Stabilization of tryptamines by denaturing enzymes, optimizing ionization states, and controlling confounding variables

A composition, comprising tryptamines and a polypeptide, wherein:

• the tryptamines comprise phosphoryloxytryptamines and hydroxytryptamines;
• the phosphoryloxytryptamines comprise psilocybin and baeocystin;
• the psilocybin comprises both of (a) zwitterionic psilocybin, which comprises a monoanionic phosphonate ester and a cationic azanium, and (b) cationic psilocybin, which comprises an uncharged phosphonate ester and a second cationic azanium;
• the zwitterionic psilocybin and the cationic psilocybin each have the chemical formula [2-(4-phosphonooxy-1H-indol-3-yl)ethyl]-dimethylazanium, in which phosphonooxy is the monoanionic phosphonate ester in the zwitterionic psilocybin, and phosphonooxy is the uncharged phosphonate ester in the cationic psilocybin;
• the baeocystin comprises both of (c) zwitterionic baeocystin, which comprises a second monoanionic phosphonate ester and a third cationic azanium, and (d) cationic baeocystin, which comprises a second uncharged phosphonate ester and a fourth cationic azanium;
• the zwitterionic baeocystin and the cationic baeocystin each have the chemical formula [2-(4-phosphonooxy-1H-indol-3-yl)ethyl]-methylazanium, in which phosphonooxy is the second monoanionic phosphonate ester in the zwitterionic baeocystin, and phosphonooxy is the second uncharged phosphonate ester in the cationic baeocystin;
• the hydroxytryptamines comprise psilocin and norpsilocin;
• the psilocin comprises cationic psilocin, which lacks a phosphonate ester and comprises a fifth cationic azanium;
• the cationic psilocin has the chemical formula [2-(4-hydroxy-1H-indol-3-yl)ethyl]-dimethylazanium;
• the norpsilocin comprises cationic norpsilocin, which lacks a phosphonate ester and comprises a sixth cationic azanium;
• the cationic norpsilocin has the chemical formula [2-(4-hydroxy-1H-indol-3-yl)ethyl]-methylazanium;
• the zwitterionic psilocybin and the cationic psilocybin each have a rate of spontaneous dephosphorylation per mole in the composition, which converts the psilocybin into additional psilocin;
• the rate of spontaneous dephosphorylation for the zwitterionic psilocybin per mole of the zwitterionic psilocybin is less than the rate of spontaneous dephosphorylation for the cationic psilocybin per mole of the cationic psilocybin in the composition;
• the composition comprises the zwitterionic psilocybin and the cationic psilocybin at a mole ratio of at least 15:1 (zwitterionic psilocybin:cationic psilocybin);
• the mole ratio of at least 15:1 for the zwitterionic psilocybin and the cationic psilocybin in the composition results in a lower rate of spontaneous dephosphorylation for the psilocybin of the composition per mole of the psilocybin relative to a lower mole ratio of less than 15:1;
• the zwitterionic baeocystin and the cationic baeocystin each have a rate of spontaneous dephosphorylation per mole in the composition, which converts the baeocystin into additional norpsilocin;
• the rate of spontaneous dephosphorylation for the zwitterionic baeocystin per mole of the zwitterionic baeocystin is less than the rate of spontaneous dephosphorylation for the cationic baeocystin per mole of the cationic baeocystin in the composition;
• the composition comprises the zwitterionic baeocystin and the cationic baeocystin at a mole ratio of at least 15:1 (zwitterionic baeocystin:cationic baeocystin);
• the mole ratio of at least 15:1 for the zwitterionic baeocystin and the cationic baeocystin in the composition results in a lower rate of spontaneous dephosphorylation for the baeocystin per mole of the baeocystin of the composition relative to a lower mole ratio of less than 15:1;
• the psilocybin and the psilocin each have a different rate of spontaneous oxidation per mole in the composition;
• the rate of spontaneous oxidation for the psilocybin per mole of the psilocybin is less than the rate of spontaneous oxidation for the psilocin per mole of the psilocin in the composition;
• the composition comprises the psilocybin and the psilocin at a mole ratio of at least 3:2 (psilocybin:psilocin);
• the mole ratio of at least 3:2 for the psilocybin and the psilocin in the composition results in a lower rate of spontaneous oxidation for the tryptamines per mole of the tryptamines of the composition relative to a lower mole ratio of less than 3:2;
• the baeocystin and the norpsilocin each have a different rate of spontaneous oxidation per mole in the composition;
• the rate of spontaneous oxidation for the baeocystin per mole of the baeocystin is less than the rate of spontaneous oxidation for the norpsilocin per mole of the norpsilocin in the composition;
• the composition comprises the baeocystin and the norpsilocin at a mole ratio of at least 3:2 (baeocystin:norpsilocin);
• the mole ratio of at least 3:2 for the baeocystin and the norpsilocin in the composition correlates with a lower rate of spontaneous oxidation for the tryptamines per mole of the tryptamines of the composition relative to a lower mole ratio of less than 3:2;
