Novel NO₂ semicarbazone ligand and its metal complexes as VEGFR‐2 inhibitors: Synthesis, spectral characterization, density functional theory calculations, molecular docking, and antimicrobial and antitumor evaluation

Abstract

A novel semicarbazone NO 2 ligand, H 2 L, was synthesized. The ligand reacted with several metal ions such as Cu(II), Ni(II), Co(II), Fe(III), Cr(III), and Mn(II) in a molar ratio 1:1 (M:L). The H 2 L ligand and its metal complexes were characterized by electronic, infrared, mass, nuclear magnetic resonance, electron spin resonance spectra, as well as elemental analysis, thermal analysis, molar conductance, and magnetic susceptibility measurements. The Coats-Redfern equations were used to calculate the kinetic parameters (E a , A, ΔH, ΔS, and ΔG) of the thermal decomposition stages. The H 2 L ligand acts as dianionic NO 2 tridentate in all complexes and coordinates through enolate oxygen, azomethine nitrogen, and deprotonated OH group. The geometrical arrangements in all metal complexes were octahedral geometries. Based on density functional theory (DFT) level implemented in the Gaussian 09 program at B3LYP/6-311G(d,p) level, the molecular structural parameters of the ligand and its metal complexes were calculated, and the theoretical data were connected with the experimental results. The antimicrobial activity of the current compounds was examined against Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram-negative bacteria (Salmonella typhimurium and Escherichia coli), yeast (Candida albicans), and fungus (Aspergillus fumigatus). The antitumor activity of the ligand and its metal complexes was investigated against HepG2 cell line, which revealed promising IC 50 values comparable with that of Cis-platin. All synthesized compounds were also subjected to molecular docking studies to investigate their binding pattern and affinity for the VEGFR-2 active site and correlated with antitumor data.

Comments on multiple publications reporting single heating rate kinetics

“…The purpose of this note is to alert the Applied Organometallic Chemistry community to an alarming number of publications that report the single heating rate kinetics for thermal decomposition of compounds. According to Scopus, [ 1 ] most recently (i.e., in the years 2021 and 2022) this journal published 21 papers [ 2–22 ] that study the thermal decomposition kinetics as measured by thermogravimetry at a single heating rate. The resulting measurements are treated by means of the Coats–Redfern [ 23 ] or Horowitz–Metzger [ 24 ] method in order to evaluate the kinetic parameters, that is, the activation energy, E, preexponential factor, A, and reaction model, g(α) .…”

“…As a rule, for decomposition the activation energy values markedly smaller than 100 kJ mol À1 should raise suspicion. Yet, the majority of the aforementioned publications report the values less than 50 kJ mol À1 and some of them less than 10 [3,6,11,14,21,22] and even less than 1 [6] kJ mol À1 . If such energy barriers were real, the respective compounds would unlikely be stable at ambient temperature.…”

“…The compound is [Fe(L)(H 2 O) 2 (EtOH)]NO 3 ÁH 2 O, and its details are described elsewhere. [21] Table 1 lists the reported kinetic parameters, E, A, and the reaction order, n for the three steps of decomposition. These parameters can be readily used to estimate how long it takes for the compound to reach certain extent of decomposition at any given temperature.…”

“…[27] Overall, it is hoped that this short note is convincing enough for the community to uniformly adopt the multiple heating rate methodology. T A B L E 1 Kinetic parameters determined [21] by the Coats-Redfern method…”

Pyranoquinolone derivatives: A potent multi‐targeted pharmacological scaffold

“…One of the most interesting nitrogenous heterocycles are these molecules. Pyranoquinolone derivatives, both natural and synthetic, carry an extensive spectrum of medicinal and pharmacologic impacts, including anticoagulant properties [31], antitumor impact [32], microbial growth suppression [33], fungal treatment as well as anti-tubulin [34], anti-amoebiasis, anti-schistosomal [31][32][33][34][35][36][37][38], and anti-tuberculous measures [39][40][41][42]. Bio-organic chemistry relies on pyranoquinolone like molecules [43].…”