Scalable Hybrid Synthetic/Biocatalytic Route to Psilocybin

Psilocybin, the principal indole alkaloid of Psilocybe mushrooms, is currently undergoing clinical trials as a medication against treatment-resistant depression and major depressive disorder. The psilocybin supply for pharmaceutical purposes is met by synthetic chemistry. We replaced the problematic phosphorylation step during synthesis with the mushroom kinase PsiK. This enzyme was biochemically characterized and used to produce one gram of psilocybin from psilocin within 20 minutes. We also describe a pilot-scale protocol for recombinant PsiK that yielded 150 mg enzyme in active and soluble form. Our work consolidates the simplicity of tryptamine chemistry with the specificity and selectivity of enzymatic catalysis and helps provide access to an important drug at potentially reasonable cost.     

A new method of assessing the efficiency of second harmonic generation by small samples of organic crystals

The intensity of optical second harmonic generation was measured from pressed KCl disks containing low concentrations (1%) of non-linear optical (NLO) materials. Comparison of the signals at 532 nm, with the known second order NLO coefficients exhibited a monotonic relationship. An estimate was made of the effect of light scattering at 532 nm, on the results.     

Surface analysis in electrochemical studies

Surface analysis methods are becoming increasingly important in the understanding of electrochemical systems. They provide complimentary information to that provided by electrochemical studies.     

The phototoxicity of photodynamic therapy may be suppressed or enhanced by modulation of the cutaneous vasculature

In photodynamic therapy, the threshold for light induced toxicity depends on the drug concentration and the light dose. This study was aimed to show for vascular photosensitizers that the toxicity threshold on normal tissue may be predictably modified by modulation of the cutaneous vasculature. Albino rabbits were injected with 1.0 mg/kg of a vascular photosensitizer, benzoporphyrin derivative monoacid ring-A. The threshold light dose for toxicity to normal skin was determined at an absorption maximum of the drug (694 nm), 1 h after drug injection. The cutaneous vasculature was dilated by prior skin exposure to ultraviolet radiation or was constricted by iontophoretic application of epinephrine. Threshold toxicity was determined clinically and by assessing the effective concentration of hemoglobin in the skin by diffuse reflectance spectroscopy (DRS). Tissue samples that received threshold doses were investigated with light and electron microscopy. The toxicity threshold increased by 3.2+/-0.9 (mean+/-S.D.) following vasoconstriction and decreased by 3.6+/-0.8 following vasodilation, compared to control sites. Light and electron microscopy showed similar findings at threshold for both vasodilated and vasoconstricted sites. Therefore vascular modulation may be used to predictably enhance or suppress the level of phototoxicity of normal skin.     

Frequency shifting through cascaded second-order processes in a N-(4-nitrophenyl)- L-prolinol crystal

We exploit the high second-order susceptibility of the organic crystal N-(4-nitrophenyl)-L-prolinol to accomplish, through a cascaded second-order process, wavelength conversion of a signal pulse (from 1.16 to 1.14 microm) under the action of a pump pulse (at 1.15 microm). In a 2.8-mm-thick crystal, wavelength conversion with unit gain was obtained with a pump peak intensity as low as 9 MW/cm(2) . At low intensities, in the limit of negligible conversion where the cascading effect can be described through an effective third-order susceptibility, we derive |(x)((3))(eff) | approximately 2.4 x 10(-17) m(2)/V(2), which is ~10(2) larger than the nonresonant (x)((3)) of conjugated polymers or semiconductors.     

Cephalexin: a channel hydrate

The antibiotic cephalexin [systematic name: d ‐7‐(2‐amino‐2‐phenyl­acet­amido)‐3‐methyl‐8‐oxo‐5‐thia‐1‐aza­bi­cyclo­[4.2.0]oct‐2‐ene‐2‐carboxyl­ic acid] forms a range of isomorphic solvates, with the maximum hydration state of two water mol­ecules formed only at high relative humidities. The water content of the structure reported here (C₁₆H₁₇N₃O₄S·1.9H₂O) falls just short of this configuration, having three independent cephalexin mol­ecules, one of which is disordered, and 5.72 observed water mol­ecules in the asymmetric unit. The facile nature of the cephalexin solvation/desolvation process is found to be facilitated by a complex channel structure, which allows free movement of solvent in the crystallographic a and b directions.     

Comparison of embedded cluster models to study zeolite catalysis: Proton transfer reactions in acidic chabazite

A number of cluster models used to study the interaction of NH₃ and NH⁻₄ with the Bronsted sites of the acidic zeolite, chabazite, are assessed by comparison with the results from full periodic Hartree-Fock calculations. Corrections to bare cluster models to take account of the electrostatic environment due to the periodic zeolite are found to agree well with periodic calculations, and appear to be more successful than a more sophisticated embedding procedure. © 1997 by John Wiley & Sons, Inc.     

Biomedical Engineering and Cognitive Science as the Basis for Secondary Science Curriculum Development: A Three Year Study

This study reports on a multiyear effort to create and evaluate cognitive‐based curricular materials for secondary school science classrooms. A team of secondary teachers, educational researchers, and academic biomedical engineers developed a series of curriculum units that are based in biomedical engineering for secondary level students in physics and advanced biology classes. These units made use of an instructional design based upon recent cognitive science research called the Legacy Cycle. Over a 3‐year period, comparison of student knowledge on written questions related to central concepts in physics and/or biology generally favored students who had worked with the experimental materials over students in control classrooms. In addition, experimental students were better able to solve applications type problems, as well as unit‐specific near transfer problems.     

Rheology of a dilute suspension: analytical expression for the viscosity in the limit of low zeta-potentials

A modified theoretical model on the primary electroviscous effect, based upon the inclusion of the condition of that the ions within the Stern layer are allowed to move tangential to the surface of the particle, is proposed. Booth's analysis (Booth 1950a), valid for spherical particles at low zeta-potentials, is the start point, and the effect of a dynamic Stern layer is included. The analytic results are compared with full numerical computations and a good agreement is found for zeta-potentials less than 25 mV. Received: 15 June 2000 Accepted: 11 September 2000