ABSTRACTThe mechanism of how (S)-crizotinib or (R)-crizotinib selectively recognises MutT homolog 1 (MTH1) was investigated by molecular dynamics simulations and molecular mechanics/Poisson-Boltzmann surface area (MMPBSA) free energy calculations. Our studies find that (S)-crizotinib could cause much more conformation fluctuation on MTH1 protein than (R)-crizotinib. Compared with (R)-crizotinib, (S)-crizotinib, to a greater degree, inhibited the anti-correlated motion of the whole MTH1 protein, especially the binding site. The closure motion of the binding site was slightly blocked by (R)-crizotinib, which should be attributed to the steric hindrance of (R)-crizotinib on loop 1 and loop 3. The closure motion of the binding site was greatly promoted by (S)-crizotinib, which should be attributed to the hydrogen bond interaction of (S)-crizotinib on loop 1 and loop 3. The stabilised degree of (S)-crizotinib on the binding pocket in MTH1 was more than that of (R)-crizotinib. In the lowest energy point, the presence of (R)-crizotinib made the binding site of MTH1 slightly become smaller, while the presence of (S)-crizotinib made the binding site of MTH1 form a stable hydrogen bond. These supported the experimental finding that the activity of (S)-crizotinib is superior to the (R)-crizotinib activity (IC50 72 vs. 1375 nM). The free energy calculations also confirmed this point. This work could not only illuminate the mechanism of (S)-crizotinib or (R)-crizotinib selectively recognising MTH1, but also provide a guideline of the design of such chiral drugs. 相似文献
A molecular spring formed by a hydrophobic metal–organic framework Cu2(tebpz) (tebpz=3,3′,5,5′‐tetraethyl‐4,4′‐bipyrazolate) and water is presented. This nanoporous heterogeneous lyophobic system (HLS) has exceptional properties compared to numerous reported systems of such type in terms of stability, efficiency, and operating pressure. Mechanical and thermal energetic characteristics as well as stability of the system are discussed and compared in detail with those of other previously reported HLS. 相似文献
A series of unprecedented cationic copper(i)-iodide aggregates, (Cu4I2)2+, (Cu6I2)4+ and (Cu10I4)6+, are trapped in the in situ formation of anionic-tetrazolate-based coordination polymers, namely [Cu2(mu3-I)(mu5-Cpta)]n (1), [Cu5(mu4-I)(mu4-Mtta)3(CN)]n (2) and [Cu5(mu6-I)(mu2-I)(mu4-Mtta)3](n) (3) [Cpta = 5-(3-cyanophenyl)tetrazolate, Mtta = 5-methyltetrazolate], which exhibit structure-related green, cyan and blue luminescence, respectively. 相似文献
Two new limonoid-type triterpenoids, named 12-o-ethyl-l-deacetylnimbolinin B and 1-o-tigloyl-1-o-debenzoylohchinal, have been isolated from the fruit of Melia toosendan Sieb. et Zucc. Their structures were elucidated by spectral methods, including 2D-NMR spectra. 相似文献
This paper discusses the inverse scattering problem for one-dimensional Schrodinger operators related to the general Stark effect. We provide a general framework which can be applied both to the Stark-effect operator and the ordinary Schrodinger operator. 相似文献
Reported is a novel palladium(II)‐initiated Catellani‐type reaction that utilizes widely accessible aryl boronic acids as the substrates instead of aryl halides, thereby greatly expanding the existing scope of this powerful transformation. This borono‐Catellani reaction was promoted by cooperative catalysis between Pd(OAc)2 and the inexpensive 5‐norbornene‐2‐carbonitrile. Practicality is the striking feature of the reaction: it is run open to air at ambient temperature and no phosphine ligand is needed. This mild, chemoselective, and scalable protocol is compatible with a large range of readily available functionalized aryl boronic acids and bromides, as well as terminating olefins (50 examples, 39–97 % yields). Moreover, the orthogonal reactivity between the borono‐Catellani and classical Catellani reaction was demonstrated. This work is expected to open new avenues for developing novel Catellani‐type reactions. 相似文献
The development of a highly sensitive, selective, and efficient sensor for the determination and detection of Cr(III) ions remains a great challenge. Recently, some fluorescent chemosensors have been developed for the recognition of Cr(III) ions. But, the main drawbacks of the reported fluorescent chemosensors are the lack of selectivity and interference of anions and other trivalent cations. Herein, we designed and synthesized a novel thiazole-based fluorescent and colorimetric Schiff base chemosensor SB2 for the detection of Cr(III) ion by chemodosimetric approach. Using different analytical techniques including UV–vis, 13C-NMR, 1H-NMR, and FT-IR analysis the chemosensor SB2 was structurally characterized. The fully characterized chemosensor SB2 was used for the spectrofluorimetric and colorimetric detection of Cr(III) ions. Interestingly, chemosensor SB2 upon interaction with various metal cations including Ni2+, Na+, Cd2+, Ag+, Mn2+, K+, Zn2+, Cu2+, Hg2+, Co2+, Pb2+, Mg2+, Sn2+, Al3+ and Cr3+ displays highly selective and sensitive fluorescent (turn-on) and colorimetric (yellow to colorless) response toward Cr(III) ions. The fluorescence and UV–vis techniques confirmed the selective hydrolysis of azomethine group (-C?=?N-) of Schiff base chemosensor SB2 by Cr(III) ions. As a result, the fluorescence enhancement was observed that is corresponding to 2-hydroxy-1-nepthaldehyde (fluorophore). The chemosensor SB2 exhibits high interference performance towards Cr(III) ions over other metal cations in a wide pH range. Mover, the quite low detection limit was calculated to be 0.027 µg ml-1 (0.5 µM) (3σ/slop), lower than the maximum tolerable limits of Cr(III ions (10 µM) in drinking water permitted by the United States Environmental Protection Agency (EPA). These results show that chemosensor SB2 has great potential to detect selectively Cr(III) ions in the agricultural, environmental and biological analysis system.