 2 were characterized by solution and solid‐state ³¹P and ¹²⁵Te NMR spectroscopy, IR spectroscopy, electrospray mass spectrometry, conductivity measurements and single crystal X‐ray diffraction. In solution, compound 1 undergoes an electrolytic dissociation and reversibly reacts with traces of water to give the mononuclear cation [(p‐MeOC₆H₄)₂TeOH]⁺ and triflate anions. Theoretical aspects of the protonation and hydration of model telluroxanes R₂TeO (R = H, Me, Ph) were investigated by preliminary DFT calculations and compared to the corresponding selenoxanes R₂SeO. The tellurium dihydroxides R₂Te(OH)₂ seem to be more stable than the hydrogen‐bonded complexes R₂TeO·H₂O.     

Diastereoselective intermolecular rhodium-catalyzed [4 + 2 + 2] carbocyclization reactions: computational and experimental evidence for the intermediacy of an alternative metallacycle intermediate

Intermolecular rhodium-catalyzed [m + n + o] reactions of 1,6-enynes and various pi-components (carbon monoxide, alkynes, 1,3-butadienes, etc.) provide an expeditious approach for the construction of polycyclic fragments that represent important synthons for target-directed synthesis. We present computational and experimental evidence for the existence of a previously undescribed reaction pathway for the rhodium-catalyzed [4 + 2 + 2] reaction involving a 1,6-enyne. This model clearly demonstrates the origin of the excellent diastereoselectivity in this type of reaction and the remarkable tolerance of both (E)- and (Z)-isomers within the 1,6-enyne, which is generally prone to competitive ene-cycloisomerization.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 11. Synthesis and total assignment of the 1H and 13C NMR spectra of isomeric benzothienonaphthoquinolines using multiple inverse detected two-dimensional NMR methods

Two novel heterocyclic ring systems, namely, [1]benzothieno[2,3-c]naphtho[1,2-f]quinoline and [1]benzothieno[2,3-c]naphtho[2,1-g]quinoline have been synthesized and characterized by inverse detected two-dimensional nmr methods. Unequivocal total assignments of the proton and carbon nmr spectra were made through the concerted utilization of HMQC (Heteronuclear Multiple Quantum Correlation) and a combination of HMBC (Heteronuclear Multiple Bond Correlation) and HMQC-TOCSY (HMQC with proton TOtal Correlation Spectroscopy).     

An NMR study of the species produced by the reactions of dialkyl magnesium and HCl with calcined silica and the polymerisation performance of Ziegler-Natta catalysts produced from this support material

The effect of calcinations on the silica surface groups and thereby on the activity of Ziegler-Natta catalysts in ethylene homopolymerisation has been studied. Silica was calcined at different temperatures and treated with MgR₂ and HCl. Silica surface groups were identified by using ¹H MAS NMR and ¹³C and ²⁹Si CP MAS NMR techniques. Magnesium, titanium and chlorine were measured by elemental analysis. Ziegler-Natta catalysts were prepared from these supports and subsequently used in ethylene homopolymerisation. Maximum activity was obtained with the catalyst based on 590 °C calcined silica. The results indicate that MgR₂ reacts with siloxane-groups (Si-O-Si) in the 300 °C calcined silica, leaving the hydrogen-bonded hydroxyl-groups unreacted. Low activity Si-O-Ti(Cl)₂-O-Si species are formed after reacting with TiCl₄. The higher activity in the catalyst based on 590 °C calcined silica can be explained by the formation of -Si(R)-O-Si-O-TiCl₃ groups, originating from the siloxane bridges which cannot form in 300 °C calcined silica. Other explanations for the higher activity are a higher Mg/Ti ratio or small amounts of crystal water formed in the 590 °C calcined silica.     

Unraveling the crystallization mechanism of CoAPO-5 molecular sieves under hydrothermal conditions

The hydrothermal crystallization of CoAPO-5 molecular sieves has been studied using time-resolved in-situ SAXS/WAXS, UV-vis, Raman, and XAS. Data collected during heating to 180 degrees C allowed the observation of different steps occurring during the transformation of the amorphous gel into a crystalline material from a macroscopic and atomic perspective. Raman spectroscopy detected the initial formation of Al-O-P bonds, whereas SAXS showed that these gel particles had a broad size distribution ranging from ca. 7 to 20 nm before crystallization began. WAXS showed that this crystallization was sharp and occurred at around 160 degrees C. Analysis of the crystallization kinetics suggested a one-dimensional growth process. XAS showed that Co(2+) transformed via a two-stage process during heating involving (i) a gradual transformation of octahedral coordination into tetrahedral coordination before the appearance of Bragg peaks corresponding to AFI, suggesting progressive incorporation of Co(2+) into the poorly ordered Al-O-P network up to ca. 150 degrees C, and (ii) a rapid transformation of remaining octahedral Co(2+) at the onset of crystallization. Co(2+) was observed to retard crystallization of AFI but provided valuable information regarding the synthesis process by acting as an internal probe. A three-stage, one-dimensional crystallization mechanism is proposed: (i) an initial reaction between aluminum and phosphate units forming a primary amorphous phase, (ii) progressive condensation of linear Al-O-P chains forming a poorly ordered structure separated by template molecules up to ca. 155 degrees C, and (iii) rapid internal reorganization of the aluminophosphate network leading to crystallization of the AFI crystal structure.     

Highly selective asymmetric acetate aldol reactions of an N-acetyl thiazolidinethione reagent

[reaction: see text] A highly diastereoselective acetate aldol reaction that uses a tert-leucine-derived thiazolidinethione auxiliary and dichlorophenylborane has been developed. The reaction proceeds in excellent yields and with high diastereoselectivities (drs range from 9.5:1 to >100:1).     

Optimization of matrix-assisted laser desorption/ionization time-of-flight collision-induced dissociation using poly(ethylene glycol)

Details of the optimization of the collision-induced dissociation (CID) process, using a collision cell on a matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometer, are described using poly(ethylene glycol) 1000 (PEG 1000) as a model analyte. The effects of collision gas identity (helium, air, and argon), as well as collision gas pressure, on the resulting MS/MS data were investigated. With PEG 1000, helium was found to give the best results with respect to signal-to-noise (S/N) ratio. The optimum pressure for each gas was found to be in the range where the precursor ion signal was attenuated to approximately 30-50% for helium and 40-60% for argon. The effect of cation choice (Li, Na, and K) on the CID of PEG was also studied. CID spectra were produced for each, but PEG cationized with lithium was found to produce the spectra with the highest S/N ratio. The MALDI-TOF CID spectra that were generated for PEG were compared with the high-energy and low-energy MS/MS spectra obtained from a sector mass spectrometer and from a triple quadrupole mass spectrometer, respectively. The results observed for PEG confirm that CID on a MALDI-TOF mass spectrometer is a high-energy MS/MS technique.     

Synthesis of 2– and 4-amino-1,5-naphthyridines

The structure of the product obtained from the reaction of potassium amide in liquid ammonia on 1,5-naphthyridine has been identified as 4-amino-1,5-naphthyridine by comparison with a known sample. The 2-amino isomer was not detected in the mixture. The NMR spectra for 2-and 4-amino-1,5-naphthyridine along with the corresponding chloroisomers are described.     

Asymmetric synthesis of 4,4-disubstituted-2-imidazoli-dinones: potent NK1 antagonists

[structure: see text] A highly efficient and practical synthesis of 4,4-Disubstituted-2-Imidazolidinones utilizing a "self-reproduction of the center of chirality" strategy is described.