Cationic Mn(III) N-alkylpyridylporphyrins (MnPs) are potent SOD mimics and peroxynitrite scavengers and diminish oxidative stress in a variety of animal models of central nervous system (CNS) injuries, cancer, radiation, diabetes, etc. Recently, properties other than antioxidant potency, such as lipophilicity, size, shape, and bulkiness, which influence the bioavailability and the toxicity of MnPs, have been addressed as they affect their in vivo efficacy and therapeutic utility. Porphyrin bearing longer alkyl substituents at pyridyl ring, MnTnHex-2-PyP(5+), is more lipophilic, thus more efficacious in vivo, particularly in CNS injuries, than the shorter alkyl-chained analog, MnTE-2-PyP(5+). Its enhanced lipophilicity allows it to accumulate in mitochondria (relative to cytosol) and to cross the blood-brain barrier to a much higher extent than MnTE-2-PyP(5+). Mn(III) N-alkylpyridylporphyrins of longer alkyl chains, however, bear micellar character, and when used at higher levels, become toxic. Recently we showed that meta isomers are ~10-fold more lipophilic than ortho species, which enhances their cellular accumulation, and thus reportedly compensates for their somewhat inferior SOD-like activity. Herein, we modified the alkyl chains of the lipophilic meta compound, MnTnHex-3-PyP(5+) via introduction of a methoxy group, to diminish its toxicity (and/or enhance its efficacy), while maintaining high SOD-like activity and lipophilicity. We compared the lipophilic Mn(III) meso-tetrakis(N-(6'-methoxyhexyl)pyridinium-3-yl)porphyrin, MnTMOHex-3-PyP(5+), to a hydrophilic Mn(III) meso-tetrakis(N-(2'-methoxyethyl)pyridinium-3-yl)porphyrin, MnTMOE-3-PyP(5+). The compounds were characterized by uv-vis spectroscopy, mass spectrometry, elemental analysis, electrochemistry, and ability to dismute O(2)˙(-). Also, the lipophilicity was characterized by thin-layer chromatographic retention factor, R(f). The SOD-like activities and metal-centered reduction potentials for the Mn(III)P/Mn(II)P redox couple were similar-to-identical to those of N-alkylpyridyl analogs: log k(cat) = 6.78, and E(1/2) = +68 mV vs. NHE (MnTMOHex-3-PyP(5+)), and log k(cat) = 6.72, and E(1/2) = +64 mV vs. NHE (MnTMOE-3-PyP(5+)). The compounds were tested in a superoxide-specific in vivo model: aerobic growth of SOD-deficient E. coli, JI132. Both MnTMOHex-3-PyP(5+) and MnTMOE-3-PyP(5+) were more efficacious than their alkyl analogs. MnTMOE-3-PyP(5+) is further significantly more efficacious than the most explored compound in vivo, MnTE-2-PyP(5+). Such a beneficial effect of MnTMOE-3-PyP(5+) on diminished toxicity, improved efficacy and transport across the cell wall may originate from the favorable interplay of the size, length of pyridyl substituents, rotational flexibility (the ortho isomer, MnTE-2-PyP(5+), is more rigid, while MnTMOE-3-PyP(5+) is a more flexible meta isomer), bulkiness and presence of oxygen. 相似文献
We give a separable Brown-Douglas-Fillmore theorem. Let be a separable amenable -algebra which satisfies the approximate UCT, be a unital separable amenable purely infinite simple -algebra and be two monomorphisms. We show that and are approximately unitarily equivalent if and only if We prove that, for any 0$"> and any finite subset , there exist 0$"> and a finite subset satisfying the following: for any amenable purely infinite simple -algebra and for any contractive positive linear map such that
for all there exists a homomorphism such that
provided, in addition, that are finitely generated. We also show that every separable amenable simple -algebra with finitely generated -theory which is in the so-called bootstrap class is weakly stable with respect to the class of amenable purely infinite simple -algebras. As an application, related to perturbations in the rotation -algebras studied by U. Haagerup and M. Rørdam, we show that for any irrational number and any 0$"> there is 0$"> such that in any unital amenable purely infinite simple -algebra if
for a pair of unitaries, then there exists a pair of unitaries and in such that
We prove that a crossed product algebra arising from a minimal dynamical system on the product of the Cantor set and the circle has real rank zero if and only if the set of invariant measures of the system come from the associated Cantor minimal system. In the case that cocycles take values in the rotation group, it is also shown that this condition implies tracial rank zero, and in particular, the crossed product algebra is isomorphic to a unital simple AT-algebra of real rank zero. Under the same assumption, we show that two systems are approximately K-conjugate if and only if there exists a sequence of isomorphisms between two associated crossed products which approximately maps 相似文献
A new stabilized finite element method which is different from Hughes and Franco's (1988) is presented for the Reissner-Mindlin plate model. The least square mesh-dependent residual form of the shear constitute equation is added to the Partial Projection scheme to enhance the stability. Using piecewise polynomials of order k≥1 for the rotations, of order k+1 for the displacement and of order k-1 for the shear, the kth order error-estimates are obtained. Besides, our computing scheme can be also applied to some lower order elements. All error-estimates are obtained independent of the plate thickness, and the stability parameter is an arbitrary positive constant. 相似文献
Inspired by a paper of S. Popa and the classification theory of nuclear -algebras, we introduce a class of -algebras which we call tracially approximately finite dimensional (TAF). A TAF -algebra is not an AF-algebra in general, but a ``large' part of it can be approximated by finite dimensional subalgebras. We show that if a unital simple -algebra is TAF then it is quasidiagonal, and has real rank zero, stable rank one and weakly unperforated -group. All nuclear simple -algebras of real rank zero, stable rank one, with weakly unperforated -group classified so far by their -theoretical data are TAF. We provide examples of nonnuclear simple TAF -algebras. A sufficient condition for unital nuclear separable quasidiagonal -algebras to be TAF is also given. The main results include a characterization of simple rational AF-algebras. We show that a separable nuclear simple TAF -algebra satisfying the Universal Coefficient Theorem and having and is isomorphic to a simple AF-algebra with the same -theory.
A new complex [Ag4-S-mbo)4(dppp)4](1) is obtained from the reaction of AgBF4 and Hmbo(2-mercaptobenzoxazole) with the participation of dppp(bis(diphenylphosphino) propane). Single crystal X-ray diffraction analysis shows that it is discrete neutral molecule and composed of two asymmetrical moieties. Four Ag atoms in each molecule are completely coplanar and of similar environment. The ligands Hmbo and dppp in complex 1 bridge two Ag atoms through "μ2-S-mbo" and P atoms in two ends, respectively. The possible mechanism of the reaction is provided, and the sequence of adding materials and the length of backbone (CH2)n in diphosphine play an important role in the results of the reactions. 相似文献
Let X be a connected finite CW complex. We show that, given a positive homomorphism Hom(K*(C(X)), K*(A)) with [1C(X)][1A], where A is a unital separable simple C*-algebra with real rank zero, stable rank one and weakly unperforated K0(A), there exists a homomorphism h: C(X)A such that h induces . We also prove a structure result for unital separable simple C*-algebras A with real rank zero, stable rank one and weakly unperforated K0(A), namely, there exists a simple AH-algebra of real rank zero contained in A which determines the K-theory of A. 相似文献
We show that every separable nuclear residually finite dimensional -algebras satisfying the Universal Coefficient Theorem can be embedded into a unital separable simple AF-algebra.