• the polypeptide has at least 90 percent sequence identity with the amino acid sequence set forth in SEQ ID NO:
• 3;
• the polypeptide is denatured in the composition such that the polypeptide lacks laccase enzyme activity;
• the composition comprises the psilocin and the one or more oxidized diol dimers of psilocin at a mole ratio of at least 10:1 (psilocin:oxidized diol dimers);
• the mole ratio of at least 10:1 for the psilocin and the oxidized diol dimers of psilocin in the composition is indicative of effective denaturation of the polypeptide to inhibit laccase enzyme activity relative to a lower mole ratio of less than 10:1;
• each of the one or more oxidized diol dimers of psilocin is a dication that comprises two monocationic azaniumyl groups such that each of the one or more oxidized diol dimers of psilocin has an approximate molecular weight of 409 atomic mass units;
• the one or more oxidized diol dimers of psilocin comprise 3-[2-(dimethylazaniumyl)ethyl]-2-{3-[2-(dimethylazaniumyl)ethyl]-4-hydroxy-1H-indol-2-yl}-1H-indol-4-ol;
• the composition comprises the norpsilocin and the one or more oxidized diol dimers of norpsilocin and psilocin at a mole ratio of at least 10:1 (norpsilocin:oxidized diol dimers of norpsilocin and psilocin);
• the mole ratio of at least 10:1 for the norpsilocin and the oxidized diol dimers of norpsilocin and psilocin in the composition is indicative of effective denaturation of the polypeptide to inhibit laccase enzyme activity relative to a lower mole ratio of less than 10:1;
• each of the one or more oxidized diol dimers of norpsilocin and psilocin is a dication that comprises two monocationic azaniumyl groups such that each of the one or more oxidized diol dimers of norpsilocin and psilocin has an approximate molecular weight of 395 atomic mass units;
• the one or more oxidized diol dimers of norpsilocin and psilocin comprise 3-[2-(dimethylazaniumyl)ethyl]-2-{3-[2-(methylazaniumyl)ethyl]-4-hydroxy-1H-indol-2-yl}-1H-indol-4-ol;
• the composition comprises the psilocin and the one or more oxidized ylidene dimers of psilocin at a mole ratio of at least 10:1 (psilocin:oxidized ylidene dimers);
• the mole ratio of at least 10:1 for the psilocin and the oxidized ylidene dimers of psilocin in the composition is indicative of effective denaturation of the polypeptide to inhibit laccase enzyme activity relative to a lower mole ratio of less than 10:1;
• each of the one or more oxidized ylidene dimers of psilocin is a dication that comprises two monocationic azaniumyl groups such that each of the one or more oxidized ylidene dimers of psilocin has an approximate molecular weight of 407 atomic mass units;
• the oxidized ylidene dimers of psilocin comprise 3-[2-(dimethylazaniumyl)ethyl]-2-{3-[2-(dimethylazaniumyl)ethyl]-4-hydroxyindol-2-ylidene}indol-4-ol or a tautomer thereof;
• the composition comprises the norpsilocin and the oxidized ylidene dimers of norpsilocin and psilocin at a mole ratio of at least 10:1 (norpsilocin:oxidized ylidene dimers of norpsilocin and psilocin);
• the mole ratio of at least 10:1 for the norpsilocin and the oxidized ylidene dimers of norpsilocin and psilocin in the composition is indicative of effective denaturation of the polypeptide to inhibit laccase enzyme activity relative to a lower mole ratio of less than 10:1;
• each of the one or more oxidized ylidene dimers of norpsilocin and psilocin is a dication that comprises two monocationic azaniumyl groups such that each of the one or more oxidized ylidene dimers of norpsilocin and psilocin has an approximate molecular weight of 392 atomic mass units;
• the oxidized ylidene dimers of norpsilocin and psilocin comprise 3-[2-(dimethylazaniumyl)ethyl]-2-{3-[2-(methylazaniumyl)ethyl]-4-hydroxyindol-2-ylidene}indol-4-ol or a tautomer thereof;
• the composition is a product that is produced by a process that comprises (w) providing a starting composition that comprises the psilocybin, the baeocystin, the psilocin, the norpsilocin, and a laccase enzyme, wherein the psilocybin of the starting composition comprises an initial amount of the zwitterionic psilocybin, and the baeocystin of the starting composition comprises an initial amount of the zwitterionic baeocystin;
• (x) denaturing the laccase enzyme to produce the denatured polypeptide;
• (y) converting some of the psilocybin of the starting composition into the zwitterionic psilocybin such that the composition comprises a final amount of the zwitterionic psilocybin that is greater than the initial amount of the zwitterionic psilocybin, and (z) converting some of the baeocystin of the starting composition into the zwitterionic baeocystin such that the composition comprises a final amount of the zwitterionic baeocystin that is greater than the initial amount of the zwitterionic baeocystin;
• and
• the process comprises concurrently performing (x) denaturing the laccase enzyme to produce the denatured polypeptide, (y) converting some of the psilocybin of the starting composition into the zwitterionic psilocybin, and (z) converting some of the baeocystin of the starting composition into the zwitterionic baeocystin.