Recognition of small polar molecules with an ionic crystal of alpha-Keggin-type polyoxometalate with a macrocation

The complexation of Keggin-type polyoxometalates [alpha-XW12O40]n- (X = P, Si, B, Co), macrocation [Cr3O(OOCH)6(H2O)3]+, and alkali-metal ions forms ionic crystals of Na2[Cr3O(OOCH)6(H2O)3][alpha-PW12O40].16H2O (1a), K3[Cr3O(OOCH)6(H2O)3][alpha-SiW12O40].16H2O (2a), Rb4[Cr3O(OOCH)6(H2O)3][alpha-BW12O40].16H2O (3a), and Cs5[Cr3O(OOCH)6(H2O)3][alpha-CoW12O40].7.5H2O (4a). The space volumes of the ionic crystals decrease in the order of 1a > 2a > 3a > 4a. The water of crystallization in 1a-3a is completely desorbed by evacuation at room temperature, while about 50% of the water of crystallization in 4a is desorbed. The respective 1a-4a after evacuation at room temperature are denoted by 1b-4b, which show the close packing of the constituent ions. The calculated cell volumes per formula decreased in the order of 1b > 2b > 3b > 4b, which would be related to the increase in n. Compound 1b sorbs various < or =C5 polar organic molecules such as 1-butanol, valeronitrile, and methyl propionate. Compound 2b sorbs ethanol, acetonitrile, and methyl formate. Compound 3b sorbs water and methanol, and 4b sorbs only water. Thus, the ionic crystals can discriminate < or =C5 polar organic molecules such as alcohols, nitriles, and esters by one methylene chain, and the decrease in n of [alpha-XW12O40]n- enables the sorption of molecules with the longer methylene chain. The nature of the sorption properties of 1b-4b can be explained by the lattice energy needed for the expansion of 1b-4b. The selective sorption properties of 1b-4b are successfully applied to the separation of mixtures of alcohols, nitriles, esters, and water.     

Antitumor enediyne chromoprotein C-1027: mechanistic investigation of the chromophore-mediated self-decomposition pathway

C-1027 is an extremely potent antitumor agent that causes double-stranded DNA cleavages. It is a unique small molecule-protein complex composed of a highly reactive enediyne chromophore, which upon binding reacts with its target molecule DNA through radical-mediated hydrogen abstraction and an apoprotein that encapsulates the chromophore serving as its carrier to reach DNA. Although C-1027 has favorable properties as an effective drug delivery system, it slowly self-decomposes due to the reactivity of the chromophore toward the apoprotein. Understanding how the C-1027 destroys itself may enable design of its analogues that overcome this limitation. In this paper, mechanistic insights into the self-reactivity of C-1027 that facilitates its own decomposition are described. We provide evidence that the formation of the Gly96 radical, which promotes the oxidative protein scission and the subsequent chromophore release, is the major pathway for the self-decomposition of C-1027. On the basis of the newly isolated products of the self-decomposition, we propose that the apoprotein effectively protects two different structural elements of the chromophore that are essential for its biological activity: the nine-membered enediyne moiety (necessary for DNA cleavage) and the benzoxazine moiety (necessary for DNA intercalation). Using an engineered apoprotein analogue kinetically more stable toward the chromophore radical, we show that enhanced overall properties can be achieved for the natural C-1027 with respect to stability and antitumor activities. The results present the first example of a rationally designed C-1027 analogue reported to display superior in vitro antitumor activity to the natural C-1027. Our findings may have implications for design of proteins that can stably encapsulate highly reactive small molecules.     

Hydration and dynamic behavior of poly(N-isopropylacrylamide)s in aqueous solution: a sharp phase transition at the lower critical solution temperature

The number of hydrated water molecules per poly(N-isopropylacrylamide) monomer unit in homogeneous aqueous solution was determined to be 11 exactly and anew below the lower critical solution temperature of 32 degrees C employing high-frequency dielectric relaxation techniques.     

