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Scheme 3.6

Compound 3.6 was obtained by acylation of compound 1.57 with 5-phenyltetrazol- 2-ylacetic acid chloride (3.5) (Scheme 3.6). The reaction was carried out at room temperature in acetonitrile (MeCN) in the presence of triethylamine, followed by purification of the resulting product by column chromatography. The yield of the target product was 54 % [28].

Compound 3.6 was characterised by mass spectrometry and 1H, 13C{H} NMR and IR spectroscopy. In the 1H NMR spectrum of compound 3.6, there are signals at 1.36 and 1.45 ppm corresponding to the chemical shifts of the protons of the CH3-groups in the dioxane ring. The signal of the protons of the methylene groups of the aziridine rings located in the 2- and 4-positions of the substituted 1,3,5-triazine was observed at 2.31 ppm. In the region of 8.12–8.17 ppm, there were signals of the benzene ring 5-phenyltetrazol-2- yl fragment. In the 13C{H} NMR spectrum of compound 3.6, the signal at 164.8 ppm corresponded to the endocyclic carbon atom of the N(2)-substituted tetrazolyl ring. The carbon atom signal of the methylene group of the 5-phenyltetrazol-2-yl-acetyl fragment was observed at 65.1 ppm [28].

Thus, the possibility of using the reaction of acylation of the hydroxymethyl group of compound 3.6 with tetrazolylacetic acid halides was shown.

3.3. Synthesis and identification of the GO-1.57 conjugate

In this work, a noncovalent GO conjugate with compound 1.57 was synthesised. To obtain a non-covalent conjugate of GO with compound 1.57, the following procedure was used: 1 g of GO was dispersed in an alkaline medium (pH 9; 200 ml) by sonication for 15

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Fig. 3.3. 13C NMR spectra of GO and GO-1.57 conjugate (down up: 13C NMR spectrum of the compound 1.57; 13C NMR spectrum of GO; 13C NMR spectrum of a mixture obtained by physical adsorption; 13C NMR spectrum of GO-1.57).

The XPS spectra of GO-1.57 (Fig. 3.4a) show peaks C 1s (285 eV), O 1s (532 eV), N 1s (400 eV). Fig. 3.4b shows the result of deconvolution of the 1s carbon peak with the formation of four peaks at the following binding energies: 284 eV (C=C groups of the aromatic domain on the graphene surface), at 285 eV (C–C groups of the graphene skeleton), at 287 eV (C–N amide bond groups), at 289 eV (C–O of epoxy and hydroxyl groups on the surface of GO-1.57). Deconvolution of the 1s oxygen peak leads to the formation of the following signals (Fig. 3.4c): 533 eV, related to the O–H groups (carboxyl and also GO hydroxyl groups); 532 eV, related to the C–O groups (as part of the epoxy, carboxyl, and hydroxyl groups on the surface of GO). Fig. 3.4d shows the result of the deconvolution of the 1s nitrogen peak with the formation of a peak at 402 eV (aziridine groups of compound 1.57) and also at 399 eV (nitrogen atoms in the composition of the triazine ring).

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Fig. 3.4. XPS spectra of GO-1.57.

According to the obtained thermogravimetric (TG) and differential thermal (DTG) curves, it is clear that the decomposition of GO-1.57 took place in several stages (Fig. 3.5).

A significant weight loss was observed at 95 °C, which may be due to the presence of adsorbed water molecules. At 183 °C, a noticeable weight loss was observed due to the degradation of compound 1.57 adsorbed on the GO surface. The resulting weight loss is consistent with the loading percentage of compound 1.57 (62 wt %). The weight loss of

GO at 338 °C is explained by various kinds of rearrangements involving functional groups on the GO surface and, finally, by further degradation of the graphene sheet surface (603

°C).

Fig. 3.5. Thermogram of the conjugate GO-1.57: TG (—), DTG (—).

The IR spectra of the GO-1.57 conjugate contain a peak at 3410 cm−1, which is characteristic of the stretching vibrations of the hydroxyl, carboxyl, and lactol groups. The signal of the secondary amine N–H appears at 1650 cm−1, 1460, and 1458 cm−1 for the aziridine groups; the signals of the dimethyl fragments of compound 1.57 appear at 1360 and 1390 cm−1.

The Raman spectrum of GO-1.57 contains the D, G, and 2D bands. In particular, in the case of a single-layer GO, I2D / IG = 2; lower I2D / IG values indicate an increase in the number of GO layers. For the synthesised non-covalent conjugate GO-1.57, the ratio I2D /

IG = 0,65, which indicates the multilayer structure of the nanomaterial. The ID/IG ratio allows one to estimate the degree of functionalisation of the GO surface. Analysis Fig. 3.6 indicates the presence of D and G bands at 1360 cm−1 and 1592 cm−1, which have an intensity ratio ID / IG = 0.97. The resulting ID / IG ratio is consistent with the data for GO enriched in oxygen-containing functional groups [81]. This fact indicates that the loading of compound 1.57 occurs due to physical adsorption.

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index, solubility, and stability of the compound depending on pH. The study of the physicochemical properties of aqueous solutions of biologically active compounds and potential drugs is the basis for understanding the mechanisms of their action, biodistribution, pharmacokinetics, pharmacodynamics, metabolic stability, etc. [82]. For example, data on density and viscosity characterise intermolecular interactions in solution, which makes it possible to predict the haemocompatibility of the test substance. The distribution coefficient makes it possible to predict the permeability of a substance through tissue and cellular barriers. Stability studies are necessary to understand the pharmacokinetics, pharmacodynamics, toxicokinetics, and metabolic stability of the test substance [83–93].

3.4.1. Density of aqueous solutions of compound 1.57

The results of studying the density of aqueous solutions of compound 1.57 (C = 0.025–10 g dm−3, T = 293.15–333.15 K) are shown in Fig. 3.8.

The average molar volumes and partial molar volumes of the solution components were calculated according to the equations:

is average molar volume; V is volume of an aqueous solution of a compound

1.57; nH2O , n1.57 and xH2O , x1.57 are amounts of substance and mole fractions of water and and V1.57 are partial molar volumes of water and compounds 1.57.

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Fig. 3.10. Concentration dependence of the partial molar volume of water at (□) 293.15 K, (○) 303.15 K, ( ) 313.15 K, ( ) 323.15 K, ( ) 333.15 K.

The results obtained demonstrate that at low concentrations up to 0.1 g∙dm−3, the values of V1.57 slightly decrease. This fact indicates that the addition of even a small amount of compound 1.57 leads to compression and structuring of the solution, hence, its stability over the entire measurement range.

3.4.2. Viscosity of aqueous solutions of the compound 1.57

Fig. 3.11 presents data on the dynamic (η) and (ηk) kinematic viscosity in the binary system compound 1.57 – water in the temperature range T = 293.15–333.15 K. The kinematic viscosity was calculated using formula 3.3 [86]:

C / гЧдм−3

Fig. 3.11. Concentration dependences of dynamic viscosity (η) at a shear rate of 100 s−1 in the binary system compound 1.57 – H2O at (□) 293.15 K, (○) 303.15 K, ( ) 313.15 K, ( ) 323 .15 K, ( ) 333.15 K. C is the concentration of the compound 1.57.

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