Probing the Binding of 4β-(Benzoyl-thioureido)-4-deoxypodophyllotoxin to Human Serum Albumin by Molecular Spectroscopy

Journal of Solution Chemistry - The binding interaction of 4β-(benzoyl-thioureido)-4-deoxypodophyllotoxin (HY-1) with human serum albumin (HSA) was investigated by fluorescence,...     

Electrochemical and Theoretical Investigations of the Role of the Appended Base on the Reduction of Protons by [Fe(2) (CO)(4) (κ(2) -PNP(R) )(μ-S(CH(2) )(3) S] (PNP(R) ={Ph(2) PCH(2) }(2) NR, R=Me, Ph)

The behavior of [Fe(2) (CO)(4) (κ(2) -PNP(R) )(μ-pdt)] (PNP(R) =(Ph(2) PCH(2) )(2) NR, R=Me (1), Ph (2); pdt=S(CH(2) )(3) S) in the presence of acids is investigated experimentally and theoretically (using density functional theory) in order to determine the mechanisms of the proton reduction steps supported by these complexes, and to assess the role of the PNP(R) appended base in these processes for different redox states of the metal centers. The nature of the R substituent of the nitrogen base does not substantially affect the course of the protonation of the neutral complex by CF(3) SO(3) H or CH(3) SO(3) H; the cation with a bridging hydride ligand, 1?μH(+) (R=Me) or 2?μH(+) (R=Ph) is obtained rapidly. Only 1?μH(+) can be protonated at the nitrogen atom of the PNP chelate by HBF(4) ?Et(2) O or CF(3) SO(3) H, which results in a positive shift of the proton reduction by approximately 0.15?V. The theoretical study demonstrates that in this process, dihydrogen can be released from a η(2) -H(2) species in the Fe(I) Fe(II) state. When R=Ph, the bridging hydride cation 2?μH(+) cannot be protonated at the amine function by HBF(4) ?Et(2) O or CF(3) SO(3) H, and protonation at the N atom of the one-electron reduced analogue is also less favored than that of a S atom of the partially de-coordinated dithiolate bridge. In this situation, proton reduction occurs at the potential of the bridging hydride cation, 2?μH(+) . The rate constants of the overall proton reduction processes are small for both complexes 1 and 2 (k(obs) ≈4-7?s(-1) ) because of the slow intramolecular proton migration and H(2) release steps identified by the theoretical study.     

Chemoenzymatic synthesis of (2S,3S,4S)-form, the physiologically active stereoisomer of dehydroxymethylepoxyquinomicin (DHMEQ), a potent inhibitor on NF-κB

A new route for (2S,3S,4S)-form, the physiologically active stereoisomer of dehydroxymethylepoxyquinomicin (DHMEQ), a potent NF-κB inhibitor, was established by chemoenzymatic approach. Elaboration on the asymmetric epoxidation of a p-benzoquinone monoketal with benzylcinchonidinium tert-butylhydroperoxide yielded an epoxyenone, in 79.8% ee and 57% yield in reproducible manner. By way of the transformation of this key intermediate to enantiomerically pure (2S,3S,4S)-DHMEQ, the contaminating undesired enantiomer could be effectively removed by applying Burkholderia cepacia lipase-catalyzed hydrolysis of diacylated precursor. The above integrated combination of chemical asymmetric synthesis and enzyme-catalyzed kinetic resolution enabled us to prepare active DHMEQ in a large-scale.     

Additive character of electron donation by methyl substituents within a complete series of polymethylated [1-(η6-Me9n)C6H(6-n))-closo-1,2,3-FeC2B9H11] complexes. Linear correlations of the NMR parameters and Fe(II/III) redox potentials with the number of arene methyls

A systematic method for the incorporation of the {(η(6)-Me(n)C(6)H(6-n))Fe} fragment into the dicarbollide cage was developed based on reactions between [(η(6)-Me(n)C(6)H(6-n))(2)Fe][PF(6)](2) salts (1) and Tl(2)[nido-7,8-C(2)B(9)H(11)]. These reactions proceed with elimination of one arene ligand to generate a complete series of the neutral [1-(η(6)-Me(n)C(6)H(6-n))-closo-1,2,3-FeC(2)B(9)H(11)] (2) complexes with n = 1-6 in yields ranging 15-70% depending on the arene. The structures of mesitylene and pentamethylbenzene complexes were established by X-ray diffraction analyses. All compounds were characterized by (11)B and (1)H NMR measurements, mass spectra, melting points and elemental analyses. Correlations between selected (1)H and (11)B NMR parameters and the Fe(II/III) redox potentials and the number of arene methyls for complexes 2 are linear. These facts establish direct evidence for a strictly additive character of electron donation by the methyl substituents to the arene ring and further to the Fe center and the second (dicarbollide) ligand.Correlations between the number of arene methyls (n) and selected (1)H and (11)B NMR parameters or the Fe(II/III) redox potentials for complexes [1-(η(6)-MenC(6)H(6-n))-closo-1,2,3-FeC(2)B(9)H(11)] are of strictly linear character.