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. 2023 Mar 24;24(7):6190.
doi: 10.3390/ijms24076190.

Experimental Studies on the Thermal Properties and Decomposition Course of a Novel Class of Heterocyclic Anticancer Drug Candidates

Marta Worzakowska  1 , Małgorzata Sztanke  2 , Krzysztof Sztanke  3
Affiliations

Experimental Studies on the Thermal Properties and Decomposition Course of a Novel Class of Heterocyclic Anticancer Drug Candidates

Marta Worzakowska et al. Int J Mol Sci. .

Abstract

The experimental studies on the thermal properties and decomposition course of a novel class of potential anticancer drugs (1-5) containing in their heterobicyclic structures the asymmetrical triazine template were performed with the use of differential scanning calorimetry (DSC) and simultaneous thermogravimetry/differential scanning calorimetry (TG/DTG/DSC) coupled online with Fourier transform infrared spectroscopy (FTIR) and quadrupole mass spectrometry (QMS) in inert and oxidizing conditions. All the compounds were thermally characterized in detail for the first time in this article. The DSC studies proved that the melting points of the tested compounds depended on the position and type of the substituent at the phenyl moiety, whereas they did not depend on the furnace atmosphere. All the tested polynitrogenated heterocycles proved to be molecules with high thermal stability in both atmospheres, and most of them (1, 3-5) were more stable in oxidizing conditions, which indicated the formation of a more thermally stable form of the compounds when interacting with oxygen. The simultaneous TG/FTIR/QMS analyses confirmed that their pyrolysis process occurred in one main stage resulting in the emission of volatiles such as NH3, HNCO, HCN, CO, CO2, H2O, NO2, aromatic amine derivatives, alkenes (for compounds 1-5), and HCl (for the compound 5). On the other hand, the oxidative decomposition process was more complicated and proceeded in two main stages leading to the emission of NH3, CO2, CO, HCN, HNCO, H2O, some aromatics (for compounds 1-5), HCl (for compounds 3-5) as well as the additional volatiles such as N2, NO2, NH2OH, and (CN)2. The type of the formed volatiles indicated that the decomposition process of the studied heterocycles under the influence of heating was initiated by the radical mechanism. Their decomposition was related to the symmetric cleavage of C-N and C-C bonds (inert conditions) and additional reaction of the volatiles and residues with oxygen (oxidizing conditions).

Keywords: TG/DTG/DSC; TG/FTIR/QMS; annelated asymmetrical triazines; heterocyclic anticancer drug candidates; radical mechanism; thermal decomposition course; thermal stability.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of the investigated heterocycles: 1. R = H; 2. R = 4-CH3; 3. R = 3-Cl; 4. R = 4-Cl; 5. R = 3,4-Cl2. The particular derivatives differ in the substitution pattern (denoted as R) at the phenyl ring.
Figure 2
Figure 2
The DSC curves for compounds 1–5 (a helium atmosphere).
Figure 3
Figure 3
The TG (a), DTG (b), and DSC (c) curves of compounds 1–5 (a helium atmosphere).
Figure 4
Figure 4
The FTIR spectra of volatiles emitted under the heating of the tested compounds 1–5 (a helium atmosphere).
Figure 5
Figure 5
The enlarged FTIR spectrum for compound 2 with marked decomposition products.
Figure 6
Figure 6
The QMS spectra of volatiles emitted under the heating of the selected compounds (an inert atmosphere).
Scheme 1
Scheme 1
The pyrolysis products of the tested compounds formed in inert conditions.
Figure 7
Figure 7
The TG (a), DTG (b), and DSC (c) curves of compounds 1–5 (a synthetic air atmosphere).
Figure 8
Figure 8
The gaseous FTIR spectra of volatiles emitted under the heating of the tested compounds in an oxidizing atmosphere.
Figure 9
Figure 9
The QMS spectra collected at Tmax1 and Tmax2 for the selected compounds in an air atmosphere.
Scheme 2
Scheme 2
The decomposition mechanism: the products of the tested compounds formed in oxidizing conditions.
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