Exploring neat grinding and liquid-assisted-grinding to obtain different polymorphs of curcumin and its Schiff base curcumin derivatives Aniele De Moura a , Alexandre Cuin b , Flávio Junior Caires a a UNESP, School of Sciences, Chemistry Department, Brazil, b Chemistry Department, Federal University of Juiz de Fora, Brazil Curcumin is a turmeric that presents several biological applications, among them: antioxidant, anti-inflammatory, and antitumor activity, however, it presents low bioavailability, due to its low solubility in water. 1 To overcome this problem, several researchers work on the development of curcumin derivatives, such as Schiff bases, which can potentialize its properties. In this way, the eco-friendly mechanochemical method was applied to obtain a curcumin glycine Schiff base derivative (CGD). 2 The syntheses were carried out in a Restch mixer mill 400 MM, under 20 Hz of frequency, sing a stainless-steel jar (10 mL) and a stainless-steel ball (7 mm). The authors have also evaluated if CGD could be obtained by neat-grinding (NG) and Liquid-Assisted-Grinding (LAG). After the NG synthesis, it was observed a product with an orange coloration (NG CGD), while at the end of the LAG synthesis it was observed a yellow compound (LAG CGD). These compounds were evaluated by ¹H NMR, which confirmed the obtention of the Schiff bases. The liquid used in LAG syntheses can enable the generation of several polymorphs, therefore, NG CGD and LAG CGD were analyzed by XRD (powder), and the results suggested that it was obtained two polymorphs for each synthesis (Figure 1.a). Moreover, it is the knowledge 3 polymorphs of curcumin (CUR), which normally can be obtained by using organic solvents through different crystallization methods, then it was evaluated if curcumin (CUR) could generate different polymorphs under solid-state synthesis. 1 CUR was milled, using the same conditions applied for CGD, as a result, it was observed that it displays different colorations at the end of NG (orange product) and LAG (yellow product) syntheses. The XRD diffractograms confirmed the obtention of different polymorphs (Figure 2.a). Comparing the experimental and theoretical diffractogram of curcumin, it was observed that NG CUR presents a mixture of polymorphs in Form I and III, while the LAG presents a polymorphic structure related to the Form I. 2
Figure 1. XRD powder diffractograms of NG and LAG CGD (a), CUR, NG CUR and LAG CUR (c), and, CGD milled with different amounts of ethanol (c).
Furthermore, it has been already reported that the amount of liquid in LAG synthesis is a parameter that influences the obtention of polymorphs, 2 therefore, the authors evaluated how the amount of liquid can influence in CGD polymorphism. The diffractograms displayed in Figure 1.c show that the polymorphism interconversion occurs with an eta parameter (h) higher than 0.06 mL/mg. In summary, the authors concluded that the mechanochemical method can be applied to obtain different polymorphs of curcumin and its curcumin-glycine Schiff base, in addition, a liquid can be used to control the polymorphic form of these compounds, considering an h ≈ 0.07-0.16- μL/mg for each synthesis. References
1. New polymorphs of curcumin. Chem Comm . 2011. 2. Mechanochemistry for Synthesis. Angew Chem . 2020.
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© The Author(s), 2022
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