Systematics melting behavior

C.B. Aakeroy, S. Forbes, J. Desper, Using cocrystals to systematically modulate aqueous solubility and melting behavior of an anticancer drug, J. Am. Chem. Soc. 131 (2009) 17048-17049. 

In conclusion, the selected examples of this chapter clearly demonstrate that it is possible with the discussed structural mod-ifiations to modify in a systematic manner the melting behavior over a wide temperature range, the degree of crystallization from highly crystalline to amorphous, and the so-... 

The phenomenon of thermotropic liquid crystallinity has been known at least since 1888. Since the early observations by Reinitzer and Lehmann of unusual melting behavior in certain organic compounds, mesogenic compounds have been both actively sought and incidentally discovered. Several relatively recent discoveries have shown the technological utility of organic mesophases. Substantial impetus has thus been provided for the systematic investigation of the relationships between molecular structure and liquid crystallinity. 

There is the raw stuff potentially available to answer this question. There are a couple of compounds known with the sulfur in the 4-position, which is the location of the oxygen atom in psilocybin. The 4-thio analogues have been synthesized from 4-methylthio-indole, via the oxalyl chloride method and reaction with the appropriate amine. With dimethylamine, the indoleglyoxylamide was made in a 43% yield and had a mp 163-164 °C. With diisopropylamine, the amide was made in a 27% yield and had a mp 190-192 °C. The final amines were prepared by the reduction of these amides with LAH in THF. N,N-Dimethyl-4-thiotryptamine (4-MeS-DMT) was obtained in a 68% yield and melted at 108-110 °C N,N-diisopropyl-4-methylthiotryptamine (4-MeS-DIPT) was obtained in a 61% yield and melted at 92-94 °C. In animal studies of behavioral disruption with these three compounds, there was systematic drop of potency in going from the 5-MeS-DMT to 4-MeS-DMT to 4-MeS-DIPT. 

We note here that systematic studies of the melting transition of dry or nearly dry phospholipids bilayers (e.g., vesicles) have been scarce. While there is an abundant experimental and theoretical literature concerning the structure and properties of bilayers in water, less is known about their behavior when water is removed. We have therefore initiated a systematic experimental study of the gel-liquid crystal transition of pure DPPC and DPPC-cholesterol vesicles freeze-dried with and without disaccharides and oxyanion-disaccharide complexes. Some of our results to date are shown in Figure 9.3. 

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