Raman study of SO2 at high pressure: aggregation,phase transformations,and photochemistry

We report Raman measurements made on SO₂ in a diamond cell up to 75 kbar showing two new phases, solid II and solid III, which differ from known, zero-pressure solid I. Spectra indicate that SO₂ molecules aggregate in solid III to possibly form a cyclical trimer; solid III is shown to be photochemically active to blue radiation.     

Solid-state NMR study of intercalated species in poly(epsilon-caprolactone)/clay nanocomposites

The structure and dynamics of surfactant and polymer chains in intercalated poly(epsilon-caprolactone)/clay nanocomposites are characterized by (31)P magic-angle spinning (MAS) and (13)C cross-polarization MAS NMR techniques. To obtain hybrid materials with the low polymer content required for this study, in situ intercalative polymerization was performed by adapting a published procedure. After nanocomposite formation, the chain motion of the surfactant is enhanced in the saponite-based materials but reduced in the Laponite ones. Compared to the starting clay, the trans conformer population of the surfactant hydrocarbon chain in the nanocomposite decreases for the saponite systems. Mobility of the polymer chain is higher in the nanocomposites than in the bulk phase. The charge of the modified saponite does not significantly influence chain mobility in the nanocomposites.     

On the role of the conserved aspartate in the hydrolysis of the phosphocysteine intermediate of the low molecular weight tyrosine phosphatase

The usual rate-determining step in the catalytic mechanism of the low molecular weight tyrosine phosphatases involves the hydrolysis of a phosphocysteine intermediate. To explain this hydrolysis, general base-catalyzed attack of water by the anion of a conserved aspartic acid has sometimes been invoked. However, experimental measurements of solvent deuterium kinetic isotope effects for this enzyme do not reveal a rate-limiting proton transfer accompanying dephosphorylation. Moreover, base activation of water is difficult to reconcile with the known gas-phase proton affinities and solution phase pK(a)'s of aspartic acid and water. Alternatively, hydrolysis could proceed by a direct nucleophilic attack by a water molecule. To understand the hydrolysis mechanism, we have used high-level density functional methods of quantum chemistry combined with continuum electrostatics models of the protein and the solvent. Our calculations do not support a catalytic activation of water by the aspartate. Instead, they indicate that the water oxygen directly attacks the phosphorus, with the aspartate residue acting as a H-bond acceptor. In the transition state, the water protons are still bound to the oxygen. Beyond the transition state, the barrier to proton transfer to the base is greatly diminished; the aspartate can abstract a proton only after the transition state, a result consistent with experimental solvent isotope effects for this enzyme and with established precedents for phosphomonoester hydrolysis.     

Hetero Diels-Alder reactions of nitrosoamidines: an efficient method for the synthesis of functionalized guanidines

Hetero Diels-Alder reactions of transient nitrosoamidines are reported. Transient nitrosoamidines are formed by oxidation of protected N-hydroxylguanidines and are trapped in situ by 1,3-dienes to give [4 + 2] cycloadducts in good yields and regioselectivity. The resultant cycloadducts are versatile intermediates for the formation of functionalized guanidines. [reaction: see text]     

Therapeutic potential of phosphoinositide 3-kinase inhibitors

At least one Holy Grail for many academic researchers and pharmaceutical research divisions alike has been to identify therapeutically useful selective PI3K inhibitors. There are several different but closely related PI3Ks which are thought to have distinct biological roles. Until now, however, researchers have been frustrated by poor selectivity of the available pharmacological inhibitors, which are unable to distinguish the different isoforms of PI3K adequately. Fortunately, recently published work gives cause for optimism; there are now several patent specifications published that describe new PI3K inhibitors, including some that are more selective for the delta isoform of PI3K. Given the involvement of PI3Ks in a plethora of biological settings, such isoform-selective inhibitors may have immense potential use for the treatment of patients with inflammatory and autoimmune disorders as well as cancer and cardiovascular diseases.     

Synthetic models for the cysteinate-ligated non-heme iron enzyme superoxide reductase: observation and structural characterization by XAS of an Fe(III)-OOH intermediate

Superoxide reductases (SORs) belong to a new class of metalloenzymes that degrade superoxide by reducing it to hydrogen peroxide. These enzymes contain a catalytic iron site that cycles between the Fe(II) and Fe(III) states during catalysis. A key step in the reduction of superoxide has been suggested to involve HO(2) binding to Fe(II), followed by innersphere electron transfer to afford an Fe(III)-OO(H) intermediate. In this paper, the mechanism of the superoxide-induced oxidation of a synthetic ferrous SOR model ([Fe(II)(S(Me2)N(4)(tren))](+) (1)) to afford [Fe(III)(S(Me2)N(4)(tren)(solv))](2+) (2-solv) is reported. The XANES spectrum shows that 1 remains five-coordinate in methanolic solution. Upon reaction of 1 with KO(2) in MeOH at -90 degrees C, an intermediate (3) is formed, which is characterized by a LMCT band centered at 452(2780) nm, and a low-spin state (S = 1/2), based on its axial EPR spectrum (g(perpendicular) = 2.14; g(parallel) = 1.97). Hydrogen peroxide is detected in this reaction, using both (1)H NMR spectroscopy and a catalase assay. Intermediate 3 is photolabile, so, in lieu of a Raman spectrum, IR was used to obtain vibrational data for 3. At low temperatures, a nu(O-O) Fermi doublet is observed in the IR at 788(2) and 781(2) cm(-)(1), which collapses into a single peak at 784 cm(-1) upon the addition of D(2)O. This vibrational peak diminishes in intensity over time and essentially disappears after 140 s. When 3 is generated using an (18)O-labeled isotopic mixture of K(18)O(2)/K(16)O(2) (23.28%), the vibration centered at 784 cm(-1) shifts to 753 cm(-1). This new vibrational peak is close to that predicted (740 cm(-1)) for a diatomic (18)O-(18)O stretch. In addition, a nu(O-O) vibrational peak assigned to free hydrogen peroxide is also observed (nu(O-O) = 854 cm(-1)) throughout the course of the reaction between Fe(II)-1 and superoxide and is strongest after 100 s. XAS studies indicate that 3 possesses one sulfur scatterer at 2.33(2) A and four nitrogen scatterers at 2.01(1) A. Addition of two Fe-O shells, each containing one oxygen, one at 1.86(3) A and one at 2.78(3) A, improved the EXAFS fits, suggesting that 3 is an end-on peroxo or hydroperoxo complex, [Fe(III)(S(Me2)N(4)(tren))(OO(H))](+). Upon warming above -50 degrees C, 3 is converted to 2-MeOH. In methanol and methanol:THF (THF = tetrahydrofuran) solvent mixtures, 2-MeOH is characterized by a LMCT band at lambda(max) = 511(1765) nm, an intermediate spin-state (S = 3/2), and, on the basis of EXAFS, a relatively short Fe-O bond (assigned to a coordinated methanol or methoxide) at 1.94(10) A. Kinetic measurements in 9:1 THF:MeOH at 25 degrees C indicate that 3 is formed near the diffusion limit upon addition of HO(2) to 1 and converts to 2-MeOH at a rate of 65(1) s(-1), which is consistent with kinetic studies involving superoxide oxidation of the SOR iron site.     

