Cancer continues to be a major global health concern and a leading cause of death worldwide. Over the past few decades, the incidence of cancer has steadily increased, with projections estimating that the number of cases will rise from 19.3 million to 28.4 million by 2040 [1,2]. Patients receive tailored therapies such as surgery, chemotherapy, immunotherapy, and radiotherapy based on their cancer type and stage. Chemotherapy, using one or more drugs, has proven effective, but there is a need for new agents that can improve outcomes without harming healthy cells. A notable example is cisplatin, nonetheless, challenges like drug resistance, side effects and ineffective delivery to target sites persist [[3], [4], [5], [6], [7]].

Organotin(IV) carboxylates, represented as R4-nSn(OOCR′)n (where R, R′ are alkyl or aryl group), are a class of compounds that are formed through the coordination of organotin(IV) species with a variety of carboxylic/benzoic acids. They attain unique stereo electronic configuration leading to the chemical diversity and versatility of tin complexes considering factors like oxidation state, ligand type and number, and coordination geometry. As a result, various organotin complexes have been developed, demonstrating a broad spectrum of applications in catalysis, materials science, biomedicine, optoelectronics, memory devices, photoluminescence, semiconductors, solar cells and dyes in cancer cell detection [[8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21]]. In the cancer arena, organotins are easily accessible, less toxic than platinum-based drugs, effective at lower doses, which helps reduce resistance and often demonstrate higher activity than cisplatin. This presents an opportunity to develop novel metallopharmaceuticals that can address some of the limitations of current cancer treatments [[22], [23], [24], [25]]. Among non‑platinum organometallic chemotherapeutics, tri- and di-organotin compounds, especially carboxylates/benzoates, show promise as anticancer agents against tumor cells compared to currently approved drugs [[26], [27], [28]]. The biological efficiency of organotin(IV) compounds is influenced by the nature of the R group and the ligand (L), typically following this order: R3SnL > R2SnL2 > RSnL3 > R4Sn (R = alkyl or aryl, L = mono-anionic ligand) [23,29]. Accordingly, several triphenyltin salicylates were synthesized [[30], [31], [32]] and tested against human breast cancer (MCF-7) and colon cancer (WiDr) cell lines, yielding results comparable to mitomycin C [32]. The coordination ability of 5-[(E)-2-(aryl)-1-diazenyl]-2-hydroxybenzoic acid with triorganotin(IV) centers is now established. In the solid state, the trimethyltin complex [Me3Sn(HL4-Me)]n forms a one-dimensional polymer with benzoate ligands bridging adjacent Sn centers. The Sn atom adopts a trigonal bipyramidal geometry, with methyl ligands in the equatorial plane and an O atom from a benzoate and a hydroxy O atom from an adjacent ligand in the axial positions. In contrast, the triethyltin complex [Et3Sn(HL4-Me)(OH2)] exists as a monomer, featuring a slightly distorted trigonal bipyramidal coordination, with three ethyl ligands in equatorial positions and an O atom from water and a benzoate O atom in the axial positions [33]. Both tribenzyltin [Bz3Sn(HL4-Me)] and triphenyltin [Ph3Sn(HL4-Me)] complexes exhibit distorted tetrahedral geometries [33,34]. In all of the above complexes, HL4-Me refers to 5-[(E)-2-(4-methylphenyl)-1-diazenyl]-2-hydroxybenzoates. Five additional triphenyltin(IV) based complexes also exhibit four-coordinate Sn atoms with a similar distorted tetrahedral geometry, using analogues of the ligand with HL2-Me, HL3-Me, HL4-OMe and HL4-Cl substitutions [35,36]. Recently, triphenyltin 5-[(E)-2-(4-fluorophenyl)-1-diazenyl]-2-hydroxybenzoate, [Ph3Sn(HL4-F)] was synthesized, tested in vitro against prostate cancer cells (DU-145 cell line) and demonstrated strong activity (IC50 value of 1.99 ± 0.18 μM) [37].

Given the synthetic and structural significance, along with the potential biological activity of triphenyltin(IV) complex [Ph3Sn(HL4-F)] [37], it is crucial to further investigate the chemistry of triphenyltin 5-[(E)-2-(aryl)-1-diazenyl]-2-hydroxybenzoates, particularly with increased fluorine substitution in the diazo-formed aryl moiety. In this paper, we present the synthesis, spectroscopic analysis, and crystal structures of three [Ph3Sn(HL3)] (3), [Ph3Sn(HL4)] (4) and [Ph3Sn(HL5)] (5) complexes with varying fluoro-substituted ligands: H′HL3 (2-CF3), H′HL4 (3-CF3) and H′HL5 (4-CF3), while the Ph3Sn moiety is held constant. Additionally, the crystal structure of H′HL5 is reported. For convenience of discussion and comparison, relevant data on structurally characterized triphenyltin 5-[(E)-2-(phenyl)-1-diazenyl]-2-hydroxybenzoate [Ph3Sn(HL1)] 1 (with no fluorine) and triphenyltin 5-[(E)-2-(4-fluorophenyl)-1-diazenyl]-2-hydroxybenzoate [Ph3Sn(HL2)] 2 (with one fluorine atom) have been included.

The in vitro antiproliferative activity of the triphenyltin(IV) 2-hydroxy-5-(phenyldiazenyl)benzoates 1–5 was evaluated against MCF-7 (human breast cancer), HeLa (human cervical cancer), and HEK-293 (normal human embryonic kidney) cells using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. The mechanism of action of the novel triphenyltin(IV) compound [Ph3Sn(L4H)] 4 on MCF-7 cells was evaluated through various experiments involving dichlorodihydro-fluorescein diacetate (DCFH-DA), acridine orange and ethidium bromide (AO/EB), along with assessments of mitochondrial dynamics and distribution. Flow cytometry was also utilized to explore the mechanisms behind the drug-induced cytotoxicity. To assess the influence of fluorine in compounds 3–5, the results were compared with those of the non-fluorinated analog 1 and a 4-fluoro compound 2.