Structures of new cucurbitane-type triterpenes and glycosides, karavilagenins and karavilosides, from the dried fruit of Momordica charantia L. in Sri Lanka

Three new cucurbitane-type triterpene called karavilagenins A, B, and C and five new cucurbitane-type triterpene glycosides called karavilosides I, II, III, IV, and V were isolated from the dried fruit of Sri Lanka Momordica charantia L. (Cucurbitaceae) together with two known cucurbitane-type triterpenes, 19(R)-methoxy-5beta,19-epoxycucurbita-6,23-dien-3beta,25-diol and 5,19-epoxycucurbita-6,23-diene-3,25-diol, and nine known cucurbitane-type triterpene glycosides, goyaglycosides-b, -c, and -d, and momordicosides F1, F2, G, I, K, and L. The structures of karavilagenins and karavilosides were elucidated on the basis of chemical and physicochemical evidence.     

A stable Schrock-type hafnium-silylene complex

The first stable hafnium-silylene complex, (eta-C5H4Et)2(PMe3)Hf=Si(SiMetBu2)2 (6) was obtained in the form of the phosphine adduct as red crystals by the coupling reaction of 1,1-dilithiosilane (1) with 0.9 equiv of (eta-C5H4Et)2HfCl2 in dry toluene at -50 degrees C, followed by treatment with an excess of PMe3 at -50 degrees C. In the 29Si NMR spectrum of 6, the signal from the silylene ligand is shifted greatly downfield at 295.4 ppm, with a JSiP coupling constant of 15.0 Hz. X-ray crystallographic analysis of 6 revealed that the Si-Hf bond length (2.6515(9) A) is about 5% shorter than typical Si-Hf single bonds, obviously indicating the double-bond character between the silicon and hafnium atoms. The compound 6 was found to be a Schrock-type silylene complex, a conclusion that was supported by the natural population analysis (NPA) charge distribution for the model complex, (eta-C5H4Et)2(PMe3)Hf=Si(SiMe3)2 (8), showing a negative charge on the silicon atom (-0.34).     

Novel 6-formylpterin derivatives: chemical synthesis and O2 to ROS conversion activities

6-Formylpterin (6FP) has been demonstrated to have strong neuroprotective effects against transient ischemia-reperfusion injury in gerbils. Also it has been shown that in rats, 6FP protected retinal neurons even when it was administered after the ischemic insult. Since there is a significant need for such a compound that effectively suppresses the events caused by the lack of oxygen supply, 6FP has attracted further investigation. Unfortunately, however, 6FP is hardly soluble in water at neutral pH and in organic solvents because of its self-assembling ability. Although a several mM solution of 6FP is available in alkaline water, it is unstable. In the present study, a novel chemical derivatization of 6FP has been developed which maintains the formyl group on the 6-position of 6FP, which is essential for the physiological activities of 6FP, and increases solubility in water and organic solvents. In the method, the 2- and 3-positions of 6FP were modified by a three component coupling reaction: 6FP was subjected to the reaction with acid chloride and N,N-dimethylformamide. The derivatives synthesized here, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridine-4-one 1, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-isobutyrylpteridine-4-one 2, and 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-o-toluoylpteridine-4-one 3, showed high solubility in water (1.0-5.6 mM) and organic solvents. The O(2) conversion property has also been determined for the derivative 1. Using an oxygen electrode, it has been found that O(2) is consumed in the presence of 1 and NADH at around pH 7.4 and that the rate of O(2) consumption is enhanced by UV-A irradiation. Electron paramagnetic resonance (EPR) analysis coupled with DMPO spin trapping has also revealed that in the presence of NADH, 1 converts O(2) to O(2)(-), which is further reduced to OH. By UV-A illumination in the analogous systems, (1)O(2) formation was observed. These results are similar to those reported previously for 6FP.     

