1. Introduction
Thiosemicarbazones and
bisthiosemicarbazones are organic ligands whose skeletons have donor atoms such as nitrogen and sulfur. These compounds are obtained by the reaction of a thiosemicarbazide with aldehydes or ketones [
1]. The design and synthesis of this type of ligands has been extensively studied in recent decades due to their important properties: ion sensing [
2], catalytic [
3], magnetic [
4], pharmaceutical, and biological (antiviral, radioprotective, anti-inflammatory, antibacterial, antifungal and antitumoral) [
5].
With all this in mind, the coordination chemistry of these types of compounds and, therefore, their biological applications have been of great interest. Thus, in this work we report the design, synthesis, and characterization of a bisthiosemicarbazone ligand, H3LMe, a potential precursor of dinuclear metal-derived complexes.
2. Experimental Section
The
bisthiosemicarbazone ligand H
3L
Me synthesis was carried out by means of an imine condensation reaction between 2-hydroxyisophthalaldehyde and 4-methyl-3-thiosemicarbazide in ratio 1:2, using absolute ethanol as a solvent (
Figure 1). To promote the formation of the imine bond, acid catalysis was used by adding
p-toluensulfonic acid. The reaction mixture was refluxed for 4 h using a Dean−Stark trap to remove the released water.
Finally, the bisthiosemicarbazide ligand was isolated as a yellow solid, which was characterized by the usual techniques in the solid state and in solution.
H3LMe: Yield 0.722 g, (90%). Elemental analysis, Calc. for C12H16N6OS2: C, 44.4; H, 5.0; N, 25.9; S, 19.8. Found: C, 44.5; H, 5.0; N, 25.7; S, 19.9%. MS ESI+ (m/z): 325.1 [H3LMe+H]. IR (KBr, cm−1): ν(O-H) 3360 (m), ν(N-H) 3163 (m), ν(C=N + C-N) 1611 (m), 1541 (mf), 1497 (m), ν(C-O) 1231 (f) ν(C=S) 1094 (m), 800 (mf), υ(N-N) 1051 (d) RMN 1H (400 MHz, dmso-d6) δ 11.51 (s, 2H), 9.95 (s,1H), 8.51 (d, J = 4.7 Hz, 2H), 8.37 (s, 2H), 7.80 (d, J = 7.8 Hz, 2H), 6.98 (t, J = 7.7 Hz, 1H), 3.02 (s, 6H). RMN 13C (400 MHz, DMSO-d6): δ/ppm, 178.50 (C=S), 155.40 (C-O), 141.59 (C=N), 130.78–120.73(C-Ar), 31.80 (CH3).
Crystallographic Data
H3LMe·CH3OH: C12H16N6OS2; MW: 356.47 g·mol−1; crystal dimensions: 0.12 × 0.03 × 0.02 mm; monoclinic; P21/c; a = 13.2462 (7), b = 19.1436 (9), c = 6.8852 (4) Å; α = 90; β = 99.102(4), γ = 90 0; V = 1723.96(16) Å3; z = 2; μ = 2.96 mm−1; measured reflections = 28545; independent reflections [Rint] = 3149 [0.165]; R = 0.078; wR = 0.191.
3. Results and Discussion
The bisthiosemicarbazone ligand H3LMe can be described as bicompartmental, potentially trianionic, and pentadentate [N2S2O], showing two [NS] binding domains separated by a short spacer with an oxygen donor atom. The ligand H3LMe was fully characterized by the usual techniques for organic compounds.
3.1. IR Spectroscopy
Infrared spectra were obtained in the solid state using the KBr pellet transmission technique in the range 4000–500 cm
−1 (
Figure 2). Band assignments were carried out based on the literature [
6].
In these spectra, the absence of the band corresponding to the carbonyl group, υ(C=O) of the precursor 2-hydroxyisophthalaldehyde around 1700 cm−1, and the appearance of new bands around 1610 cm−1 attributed to the imine υ(C=N) bonds, confirming the formation of the ligand H3LMe, should be highlighted.
3.2. X-ray Diffraction
The recrystallization in methanol of solid H
3L
Me allowed us to obtain yellow crystals suitable for X-ray diffraction studies. The asymmetric unit of the H
3L
Me ligand consists of a ligand molecule solvated by a methanol molecule (
Figure 3). The main bond distances and angles given in
Table 1 and
Table 2 are in the expected range for
bisthiosemicarbazone ligands [
7].
The ligand shows an
E configuration with respect to the imine bonds and an
anti conformation with both branches arranged on opposite sides. This arrangement is conditioned by the existence of intramolecular hydrogen bonds between the imine nitrogen and the hydroxyl group of the spacer. In addition, there are intramolecular hydrogen bonds between the phenolic hydrogen and the oxygen of the solvating molecule, as well as between the thioamide NH and the methanol oxygen atom, and between the OH group of the solvation molecule and the thioamide sulfur of an adjacent ligand. These interactions result in the ligand molecules being connected throughout the crystal lattice (
Figure 4).
4. Conclusions
The new bisthiosemicarbazone ligand H3LMe has been synthesized and isolated with high purity and yield. The X-ray diffraction study of the crystals that were obtained allowed us to know the structure of the ligand. The crystallographic studies revealed that the [NS] donor atoms are oriented in different directions in both ligand branches, indicating a conformational rotation to obtain metal-derived complexes.
Author Contributions
Conceptualization, S.F.-F., L.R.-S. and R.P.; methodology, I.V.-H., S.F.-F., L.R.-S. and R.P.; formal analysis, I.V.-H., S.F.-F. and U.B.-S.; investigation, I.V.-H., S.F.-F., U.B.-S., L.R.-S. and R.P.; resources R.P.; data curation, I.V.-H., S.F.-F., U.B.-S., L.R.-S. and R.P.; writing—original draft preparation, I.V.-H., S.F.-F. and R.P.; writing—review and editing, I.V.-H., S.F.-F., U.B.-S., L.R.-S. and R.P.; supervision, L.R.-S. and R.P.; project administration, L.R.-S. and R.P.; funding acquisition, R.P. All authors have read and agreed to the published version of the manuscript.
Funding
This research was funded by the following FEDER co-funded grants. From Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, 2018GRCGI-1584 (ED431C2018/13), MetalBIONetwork (ED431D2017/01). From Ministerio de Ciencia e Innovación, Project PID2021-127531NB-I00 (AEI/10.13039/501100011033/FEDER, UE) and METALBIO (RED2022-134091-T).
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
The data presented in this study are available in the article.
Conflicts of Interest
The authors declare no conflict of interest.
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