Thermal Decomposition Path-Studied by the Simultaneous Thermogravimetry Coupled with Fourier Transform Infrared Spectroscopy and Quadrupole Mass Spectrometry-Of Imidazoline/Dimethyl Succinate Hybrids and Their Biological Characterization

Abstract

The thermal decomposition path of synthetically and pharmacologically useful hybrid materials was analyzed in inert and oxidizing conditions for the first time and presented in this article. All the imidazoline/dimethyl succinate hybrids (1-5) were studied using the simultaneous thermogravimetry (TG) coupled with Fourier transform infrared spectroscopy (FTIR) and quadrupole mass spectrometry (QMS). It was found that the tested compounds were thermally stable up to 200-208 °C (inert conditions) and up to 191-197 °C (oxidizing conditions). In both furnace atmospheres, their decomposition paths were multi-step processes. At least two major stages (inert conditions) and three major stages (oxidizing conditions) of their decomposition were observed. The first decomposition stage occurred between T_5% and 230-237 °C. It was connected with the breaking of one ester bond. This led to the emission of one methanol molecule and the formation of radicals capable of further radical reactions in both used atmospheres. At the second decomposition stage (T_max2) between 230-237 °C and 370 °C (inert conditions), or at about 360 °C (oxidizing conditions), the cleavage of the second ester bond and N-N and C-C bonds led to the emission of CH₃OH, HCN, N₂, and CO₂ and other radical fragments that reacted with each other to form clusters and large clusters. Heating the tested compounds to a temperature of about 490 °C resulted in the emission of NH₃, HCN, HNCO, aromatic amines, carbonyl fragments, and the residue (T_max2a) in both atmospheres. In oxidizing conditions, the oxidation of the formed residues (T_max3) was related to the production of CO₂, CO, and H₂O. These studies confirmed the same radical decomposition mechanism of the tested compounds both in inert and oxidizing conditions. The antitumor activities and toxicities to normal cells of the imidazoline/dimethyl succinate hybrids were also evaluated. As a result, the two hybrid materials (3 and 5) proved to be the most selective in biological studies, and therefore, they should be utilized in further, more extended in vivo investigations.

Keywords: antihemolytic activity; antitumor activity; decomposition course; imidazoline/dimethyl succinate hybrids; thermal behavior; toxicity to normal cells.

Figure 1

Structures of the investigated hybrid materials, i.e., dimethyl 2-{2-[1-(R-phenyl)-4,5-dihydro-1H-imidazol-2-yl]hydrazinylidene}succinates: 1. R = H, 2. R = 4-CH₃, 3. R = 4-OCH₃, 4. R = 4- OCH₂CH₃, and 5. R = 4-Cl.

Figure 2

The DSC curves for the tested molecules.

Figure 3

The possible structural isomers of compounds 3 and 4. I. Dimethyl (2E)-2-{2-[1-(4-methoxy/4-ethoxyphenyl)-4,5-dihydro-1H-imidazol-2-yl]hydrazinylidene}butanedioate. II. Dimethyl (2E)-2-{2-[1-(4-methoxy/4-ethoxyphenyl)-4,5-dihydro-1H-imidazol-2-yl]hydrazinyl}but-2-enedioate. III. Dimethyl (2E)-2-{(2Z)-[1-(4-methoxy/4-ethoxyphenyl)imidazolidin-2-ylidene]hydrazinylidene}butanedioate. IV. Dimethyl (2E)-2-{(2Z)-2-[1-(4-methoxy/4-ethoxyphenyl)imidazolidin-2-ylidene]hydrazinyl}but-2-enedioate. R = CH₃ (compound 3) or CH₂CH₃ (compound 4).

Figure 4

The TG/DTG curves for the tested compounds in inert conditions.

Figure 5

The TG/DTG curves for the tested compounds in oxidizing conditions.

Figure 6

The exemplary gaseous 3D FTIR spectra for compounds 1 and 5.

Figure 7

The gaseous FTIR spectra for the tested compounds 1–5 (a helium atmosphere).

Figure 8

The standard spectrum of gaseous methanol according to the NIST database [26].

Scheme 1

The decomposition path of the tested compounds in inert conditions.

Figure 9

The QMS spectra collected at T_max1 and T_max2 for all the tested compounds.

Figure 10

The QMS spectra at T_max2a for compound 1 (a), compound 2 (b), compound 3 (c), compound 4 (d), and compound 5 (e).

Figure 11

The exemplary gaseous 3D FTIR spectra for compounds 1 and 4.

Figure 12

The gaseous FTIR spectra for the tested compounds 1–5 (a synthetic air atmosphere).

Figure 13

The QMS spectra at T_max1, T_max2, and T_max3 for all the tested compounds (common graphs).

Figure 14

The QMS spectra for the volatiles emitted at T_max2a in a synthetic air atmosphere.

Figure 15

Antiproliferative activity of all the investigated compounds (1–5) against human tumor cells, as well as their cytotoxicity towards normal cells. Normal cell line: Vero—(ECACC 88020401)—African green monkey kidney cells. Tumor cell lines: TOV112D (ATCC CRL-11731)—human ovarian primary malignant adenocarcinoma cells; and HeLa (ECACC 93021013)—human Negroid cervix epitheloid carcinoma cells. Compound 5 was not active against TOV112D cells, while compounds 1–4 were not active against HeLa cells.