Influence of Incorporation of Different dn-Electron Metal Cations into Biologically Active System on Its Biological and Physicochemical Properties

Abstract

Three new compounds, namely [HL]2+[CuCl4]2−, [HL]2+[ZnCl4]2−, and [HL]2+[CdCl4]2− (where L: imipramine) were synthesized and their physicochemical and biological properties were thoroughly investigated. All three compounds form isostructural, crystalline systems, which have been studied using Single-Crystal X-ray diffraction analysis (SC-XRD) and Fourier-transform infrared spectroscopy (FTIR). The thermal stability was investigated using thermogravimetric analysis (TGA) and melting points for all compounds have been determined. Magnetic measurements were performed in order to study the magnetic properties of the compounds. The above mentioned techniques allowed us to comprehensively examine the physicochemical properties of the newly obtained compounds. The biological activity was investigated using the number of Zebrafish tests, as it is one of the most common models for studying the impact of newly synthesized compounds on the central nervous system (CNS), since this model is very similar to the human CNS.

Evaluation of Antidepressive-like Behaviours and Oxidative Stress Parameters in Mice Receiving Imipramine-Zinc Complex Compound

“…This issue arises when IMI and Zn are administered as separate oral treatments in animal and human experiments. Therefore, Rogalewicz et al [ 72 ] developed a methodology for obtaining and synthesizing an IMI-Zn complex compound, whose antidepressant activity in the FST in mice was assessed in these studies. The outcomes of the conducted investigation revealed that the IMI-Zn complex displayed an antidepressant-like effect that varied with dosage.…”

“…In the acute toxicity studies conducted using the Zebrafish model, the IMI-Zn complex compound was found to have no adverse effects on fish development. Additionally, it exhibited a dose-dependent impact on the spontaneous locomotor activity of 5-day-old larvae—higher doses of the IMI-Zn complex inhibited locomotor activity, while lower doses increased it [ 72 ]. Additionally, Rogalewicz et al [ 72 ] demonstrated that the IMI-Zn complex, specifically at a concentration of 3 μM, produced a similar anxiolytic-like effect in a light/dark test compared to diazepam, a commonly used anxiolytic drug.…”

“…Additionally, it exhibited a dose-dependent impact on the spontaneous locomotor activity of 5-day-old larvae—higher doses of the IMI-Zn complex inhibited locomotor activity, while lower doses increased it [ 72 ]. Additionally, Rogalewicz et al [ 72 ] demonstrated that the IMI-Zn complex, specifically at a concentration of 3 μM, produced a similar anxiolytic-like effect in a light/dark test compared to diazepam, a commonly used anxiolytic drug. The authors further showed that the impact of each tested concentration of the IMI-Zn complex differed from those of IMI alone, suggesting that the addition of Zn modified the effect of IMI on the central nervous system [ 72 ].…”

“…The following substances were used in the conducted research: imipramine hydrochloride (IMI, Sigma-Aldrich, Poznań, Poland) at a dose of 60 mg/kg and 90 mg/kg, i.e., 53.096 and 79.644 mg/kg pure IMI (subtherapeutic and effective dose, respectively); zinc hydroaspartate (Zn, Farmapol, Poznań, Poland) at a dose of 40 mg/kg and 80 mg/kg (calculated as pure Zn 2+ ions; subtherapeutic and effective dose, respectively); imipramine-zinc complex (IMI-Zn, [HL] 2+ [ZnCl 4 ] 2− (where L: IMI) was synthesized at the Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, Lodz, Poland [ 72 ]. The IMI-Zn complex was administered in the dose range of 5–100 mg/kg (the percentage of Zn in 1 mg of the administered complex is 84.9 µg and 731 µg of IMI).…”

“…Animals from the control group received 0.9% NaCl. Doses of tested substances and administration schedules were chosen based on our earlier studies and literature data [ 70 , 72 ].…”