Accelerating water exchange for GdIII chelates by steric compression around the water binding site

The water exchange process was accelerated for nine-coordinate, monohydrated macrocyclic GdIII complexes by inducing steric compression around the water binding site; the increased steric crowding was achieved by replacing an ethylene bridge of DOTA4- by a propylene bridge; in addition to the optimal water exchange rate, the stability of [Gd(TRITA)(H2O)]- is sufficiently high to ensure safe medical use which makes it a potential synthon for the development of high relaxivity, macromolecular MRI contrast agents.     

Stereoselective 1,2-cis glycosylation of 2-O-allyl protected thioglycosides

The technique of intramolecular aglycon delivery (IAD), whereby a glycosyl acceptor is temporarily appended to a hydroxyl group of a glycosyl donor is an attractive method that can allow the synthesis of 1,2-cis glycosides in an entirely stereoselective fashion. 2-O-Allyl protected thioglycoside donors are excellent substrates for IAD, and may be glycosylated stereoselectively through a three-step reaction sequence. This sequence consists of quantitative yielding allyl bond isomerisation, to produce vinyl ethers that can then undergo N-iodosuccinimide mediated tethering of the desired glycosyl acceptor, and subsequent intramolecular glycosylation, to yield either alpha-glucosides or beta-mannosides accordingly. Although attempted one-pot tethering and glycosylation is hampered by competitive intermolecular reaction with excess glycosyl acceptor, this problem can be simply overcome by the use of excess glycosyl donor. Allyl mediated IAD is a widely applicable practical alternative to other IAD approaches for the synthesis of beta-mannosides, that is equally applicable for alpha-gluco linkages. It is advantageous in terms of both simplicity of application and yield, and in addition has no requirement for cyclic 4,6-protection of the glycosyl donor.     

Termolecular ion-molecule reactions in Titan’s atmosphere. II: The structure of the association adducts of HCNH+ with C2H2 and C2H4

The ion-molecule reactivity of the products formed in the association reactions of HCNH+ with C2H2 (C3H4N+) and C2H4 (C3H6N+) has been investigated to provide information on the structures of the adducts thus formed. The C3H4N+ and C3H6N+ adducts were formed in the reaction flow tube of a flowing afterglow sourced-selected ion flow tube (FA-SIFT) and their reactivity with a neutral molecular "probe" examined. The reactivity of possible known structural isomers for the C3H4N+ and C3H6N+ ions was investigated in both the FA-SIFT and an ion cyclotron resonance spectrometer (ICR). Ab initio investigations of the potential energy surfaces for both structures at the G2(MP2) level have also been performed and structures corresponding to local minima on both surfaces have been identified and evaluated. The results of these experimental and theoretical studies show that at room temperature, the C3H4N+ adduct ion contains two isomers; a less reactive one that is likely to be a four-membered cyclic covalent isomer (approximately 70%) and a faster reacting component that is probably an electrostatic complex (approximately 30%). The C3H6N+ adduct ion formed from HCNH+ + C2H4 at room temperature is a single isomer that is likely to be the four-membered covalently bound cyclic CH2CH2CHNH+ species.     

CYCLIC VOLTAMMETRY MEASUREMENTS OF THE PHOTOELECTROGENIC REACTIONS OF THYLAKOID MEMBRANES

Abstract— In this paper, the technique of cyclic voltammetry has been used in a photoelectrochemical cell in order to follow the redox species formed in solution by the photo-induced electron transfer between the thylakoids and various acceptors and donors. The photoelectrochemical behavior of artificial electron acceptors (such as 2,5-dichlorobenzoquinone and methylviologen) and donors (such as sym -diphenylcarbazide and durohydroquinone) specific for either Photosystem I or Photosystem II has been investigated. The influence of inhibiting agents (such as 3-(3,4-dichlorophenyl)-1,1-dimethylurea and Tris) on the cell photoresponse has also been characterized, together with the capability of donors to restore the photocurrent. Evidence for H₂O₂ formation by way of a Mehler-type reaction has been provided and an electrochemical model of its coupled photochemical and electrochemical reactions in solution is reported.