**1. Introduction**

Polyhedral oligomeric silsesquioxanes (SQs) are a large family of compounds that feature diverse structures with Si-O-Si linkages and tetrahedral Si vertices—i.e., random, amorphous, ladder, and cage-like—and the architecture of the latter has attracted considerable scientific interest. It is due to the presence of the inorganic, rigid core (thermal stability, chemical resistance) and organic moieties attached to it (tunable processability) which is the essence of hybrid materials. Functionalized SQs derivatives may be regarded as their nanosized, smallest fragments and precursors that affect and drive the directions of their potential applications [1–6]. Significant development of catalytic protocols for effective and selective anchoring of respective organic functionality to the SQs core has been observed during the last years. The crucial aspect of this is the presence of a proper prefunctional moiety at the Si-O-Si framework, enabling its modification, e.g., Si-H, Si-OH, Si–CH=CH2 units, etc. This, in turn, influences the selection of a respective catalytic procedure for this purpose, e.g., hydrosilylation, cross-metathesis, *O*-silylation, Friedel-Crafts, silylative, Heck, Suzuki, or Sonogashira coupling reactions [2,7–20]. Among these methods, the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) may be an alternative but the only route to yield substituted 1,4-triazole ring functionalities regioselectively [21–23]. This

**Citation:** Rzonsowska, M.; Kozakiewicz, K.; Mituła, K.; Duszczak, J.; Kubicki, M.; Dudziec, B. Synthesis of Silsesquioxanes with Substituted Triazole Ring Functionalities and Their Coordination Ability . *Molecules* **2021**, *26*, 439. https://doi.org/10.3390/ molecules26020439

Academic Editors: Sławomir Rubinsztajn, Marek Cypryk and Wlodzimierz Stanczyk Received: 21 December 2020 Accepted: 12 January 2021 Published:15January2021

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is a powerful synthetic tool to build covalent connections between dissimilar units, and since its discovery in 2002 (independently by Sharpless, Fokin, and Meldal groups), it is widely utilized in (bio-)organic, medicinal and for some time now, also in surface/materials chemistry [24–27]. Despite the simplicity of the reaction, the immense development in the catalyst design, incl. stabilizing ligands, has be observed in the past few years. This may be visible in the aspect of functional group diversity in both reagents and their resilience to the CuAAC reaction conditions, i.e., solvent type, temperature, time, etc. The variety of Cu-based catalysts for this process requires the presence of the Cu(I) species at the highest concentration whether it is introduced in this state or generated in situ [26]. On the other hand, the Cu(I) favors the Glasser coupling of terminal alkynes [28], so the CuAAC conditions should be optimized to avoid the formation of by-products. For this, the in situ creation of Cu(I) ions seems reasonable [24]. As a result of this evolvement, the process gained popularity in the chemistry of silsesquioxanes as well. There are some examples of CuAAC methodology applied for silsesquioxanes to introduce the triazole moiety(-ies) substituted at 1,4 positions with the SQs core and organic group. The process may be applied in the case of mono- and octa-substituted T8 SQs, linked with the Si-O-Si core via mainly alkyl [29–36] but there are also reports on a phenyl group [37,38]. There are also few examples of using di- substituted double-decker (DDSQ) [39,40] or ladder [41] silsesquioxanes [42].

The application of the resulting products with 1,4-triazole ring(s) depends on the kind of alkyne moiety used as a reagent. Due to the interesting photoelectronic properties of SQs-based systems with aryl-triazole groups, they could be possibly used as luminescent materials with enhanced thermal resistance [29,41,43–45]. One of the promising branches of their application is materials chemistry, e.g., as polymers or dendrimers modifiers/synthons [30,39,42,46–54]. They may be also found in macromolecular SQs-based surfactants of amphiphilic and self-assembly or encapsulation properties [31,55,56]. Additionally, the CuAAC methodology serves as a tool for the formation of SQs functionalized peptide dendrimers [35] or glycoconjugates and in targeted bioimaging [57,58].

Catalysis has become a very prospective direction of employing the SQs with 1,4- substituted triazole rings, as catalysts by themselves, e.g., in asymmetric Michael or Aldol reactions [32,33]. Even though there have been still very few reports in this area of interest. One of them reported on the potential coordinating character of a pyridine-triazole moiety attached to the SQs core and revealed its use as a ligand for Pd-complexation. Interestingly, this compound was found to be active in Suzuki–Miyaura cross-coupling [59].

Herein, we present our studies on the copper(I)-catalyzed azide-alkyne cycloaddition process of two different types of silsesquioxanes with the variation of alkynes bearing aryl, hetaryl, alkyl, silyl, siloxyl, or even germyl groups. As a result, we report on the preparation of mono-T8 and difunctionalized double-decker silsesquioxanes with substituted triazole ring(s). The second part of the paper is focused on the application of selected SQs with hetaryl substituted triazole moieties as potential ligands in complexing reaction with transition metals (Pd, Rh, Pt), resulting in the formation of respective SQs-based coordination systems (Figure 1).

**Figure 1.** Mono-T8 and difunctionalized DDSQ silsesquioxanes with Substituted Triazole Ring and the coordinating ability of the pyridine- and thiophenyl-derivatives towards selected TM ions, presented in this work.

