Authors: Raphael Lampl | Joscha Breibeck | Nadiia I. Gumerova | M. Galanski | Annette Rompel
Source: Scientific Reports (article, 2021-09-29)
Field: Materials Science — Materials Chemistry

Wells–Dawson phosphotungstates as mushroom tyrosinase inhibitors: a speciation study In order to elucidate the active polyoxotungstate (POT) species that inhibit fungal polyphenol oxidase (AbPPO4) in sodium citrate buffer at pH 6.8, four Wells-Dawson phosphotungstates [α/β-P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>18</sub>O<sub>62</sub>]<sup>6-</sup> (intact form), [α<sub>2</sub>-P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>17</sub>O<sub>61</sub>]<sup>10-</sup> (monolacunary), [P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>15</sub>O<sub>56</sub>]<sup>12-</sup> (trilacunary) and [H<sub>2</sub>P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>12</sub>O<sub>48</sub>]<sup>12-</sup> (hexalacunary) were investigated. The speciation of the POT solutions under the dopachrome assay (50 mM Na-citrate buffer, pH 6.8; L-3,4-dihydroxyphenylalanine as a substrate) conditions were determined by <sup>183</sup>W-NMR, <sup>31</sup>P-NMR spectroscopy and mass spectrometry. The intact Wells-Dawson POT [α/β-P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>18</sub>O<sub>62</sub>]<sup>6-</sup> shows partial (~ 69%) disintegration into the monolacunary [α<sub>2</sub>-P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>17</sub>O<sub>61</sub>]<sup>10-</sup> anion with moderate activity (K<sub>i</sub> = 9.7 mM). The monolacunary [α<sub>2</sub>-P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>17</sub>O<sub>61</sub>]<sup>10-</sup> retains its structural integrity and exhibits the strongest inhibition of AbPPO4 (K<sub>i</sub> = 6.5 mM). The trilacunary POT [P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>15</sub>O<sub>56</sub>]<sup>12-</sup> rearranges to the more stable monolacunary [α<sub>2</sub>-P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>17</sub>O<sub>61</sub>]<sup>10-</sup> (~ 62%) accompanied by release of free phosphates and shows the weakest inhibition (K<sub>i</sub> = 13.6 mM). The hexalacunary anion [H<sub>2</sub>P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>12</sub>O<sub>48</sub>]<sup>12-</sup> undergoes time-dependent hydrolysis resulting in a mixture of [H<sub>2</sub>P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>12</sub>O<sub>48</sub>]<sup>12-</sup>, [P<sup>V</sup><sub>8</sub>W<sup>VI</sup><sub>48</sub>O<sub>184</sub>]<sup>40-</sup>, [P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>19</sub>O<sub>69</sub>(H<sub>2</sub>O)]<sup>14-</sup> and [α<sub>2</sub>-P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>17</sub>O<sub>61</sub>]<sup>10-</sup> which together leads to comparable inhibitory activity (K<sub>i</sub> = 7.5 mM) after 48 h. For the solutions of [α/β-P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>18</sub>O<sub>62</sub>]<sup>6-</sup>, [α<sub>2</sub>-P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>17</sub>O<sub>61</sub>]<sup>10-</sup> and [P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>15</sub>O<sub>56</sub>]<sup>12-</sup> the inhibitory activity is correlated to the degree of their rearrangement to [α<sub>2</sub>-P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>17</sub>O<sub>61</sub>]<sup>10-</sup>. The rearrangement of hexalacunary [H<sub>2</sub>P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>12</sub>O<sub>48</sub>]<sup>12-</sup> into at least four POTs with a negligible amount of monolacunary anion interferes with the correlation of activity to the degree of their rearrangement to [α<sub>2</sub>-P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>17</sub>O<sub>61</sub>]<sup>10-</sup>. The good inhibitory effect of the Wells-Dawson [α<sub>2</sub>-P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>17</sub>O<sub>61</sub>]<sup>10-</sup> anion is explained by the low charge density of its protonated forms H<sub>x</sub>[α<sub>2</sub>-P<sup>V</sup><sub>2</sub>W<sup>VI</sup><sub>17</sub>O<sub>61</sub>]<sup>(10-x)-</sup> (x = 3 or 4) at pH 6.8. Chemistry ; Nuclear chemistry ; Polyphenol oxidase ; Nuclear magnetic resonance spectroscopy ; Substrate (aquarium) ; Enzyme ; Stereochemistry ; Biochemistry Polyoxometalates: Synthesis and Applications ; Vanadium and Halogenation Chemistry ; Advanced Nanomaterials in Catalysis