Inclusion of Vitamin E in 1D Nanochannels of 2,4,6-Tris(4-chlorophenoxy)-1,3,5-triazine: Structural and Thermal Characterization of a Stable Solid-State Complex

Abstract

Vitamin E (VE; (±)-α-tocopherol) is a potent antioxidant that plays a critical role in protecting cells from oxidative stress. However, its effectiveness is hindered by its susceptibility to oxidation during storage and poor absorption in the digestive system. Conventional stabilization methods often rely on chemical modifications or the excessive use of excipients, which can reduce VE's effectiveness. Therefore, a delivery system capable of preserving the antioxidant properties of VE without altering its chemical structure is essential. In this study, we develop an inclusion compound in which VE is encapsulated within the 1D nanochannels of 2,4,6-tris-(4-chlorophenoxy)-1,3,5-triazine (CLPOT), forming [(CLPOT)₂-(VE)_0.49]. These nanochannels physically isolate VE from environmental oxidizing agents to prevent oxidation. In addition, structural and thermal analyses, including powder and single-crystal X-ray diffraction, thermogravimetry-differential thermal analysis, and solution (¹H or ¹³C) and solid-state (¹³C) nuclear magnetic resonance, confirm stable incorporation of VE into the CLPOT nanochannels consisting of periodical hexagonal CLPOT crystals without requiring chemical modification. Compared with conventional encapsulation techniques, this method provides enhanced protection by creating a confined and protective environment. These findings suggest that CLPOT-based systems offer a promising platform for stabilizing and delivering fat-soluble nutrients, such as VE.

1

Chemical structures of the guest compound used in this study with nonequivalent carbon atoms numbered (refer to Sections and ).

2

Solution ¹H NMR spectra at 11.7 T (500 MHz) of (a) guest-free CLPOT, (b) VE, (c) compound 2 ([(CLPOT)₂-(VE)_0.06]), and (d) compound 1 ([(CLPOT)₂-(VE)_0.49]). The signals for the residue proton of the solvent CDCl₃ (δ = 7.25 ppm), water dissolved in CDCl₃ (δ = 1.54 ppm), and tetramethylsilane (δ = 0.01 ppm) were truncated for clarity in each spectrum. The “rg” in the figures means the values of the receiver gain.

3

Solution ¹³C NMR spectra at 11.7 T (500 MHz) of (a) guest-free CLPOT, (b) VE, (c) compound 2, and (d) compound 1. The signal of CDCl₃ (δ = 77.4 ppm) in each spectrum was truncated for clarity.

4

Room-temperature powder XRD patterns of (a) guest-free CLPOT, (b) compound 2, and (c) compound 1.

5

Crystal structure of 1 at 173 K, illustrating a unit cell with dimensions of 2a×2b × c/2 along the c-axis direction. The upper layer of the unit cell is positioned at the 6₃-glide symmetric position along the c-axis. The magenta circle indicates the CLPOT nanochannel, oriented parallel to the c-axis of the crystal.

6

TG (upper) and DTA (bottom) curves for (a) guest-free CLPOT (black), (b) compound 2 (green), (c) compound 1 (red), and (d) oily VE (cyan) over the temperature range of 50–400 °C.

7

Snapshots of compound 1 recorded during the sample observation of TG-DTA at (a) 100, (b) 188, and (c) 207 °C.

8

Solution and solid-state ¹³C NMR spectra at 11.7 T (500 MHz) of compound 1: (a) VE dissolved in CDCl₃ for comparison (note that this spectrum is the same as in Figure d), (b) CP/MAS spectrum at 293 K, and PST/MAS spectra at (c) 293 and (d) 333 K. Down arrows in panel (b) indicate the C_1’–C_5′ signals of CLPOT in compound 1 (see also Figure b and Section ), whereas other signals marked with different symbols represent suppressed spinning side bands. The spectra in panels (c) and (d) were normalized based on the signal assigned to C_1’ of CLPOT at 175.1 ppm, due to its lower mobility and minimal overlap with the VE signal.

9

Schematic representation of VE molecules incorporated into CLPOT nanochannels based on the findings of this study.