Paramagnet enhanced nuclear relaxation of H2 in organic solvents and in H2@C60

We have measured the bimolecular contribution (relaxivity) R1 (M(-1) s(-1)) to the spin-lattice relaxation rate for the protons of H2 and H2@C60 dissolved in organic solvents in the presence of paramagnet nitroxide radicals. It is found that the relaxation effect of the paramagnets is enhanced 5-fold in H2@C60 compared to H2 under the same conditions. 13C relaxivity in C60 induced by nitroxide has also been measured. The resulting value of R1 for 13C is substantially smaller relative to the 1H relaxation in H2@C60 than expected solely on the basis of the smaller magnetic moment of 13C. The observed values of R1 have been analyzed quantitatively using an outer-sphere model for bimolecular spin relaxation to extract an encounter distance, d, as the dependent variable. The resulting values of d for H2 and (13)C60 are similar to the sum of the van der Waals radii for the radical and the corresponding molecule. The value of d for (1)H2@C60 is substantially smaller than the corresponding van der Waals estimates, corresponding to larger than expected values of R1. A possible explanation for the enhanced relaxivity is a contribution from hyperfine coupling. Based on the results reported here, it seems that not only is the hydrogen molecule in H2@C60 not insulated from magnetic contact with the outside world but also the interaction with paramagnets is even stronger than expected based on distance alone.     

Structure-activity relationships of estrogen derivatives as aromatase inhibitors. Effects of heterocyclic substituents

Aromatase, which is responsible for the conversion of androgens to estrogens, is a potential therapeutic target for the selective lowering estrogen level in patients with estrogen-dependent breast cancer. We prepared and tested series of the pyridine- and other heterocyclic ring-containing derivatives of 2- and 4-aminoestrones, estrone, and estradiol, compounds 5, 10, 12 and 15. The isonicotinyl derivatives of 2- and 4-aminoestrone, compounds 5c and 10c, were fairly potent competitive inhibitors of aromatase (K(i), 2.1+/-0.14 and 1.53+/-0.08 microM for 5c and 10c, respectively) and other compounds did not show, to a significant extent, the aromatase inhibitory activity. This result suggests that the isonicotinyl-substituted derivatives 5c and 10c would be accessible to the active site of aromatase.     

The Photocatalytic Degradation of Imazapyr

Summary. The degradation of imazapyr, an imidazolinone herbicide, in aqueous solution has been investigated with TiO₂ slurry as photocatalyst at 30°C under UV radiation. The depletion of imazapyr concentration in an aqueous suspension followed 1^st order kinetic behavior. The influence of pH and the charge densities of imazapyr geometries were calculated at the semi-empirical AM1 level, and the effect of temperature was investigated. The addition of electron acceptors such as potassium persulfate and hydrogen peroxide showed that the rate constant doubled at least. At higher persulfate concentrations the herbicide degradation was more efficient in direct photolysis than TiO₂-photocatalysis. The degradation rate constant increased by 38% upon variation of the temperature between 20.0 and 50.0°C and displayed non-Arrhenius behavior.     

Asymmetric Total Synthesis of Cytotrienin A: Late-Stage Installation of C11 Side Chain onto the Macrolactam Scaffold

Cytotrienin A, an ansamycin-class antibiotic, exhibits potent apoptosis-inducing activity and has attracted much attention as a lead compound for anticancer drugs. Herein, we report a new asymmetric synthetic route to cytotrienin A, employing an unexplored approach involving the late-stage installation of a C11 side chain onto the macrolactam core. In this strategy, we utilized the redox properties of hydroquinone and installed a side chain on the sterically hindered C11 hydroxy group by the traceless Staudinger reaction. This study also demonstrated that the boron-Wittig/iterative Suzuki–Miyaura cross-coupling sequence was effective for the concise and selective construction of the (E,E,E)-conjugated triene moiety. The developed route opens new opportunities for the structure–activity relationship studies of the side chains of these ansamycin antibiotics and the preparation of other synthetic analogs and chemical probes for further biological studies.     

Genealized poly-Cauchy and poly-Benoulli numbes by using incomplete $${\vavec{}}$$-Stiling numbes

In this paper we introduce restricted r-Stirling numbers of the first kind. Together with restricted r-Stirling numbers of the second kind and the associated r-Stirling numbers of both kinds, by giving more arithmetical and combinatorial properties, we introduce a new generalization of incomplete poly-Cauchy numbers of both kinds and incomplete poly-Bernoulli numbers.     

Development of a Sensitive Bioluminogenic Probe for Imaging Highly Reactive Oxygen Species in Living Rats

A sensitive bioluminogenic probe for highly reactive oxygen species (hROS), SO₃H‐APL, was developed based on the concept of dual control of bioluminescence emission by means of bioluminescent enzyme‐induced electron transfer (BioLeT) and modulation of cell‐membrane permeability. This probe enables non‐invasive visualization of physiologically relevant amounts of hROS generated deep inside the body of living rats for the first time. It is expected to serve as a practical analytical tool for investigating a wide range of biological functions of hROS in vivo. The design concept should be applicable to other in vivo bioluminogenic probes.     

Heme Pocket Architecture in Human Serum Albumin: Regulation of O2 Binding Affinity of a Prosthetic Heme Group by Site-Directed Mutagenesis

Summary : We present the O₂ binding properties of recombinant human serum albumin (rHSA) mutants complexed with an iron(II) protoporphyrin IX as a prosthetic heme group. Iron(III) protoporphyrin IX (hemin) is bound within subdomain IB of HSA with weak axial coordination by Tyr-161. In order to confer O₂ binding capability to this naturally occurring hemoprotein: (i) a proximal histidine was introduced into position Ile-142; and (ii) the coordinated Tyr-161 was replaced with hydrophobic Leu using site-directed mutagenesis. It provided a recombinant HSA double-mutant [rHSA(I142H/Y161L) = rHSA(HL)]. The rHSA(HL)–heme formed a ferrous five-coordinate high-spin complex with axial ligation of His-142 under an Ar atmosphere. This artificial hemoprotein binds O₂ at room temperature. Laser flash photolysis experiments demonstrated that O₂ rebinidng to rHSA(HL)–heme displays monophasic kinetics, whereas the CO recombination process obeyed a double-exponential pattern. This might be attributable to the two different geometries of the axial imidazole coordination arising from the two orientations of the porphyrin plane in the heme pocket. The O₂ binding affinity of rHSA(HL)–heme was considerably lower than those of R-state hemoglobin (Hb) and myoglobin (Mb), principally because of the high O₂ dissociation rate constant. The third mutations have been introduced into the distal side of the heme (at position Leu-185 or Arg-186) to increase the O₂ binidng affinity. The rHSA(HL/L185N)–heme showed high O₂ binding affinity ( : 1 Torr), which is 18-fold greater than that of the original double mutant rHSA(HL)–heme and which is rather close to those of Hb (R-state) and Mb. Furthermore, replacement of polar Arg-186 with Leu or Phe adjusted the O₂ binding affinity ( ) to 10 Torr, which is almost equivalent to value for human red blood cells.     

Three-dimensional freezing of water in a copper foils porous layer around a coolant-carrying tube

Three-dimensional freezing of water around a coolant carrying horizontal tube placed in an adiabatic rectangular cavity partially including copper foils is investigated numerically and by experiment. Both, enhancement of freezing and a uniform freezing rate are achieved. The present numerical analysis predicts well the transient solid fraction found by experiments.