Reaction of N,N-Dimethyltryptamine with Dichloromethane Under Common Experimental Conditions.

A large number of clinically used drugs and experimental pharmaceuticals possess the N,N-dimethyltryptamine (DMT) structural core. Previous reports have described the reaction of this motif with dichloromethane (DCM), a common laboratory solvent used during extraction and purification, leading to the formation of an undesired quaternary ammonium salt byproduct. However, the kinetics of this reaction under various conditions have not been thoroughly described. Here, we report a series of experiments designed to simulate the exposure of DMT to DCM that would take place during extraction from plant material, biphasic aqueous work-up, or column chromatography purification. We find that the quaternary ammonium salt byproduct forms at an exceedingly slow rate, only accumulates to a significant extent upon prolonged exposure of DMT to DCM, and is readily extracted into water. Our results suggest that DMT can be exposed to DCM under conditions where contact times are limited (<30 min) with minimal risk of degradation and that this byproduct is not observed following aqueous extraction. However, alternative solvents should be considered when the experimental conditions require longer contact times. Our work has important implications for preparing a wide-range of pharmaceuticals bearing the DMT structural motif in high yields and purities

Integrable Lattice Models for Conjugate An(1)A^{(1)}_n

A new class of $A^{(1)}_n$ integrable lattice models is presented. These are interaction-round-a-face models based on fundamental nimrep graphs associated with the $A^{(1)}_n$ conjugate modular invariants, there being a model for each value of the rank and level. The Boltzmann weights are parameterized by elliptic theta functions and satisfy the Yang-Baxter equation for any fixed value of the elliptic nome q. At q=0, the models provide representations of the Hecke algebra and are expected to lead in the continuum limit to coset conformal field theories related to the $A^{(1)}_n$ conjugate modular invariants.Comment: 18 pages. v2: minor changes, such as page 11 footnot

Analytic continuation of Wolynes theory into the Marcus inverted regime

The Wolynes theory of electronically nonadiabatic reaction rates [P. G. Wolynes, J. Chem. Phys. 87, 6559 (1987)] is based on a saddle point approximation to the time integral of a reactive flux autocorrelation function in the nonadiabatic (golden rule) limit. The dominant saddle point is on the imaginary time axis at $t_{\rm sp}=i\lambda_{\rm sp}\hbar$, and provided $\lambda_{\rm sp}$ lies in the range $-\beta/2\le\lambda_{\rm sp}\le\beta/2$, it is straightforward to evaluate the rate constant using information obtained from an imaginary time path integral calculation. However, if $\lambda_{\rm sp}$ lies outside this range, as it does in the Marcus inverted regime, the path integral diverges. This has led to claims in the literature that Wolynes theory cannot describe the correct behaviour in the inverted regime. Here we show how the imaginary time correlation function obtained from a path integral calculation can be analytically continued to $\lambda_{\rm sp}<-\beta/2$, and the continuation used to evaluate the rate in the inverted regime. Comparisons with exact golden rule results for a spin-boson model and a more demanding (asymmetric and anharmonic) model of electronic predissociation show that the theory it is just as accurate in the inverted regime as it is in the normal regime.Comment: 9 pages, 8 figure

Spotted Seals, Phoca largha, in Alaska

The worldwide literature on management of spotted seals, Phoca largha, was reviewed and updated, and aerial surveys weref lown in 1992 and 1993 to determine the species' distribution and abundance in U.S. waters. In April, spotted seals were found only in the Bering Sea ice front. In June, they were seen along deteriorating ice floes and fast ice in Norton Sound. Surveys along most of Alaska's western coast in August and September found over 2,500 spotted seals in Kuskokwim Bay and concentrations of 100-400 seals around Nunivak Island, Scammon Bay, Golovnin Bay/Norton Sound, Cape Espenberg/Kotzebue Sound, and Kasegaluk Lagoon. All of these sites have been used by spotted seals in the past. The sum of the highest counts, irrespective of year, was 3,570 seals (CV =0.06). This is not an abundance estimate for all spotted seals in the Bering Sea, because it does not account for animals in the water, and we did not survey the Asian coast and some islands. Also, spotted seals and harbor seals, Phoca vitulina, are too similar in appearance to be identified accurately from the air, so our results probably include a mix of these species where their ranges overlap

Evolution of malaria virulence in cross-generation transmission through selective immune pressure

Theoretical arguments and some mathematical models of host-parasite coevolution (e.g. [1- 6]) suggest host immunity as the driving source for the evolution of parasite virulence. Imperfect vaccines in particular, can play the role and recent work [7] sets to test these ideas experimentally, using the mouse malaria model, Plasmodium chabaudi. To this end the authors evolve parasite lines in immunized and nonimmunized (&#x201c;na&#xef;ve&#x201d;) mice using serial passage of infected blood samples. They find parasite lines evolved in immunized mice become more virulent than those evolved in naive mice. Furthermore, this feature persisted even when the evolved strains were transmitted through mosquitoes. &#xd;&#xa;Here we develop a mathematical model of parasite dynamics that qualitatively reproduces the experimental results of [7]. Our model accounts for the basic in-host processes: (i) production and depletion of red blood cells (RBC); (ii) immune-modulated parasite growth/ replication, (iii) immune stimulation and clearing of parasite. Besides we introduce multiple parasite strains with variable levels of virulence, and allow random mutations during replication process. The virulence is represented by a single parameter &#x2013; immune stimulation threshold. So more virulent strains have higher &#x201c;tolerance levels&#x201d;, hence increased RBC depletion (anemia). &#xd;&#xa;Numeric simulations with our model exhibit, as in [7] the overall evolution of virulence in serial passage of parasite strains, and its enhancement through partial (imperfect) immunization