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Trifluoroacetamide is easily monoalkylated in a K2 CO3-organic solvent solid-liquid two-phase system affording in good to excellent yields N-alkyltrifluoroacetamides. Under the same conditions, the latter, in turn, react with alkylating agents giving N, N-dialkyltrifluoroacetamides in high yields. 相似文献
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Luciano Telesca Michele Lovallo Abuo El-Ela Amin Mohamed Mohamed ElGabry Sherif El-hady Kamal M. Abou Elenean Rafaat ElShafey Fat ElBary 《Physica A》2012
The interevent-time (IET) and interevent-distance (IED) series of seismic events occurred at Aswan area (Egypt) from 2004 to 2010 were investigated by means of the Fisher Information Measure and the Shannon entropy. The analysis was performed varying the depth and the magnitude thresholds. The results point out to an increase of level of organization and order with the decrease of magnitude threshold and the increase of depth threshold for the IET series, while the IED series are characterized by a level of uncertainty approximately constant with the threshold magnitude. The complexity measure, calculated as the product of the Fisher Information Measure and the Shannon entropy power, presents very similar pattern for both the types of seismic series, indicating an increasing complexity with the decrease of the threshold magnitude and the increase of the threshold depth. 相似文献
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Luca Mazzei Michele Cianci Stefano Benini Stefano Ciurli 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(52):12145-12158
Urease uses a cluster of two NiII ions to activate a water molecule for urea hydrolysis. The key to this unsurpassed enzyme is a change in the conformation of a flexible structural motif, the mobile flap, which must be able to move from an open to a closed conformation to stabilize the chelating interaction of urea with the NiII cluster. This conformational change brings the imidazole side chain functionality of a critical histidine residue, αHis323, in close proximity to the site that holds the transition state structure of the reaction, facilitating its evolution to the products. Herein, we describe the influence of the solution pH in modulating the conformation of the mobile flap. High-resolution crystal structures of urease inhibited in the presence of N-(n-butyl)phosphoric triamide (NBPTO) at pH 6.5 and pH 7.5 are described and compared to the analogous structure obtained at pH 7.0. The kinetics of urease in the absence and presence of NBPTO are investigated by a calorimetric assay in the pH 6.0–8.0 range. The results indicate that pH modulates the protonation state of αHis323, which was revealed to have pKa=6.6, and consequently the conformation of the mobile flap. Two additional residues (αAsp224 and αArg339) are shown to be key factors for the conformational change. The role of pH in modulating the catalysis of urea hydrolysis is clarified through the molecular and structural details of the interplay between protein conformation and solution acidity in the paradigmatic case of a metalloenzyme. 相似文献
69.
Synthesis and Biological Evaluation of RGD Peptidomimetic–Paclitaxel Conjugates Bearing Lysosomally Cleavable Linkers 下载免费PDF全文
Alberto Dal Corso Dr. Michele Caruso Dr. Laura Belvisi Dr. Daniela Arosio Prof. Dr. Umberto Piarulli Dr. Clara Albanese Dr. Fabio Gasparri Dr. Aurelio Marsiglio Dr. Francesco Sola Dr. Sonia Troiani Dr. Barbara Valsasina Dr. Luca Pignataro Dr. Daniele Donati Prof. Dr. Cesare Gennari 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(18):6921-6929
Two small‐molecule–drug conjugates (SMDCs, 6 and 7 ) featuring lysosomally cleavable linkers (namely the Val–Ala and Phe–Lys peptide sequences) were synthesized by conjugation of the αvβ3‐integrin ligand cyclo[DKP–RGD]‐CH2NH2 ( 2 ) to the anticancer drug paclitaxel (PTX). A third cyclo[DKP–RGD]–PTX conjugate with a nonpeptide “uncleavable” linker ( 8 ) was also synthesized to be tested as a negative control. These three SMDCs were able to inhibit biotinylated vitronectin binding to the purified αVβ3‐integrin receptor at nanomolar concentrations and showed good stability at pH 7.4 and pH 5.5. Cleavage of the two peptide linkers was observed in the presence of lysosomal enzymes, whereas conjugate 8 , which possesses a nonpeptide “uncleavable” linker, remained intact under these conditions. The antiproliferative activities of the conjugates were evaluated against two isogenic cell lines expressing the integrin receptor at different levels: the acute lymphoblastic leukemia cell line CCRF‐CEM (αVβ3?) and its subclone CCRF‐CEM αVβ3 (αVβ3+). Fairly effective integrin targeting was displayed by the cyclo[DKP–RGD]–Val–Ala–PTX conjugate ( 6 ), which was found to differentially inhibit proliferation in antigen‐positive CCRF‐CEM αVβ3 versus antigen‐negative isogenic CCRF‐CEM cells. The total lack of activity displayed by the “uncleavable” cyclo[DKP–RGD]–PTX conjugate ( 8 ) clearly demonstrates the importance of the peptide linker for achieving the selective release of the cytotoxic payload. 相似文献
70.
Michele Zilletti Stephen J. Elliott Emiliano Rustighi 《Journal of sound and vibration》2012,331(18):4093-4100
The tuning of a dynamic vibration absorber is considered such that either the kinetic energy of the host structure is minimised or the power dissipation within the absorber is maximised. If the host structure is approximated as a damped single degree of freedom, the optimal values for the ratio of the absorber's natural frequency to the host structure and the optimal damping ratio of the absorber are shown to be the same whether the kinetic energy of the host structure is minimised or the power dissipation of the absorber is maximised. It is also demonstrated that the total power input into the system does not depend on the two parameters but only on the host structure's mass. 相似文献