Alternative methodology for the analysis of progesterone, testosterone, and epi-testosterone in bovine liver and veal muscle

Research has shown that traditional solvent extraction procedures used for the analysis of endogenous steroids often give inconsistent recoveries and results. However, a single-laboratory validation of a liquid chromatography/tandem mass specrometry method using 2 product ions per transition for progesterone, testosterone, and epi-testosterone in bovine liver and veal muscle showed accuracy and precision to within 23% at concentrations ranging from 0.5 to 2.0 microg/kg. Homogenized samples were pretreated with methanol to denature endogenous enzymes. Following removal of methanol, samples were treated overnight with Helix pomatia beta-glucuronidase to deconjugate glucuronide conjugates. Alkali digestion of the samples in KOH solutions was done under shaking at 37 degrees C for 30 min. The digestate was extracted with methyl tert-butyl ether, and the extracts were cleaned by partitioning between acetonitrile-hexane, followed by solid-phase extraction cleanup on silica cartridges. In bovine liver, average recoveries exceeded 54% for all analytes, and the within-run assay coefficients of variations were < 6 and 13% for high (2.0 microg/kg) and low (0.3 microg/kg) analyte concentrations, respectively. In veal muscle, average recoveries exceeded 60%, and the analysis of blind spikes gave accuracy estimates of over 85%, with coefficients of variation (CVs) < 15% for all analytes. The CVs for the multiple reaction monitoring ion ratios for all compounds were < 22% for all validation data. The method meets the requirements for confirmatory methods as outlined in 2002/657/EC. An analyst is capable of processing up to 20 samples within 5 days.     

Dynamical calculations of charge-transfer-to-solvent excited states of small I- (CH3CN)n clusters

Relaxation dynamics of photoexcited charge-transfer-to-solvent (CTTS) states for the I(-)(CH(3)CN)(n) (n = 2 and 3) clusters has been theoretically studied using electronic structure methods. First, we have calculated several lowest singlet and triplet potential energy surfaces using the multireference configuration interaction method. It was found that the character of the singlet CTTS excited-state potential surfaces is very similar to that of the triplet CTTS states. Due to a small singlet-triplet splitting, the lowest triplet potential energy surface was used as a good model to understand the dynamics of the photoexcited singlet CTTS states. We have carried out direct molecular dynamics simulations on the lowest triplet surface at the B3LYP level. When an I(-) anion is exteriorly solvated by CH(3)CN molecules, we found that the (CH(3)CN)(n)(-) anion cluster is effectively produced. In addition, when the I(-) anion is placed in the interior in I(-)(CH(3)CN)(n) clusters, photoexcitation gives an acetonitrile monomer anion plus neutral monomers. However, if the initial geometric configuration is distorted from the minimum structure, we also found that the (CH(3)CN)(2)(-) anion cluster, where an excess electron is internally trapped, is formed via I(-)(CH(3)CN)(2) + hnu --> I + (CH(3)CN)(2)(-) process.     

Room-temperature synthesis of gold nanoparticles and nanoplates using Shewanella algae cell extract

Biosynthesis of spherical gold nanoparticles and gold nanoplates was achieved at room temperature and pH 2.8 when cell extract from the metal-reducing bacterium Shewanella algae was used as both a reducing and shape-controlling agent. Cell extract, prepared by sonicating a suspension of S. algae cells, was capable of reducing 1 mol/m³ aqueous AuCl₄ ⁻ ions into elemental gold within 10 min when H₂ gas was provided as an electron donor. The time interval lapsed since the beginning of the bioreductive reaction was found to be an important factor in controlling the morphology of biogenic gold nanoparticles. After 1 h, there was a large population of well-dispersed, spherical gold nanoparticles with a mean size of 9.6 nm. Gold nanoplates with an edge length of 100 nm appeared after 6 h, and 60% of the total nanoparticle population was due to gold nanoplates with an edge length of 100–200 nm after 24 h. The yield of gold nanoplates prepared with S. algae extract was four times higher than that prepared with resting cells of S. algae. The resulting biogenic gold nanoparticle suspensions showed a large variation in color, ranging from pale pink to purple due to changes in nanoparticle morphology.