Introduction

Currently, one of the most widely used pharmaceutical compounds to control hyperglycemia in patients with T2D is metformin hydrochloride (a biguanide derivative) due to its effectiveness and good safety profile.3 However, it is also associated with ad...

Experimental section

General information

Thermogravimetric analysis (TGA) was performed in a TA instrument (Discovery SDT 650) under the following conditions: 25-900 °C temperature range, under nitrogen (100 mL min−1 flow) atmosphere, and 20 °C min−1 heating rate. Fourier-transform infrared spectrophotometry (FTIR) spectra were recorded from KBr pellets in the 4000-250 cm−1 range on a Shimadzu IRAffinity-1.

Synthesis of the [Co(C4H11N5)3]Cl2·2H2O complex (compound 1)

Synthesis of the [Ni(C4H11N5) (C4H10N5)]Cl·H2O complex (compound 2)

Synthesis of the [Cu(C4H11N5)2]Cl2·2H2O complex (compound 3)

Synthesis of the [Zn(C4H12N5) Cl3] complex (compound 4)

Single-crystal X-ray diffraction (SCXRD) for structure determination

Cell cultures

To evaluate cell viability, HepG2 and C2C12 cells were seeded in 96 multi-well plates at a density of 2.5 × 104 cells per well and cultured for 24 h. The cells were washed once with DMEM and then incubated with different concentrations of extracts or fractions (1000, 500, 250, 125, 62.5, 31.25 μg mL−1) in DMEM for 4 h (C2C12) or 48 h (HepG2). The negative control is formed by cell culture medium with the same cell concentration and 0.05% of DMSO. Insulin 0.3 mM (INS) and metformin 5 mM (MET) are used as positive control. Subsequently, the medium was removed, cells were washed once, and MTT (5 mg mL−1) in DMEM was added to each well and incubated for 4 h. The MTT-containing medium was removed, and 200 μL of DMSO were added to dissolve the formazan crystals. The optical densities (OD) were measured using a Varioskan Flash spectrophotometer (Thermo, Waltham, MA, USA) at 570 nm.26

Results and discussion

The [Co(C4H12N5)3]Cl2·H2O compound (1) was obtained as cubic reddish crystals that crystallized in the C2/c monoclinic space group with one molecule of the cationic complex, two chloride anions, and one molecule of water in the asymmetric unit (Fig. 1a). The...

Supramolecular interactions analysis

It is also possible to observe that in all the cases, the strongest and most important contributions to the crystal packing is given for N⋯H, O⋯H, and H⋯Cl interactions, characterized by the presence of narrow peaks in the bottom of the finger print plots. In addition, we observed important interactions, including C⋯H and H⋯H, where the H⋯H interactions are the more abundant interactions in the crystal packing (Fig. 12). Only in the Zn complex, we observed a high contribution of H⋯Cl interactions in the formation of the crystal packing. The different interaction values observed in all cases are characteristic of the nature of each complex and its crystal packing (Fig. 12).

Vibrational spectroscopy and thermal analysis

The metal-metformin complexes show a similar thermal profile (ESI S2‡) with an initial mass loss for free water of 6.87%, 5.8%, and 8.1% (Tonset = 82, 67, 80 °C) for compounds 1, 2, and 3, respectively. These mass losses are in agreement with the calculated values for two water molecules for 1 (6.72%) and 3 (8.3%) and one molecule for 2 (4.9%). The compounds 1, 2, 3, and 4 exhibit a decomposition temperature around 240 °C, 312 °C, 238 °C, and 221 °C (Tonset), respectively.

Cytotoxicity test

Conclusions

Conflicts of interest

Acknowledgements

Notes and references

Footnotes