Solvent as a Probe of Active Site Motion and Chemistry during the Hydrogen Tunnelling Reaction in Morphinone Reductase

The reductive half‐reaction of morphinone reductase involves a hydride transfer from enzyme‐bound β‐nicotinamide adenine dinucleotide (NADH) to a flavin mononucleotide (FMN). We have previously demonstrated that this step proceeds via a quantum mechanical tunnelling mechanism. Herein, we probe the effect of the solvent on the active site chemistry. The pK_a of the reduced FMN N1 is 7.4±0.7, based on the pH‐dependence of the FMN midpoint potential. We rule out that protonation of the reduced FMN N1 is coupled to the preceding H‐transfer as both the rate and temperature‐dependence of the reaction are insensitive to changes in solution pH above and below this pK_a. Further, the solvent kinetic isotope effect is ～1.0 and both the 1° and 2° KIEs are insensitive to solution pH. The effect of the solvent’s dielectric constant is investigated and the rate of H‐transfer is found to be unaffected by changes in the dielectric constant between ～60 and 80. We suggest that, while there is crystallographic evidence for some water in the active site, the putative promoting motion involved in the H‐tunnelling reaction is insensitive to such changes.     

Barrier Compression Enhances an Enzymatic Hydrogen‐Transfer Reaction

Putting the squeeze on : Hydrostatic pressure causes a shortening of the charge‐transfer bond in the binary complex of morphinone reductase and NADH₄ (see diagram). Molecular dynamics simulations suggest that pressure reduces the average reaction barrier width by restricting the conformational space available to the flavin mononucleotide and NADH within the active site. The apparent rate of catalysis increases with pressure.

     

Laminarisation and re-transition of a turbulent boundary layer subjected to favourable pressure gradient

 Experimental results are reported for the response of an initially turbulent boundary layer (Re _θ≈1700) to a favourable pressure gradient with a peak value of K≡(−υ/ρU ³ _E ) dp/dx equal to 4.4×10^-6. In the near-wall region of the boundary layer (y/δ<0.1) the turbulence intensity u′ scales roughly with the free-stream velocity U _E until close to the location where K is a maximum whereas in the outer region u′ remains essentially frozen. Once the pressure gradient is relaxed, the turbulence level increases throughout the boundary layer until K falls to zero when the near wall u′ levels show a significant decrease. The intermittency γ is the clearest indicator of a fundamental change in the turbulence structure: once K exceeds 3×10^-6, the value of γ in the immediate vicinity of the wall γ _s falls rapidly from unity, reaches zero at the location where K again falls below 3×10^-6 and then rises back to unity. Although γ is practically zero throughout the boundary layer in the vicinity of γ _s =0, the turbulence level remains high. The explanation for what appears to be a contradiction is that the turbulent frequencies are too low to induce turbulent mixing. The mean velocity profile changes shape abruptly where K exceeds 3×10^-6. Values for the skin friction coefficient, based upon hot-film measurements, peak at the same location as K and fall to a minimum close to the location where K drops back to zero. Received: 28 January 1998/Accepted: 8 April 1998     

7-Nitro-1-Oxaphenalene

3-Acetoxy-1-oxaphenalene⁴ (Ia) is conveniently prepared from naphthalene-1,8-carbalactone⁵ (IIa) by hydrolysis, condensation of the resulting hydroxy compound with chloroacetic acid and cyclisation of the resulting di-acid. Combined hydrolysis and reduction of (Ia) using alkaline potassium or sodium borohydride gives 2,3-dihydro-1-oxaphenalen-3-ol which may be converted into the 3-chloro-compound from which 1-oxaphenalene (Ib) is obtained by de-hydrochlorination.⁴     

Numerical analysis of gas-dynamic instabilities during the laser drilling process

The use of high-pressure gas jets in the laser-drilling process has significant influence on the melt ejection mechanism. These jets are highly unstable and this directly relates to the gas pressure and the geometry of the hole being drilled. The evolution of gas-dynamic instabilities during the laser-drilling process was investigated numerically. A minimum length nozzle (MLN) with a 300 μm throat diameter was modelled at various gas pressures, with the gas jet impinging on a range of simulated holes with different aspect ratios. The simulations predict the formation of surface pressure fluctuations that have a broad spectrum due to both the turbulent nature of the jet and the blunt shock oscillation on the surface. The surface pressure variations and the blunt shock oscillation govern the gas dynamic conditions inside the hole, which strongly influence the melt ejection phenomena during the laser-drilling process.     

What mathematicians know about the solutions of Schrodinger Coulomb Hamiltonian. Should chemists care?

An attempt is made to determine the relationship between the full Schrödinger Coulomb Hamiltonian and the clamped nuclei form that is usually the basis of electronic structure calculations, without treating identical nuclei as distinguishable. It is concluded that it is not at present possible to establish such a relationship in a mathematically secure way.     

Platonic instantons

The construction of Yang-Mills instantons with the symmetries of the platonic solids is described within the ADHM construction. As an example, the ADHM data is presented for an icosahedrally symmetric charge seventeen instanton with the structure of the truncated icosahedron. Presented at the International Colloquium “Integrable Systems and Quantum Symmetries”, Prague, 16–18 June 2005.