Facilitating Nitrification Inhibition through Green, Mechanochemical Synthesis of a Novel Nitrapyrin Complex

Abstract

Nitrapyrin (NP) is applied to cultivated soils to inhibit the enzymatic activity of ammonia monooxygenase (AMO), but its poor aqueous solubility and high volatility severely limit its application. β-Cyclodextrin (β-CD) is commonly used to form inclusion complexes with hydrophobic molecules, improving water solubility and stability upon complexation. Here we report on the mechanochemical synthesis of the inclusion complex β-CD•NP, characterized via a combination of solid-state techniques, including exsitu and in situ X-ray diffraction, Raman and NMR spectroscopies, transmission electron microscopy, and energy dispersive X-ray spectroscopy. The pure inhibitor NP was also structurally characterized. The β-CD•NP complex presents improved solubility and thermal stability, and still inhibits the enzymatic activity of AMO with high efficacy. All results indicate that the inclusion of NP into β-CD represents a viable route for the preparation of a novel class of inhibitors, with improved properties related to stability, water solubility, and good inhibition activity.

Thiocarbamoyl Disulfides as Inhibitors of Urease and Ammonia Monooxygenase: Crystal Engineering for Novel Materials

“…The large hydrophobicity of the thiurams under study, however, suggested an alternative route for the preparation of novel solid-state formulations, namely, their inclusion into β-cyclodextrin (β-CD). A similar approach has been recently reported, in which nitrapyrin, a known inhibitor of ammonia monooxygenase, was shown to form inclusion adducts, with improved water solubility, with β-CD …”

“…According to the principle of isostructurality, β-CD molecules generally crystallize in eight possible isostructural series, each of them characterized by similar cell parameters, and therefore by similar powder X-ray diffraction patterns, regardless of the chemical nature of the guest molecules. We recently employed this method for the characterization of β-CD inclusion compounds. , A Pawley refinement on the experimental pattern of (β-CD) 2 ·TETD provided a good match with the isostructural series corresponding to the channel-type crystal structure of β-CD dimers in the triclinic space group P 1 (see Figure a–c and Figure S4); in the case of β-CD·TMTD and (β-CD) 2 ·TIPTD, however, no isostructural series could be identified with certainty. We then turned to solid-state NMR spectroscopy (SSNMR, see below) to assess the stoichiometry of the TMTD and TIPTD complexes and compare their behavior with that of the TETD complex.…”

“…28 Disulfiram, together with its methyl derivative thiram (tetramethylthiuram disulfide, TMTD) had also been described as urease inhibitors, but little chemical and biochemical information is available. 29,30 In the present study, the efficiency of thiram, disulfiram, and their tetra-isopropyl derivative (TIPTD) (see Scheme 1) as inhibitors of the nitrification activity of N. europaea has been systematically explored. Contextually, the inhibition efficacy of the same compounds on the enzymatic activity of urease from Canavalia ensiformis (jack bean urease, JBU) has been investigated with the aim to develop a unique scheme to concurrently modulate the activity of these two key enzymes for soil nitrogen fertilization.…”

“…The enzymatic inhibition activity of TMTD, TETD, and TIPTD appeared considerably limited by their poor solubility in water. Following our recent successful attempt to increase the solubility of the nitrification inhibitor NP via encapsulation into hydrated β-cyclodextrin (β-CD•8H 2 O, indicated in the following simply as β-CD, Scheme 1), 29 a crystal engineering study 30 was undertaken to develop novel inclusion compounds of these three molecules with β-CD, that would feature higher water solubility. The syntheses of inclusion complexes of β-CD with TMTD, TETD, and TIPTD were thus performed by mechanochemical reactions of the pure reagents in the presence of a minimum amount of water (see Experimental Section).…”

Professor Roger Davey: Master ofAllCrystal Trades

“…Once in academia, Roger exploited his experience with ICI to be an effective collaborator with industry, understanding industrial perspectives and tailoring his scientific approach to solve their problems. The wide range of industries he has worked with is reflected here in contributions on batteries, agrochemicals, optoelectronics, − foodstuffs, , and fuels. However, it was the pharmaceutical industry that was to benefit most.…”