#### **2. Results and Discussion**

#### *2.1. The Copper(I)-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) Using* **iBuT8-N3** *and* **DDSQ-2N3**

In the first step, the starting precursors, i.e., the azidopropyl-derivative(s) of mono**iBuT8-N3** and di-**DDSQ-2N3** were prepared in a sequence of hydrolytic condensation of respective silanol precursor of SQs and chlorosilane followed by nucleophilic substitution with NaN3 [60,61] (Figure 2). The idea of the synthetic path is presented below.

**Figure 2.** General route for the synthesis of azide-derivatives **iBuT8-N3** and **DDSQ-2N3**.

The two SQs-based azides **iBuT8-N3** and **DDSQ-2N3** were used as reagents in CuAAC coupling process with a variety of alkynes bearing aryl, alkyl, silyl, and germyl functionalities. The reaction progress was monitored by FT-IR, due to the large mass of the product eliminating the possibility of using GC or GC-MS and confirmed by 1H-NMR. The representative FT-IRs are presented in Figure 3. For all alkynes tested nearly complete conversion of SQs azides was observed within up to 3 days which depended on the type of reaction conditions and Cu catalyst.

**Figure 3.** FT-IR spectra of **iBuT8-N3** and **iBuT8-A1** after completion of CuAAC coupling reaction.

The stacked FT-IR spectra of starting material **iBuT8-N3** and the selected product with 4-pyridine-triazole group **iBuT8-A1** are depicted in Figure 3. The established reaction conditions resulted in the complete conversion of azide (-N=N+=N-) group in **iBuT8-N3**, confirmed by the disappearance of respective bands attributed to stretching asymmetric vibrations of -N=N- at ca. ν¯ = 2098 cm<sup>−</sup><sup>1</sup> (marked in Figure 3). For the CuAAC reaction product, i.e., **iBuT8-A1**, there are new bands in the spectrum, characteristics of C=C, C=N, N=N stretching vibrations from triazole as well as pyridine ring at ca. ¯ν = 1603 cm<sup>−</sup><sup>1</sup> and ν ¯ = 1571 cm<sup>−</sup><sup>1</sup> that confirm the formation of the desired product.

We based on two types of Cu sources, i.e., CuSO4 with sodium ascorbate [40,59] and CuBr with PMDTA [33]. At first, special conditions were created for the reduction of Cu(II) in situ to Cu(I) and then to maintain the introduction of Cu(I) in this oxidation state into the reaction. The main target was to perform the reaction until full conversion of SQ-based azides to avoid the problematic isolation issues of resulting SQ-products with substituted triazole rings(s) from unreacted SQ-based azides. The results of the reactions conducted to obtain products with substituted triazole ring(s) are collected in Table 1 for T8-derivatives and in Table 2 for DDSQ-derivatives.

**Table 1.** Copper-catalyzed azide-alkyne cycloaddition using **iBuT8-N3** and alkynes.

a Reaction conditions for Cu(II) source: [azide]:[alkyne]:[CuSO4][sodium ascorbate] = 1:1.4–8:0.025–0.25:0.3–5; 25–60 ◦C; 72–96 h. b Reaction conditions for Cu(I) source: [azide]:[alkyne]:[CuBr][PMDTA] = 1:1.45:0.1:0.1; 25 ◦C; 24 h. c additional 12 h at 45 ◦C. > 99% conversion of **iBuT8-N3** was confirmed by FT-IR in situ and 1H-NMR analyses. Value in parenthesis is given for isolation yield (%).

a Reaction conditions for Cu(II) source: [azide]:[alkyne]:[CuSO4][sodium ascorbate] = 1:1.4–8:0.025–0.25:0.3–5; 25–60 ◦C; 72–96 h. > 99% conversion of **DDSQ-2N3** was confirmed by FT-IR in situ and 1H-NMR analyses. Value in parenthesis is given for isolation yield (%).

The results of DDSQ-based systems with substituted triazole rings are collected in Table 2 and involves the selective formation of DDSQ-compounds with the two abovementioned triazole moieties. The spectrum of used alkynes varies as they contain aryl,

hetaryl, alkyl, and silyl derivatives of commercial availability. Additionally, we tested ethynyl(triethyl)germane (A9) and ethynylsiloxysubstituted-iBuT8 (A8) to verify their potential in the CuAAC process.

The tested reaction conditions based on Cu(II) and Cu(I) catalysts seem to be analogous in the case of less demanding alkynes, i.e., simple aryl or alkyl derivatives. Interestingly, for the 5-hexynenitrile, the applied catalytic conditions did not affect the present -CN moiety that in general may also be reactive and susceptible to alkyne-azide coupling reaction conditions to form respective 5-substituted tetrazoles [62]. For this, the presence of a reactive -CN moiety could be used in further modifications of the obtained products: **iBuT8-A4** and **DDSQ-2A4**. The reactivity of ethynylsilane (A9), ethynylgermane (A10) and also ethynylsiloxysubstituted iBuT8 (A8) compounds was tested with positive results. However, the use of silyl (A9) or germyl (A10) alkyne proceeded with >99% conversion of SQs-based azides (**iBuT8-N3** and **DDSQ-2N3**) only when modified reaction conditions with Cu(I) [33] were applied (heating at 45 ◦C). Even though, for ethynylsiloxysubstitutediBuT8 (A8) up to 10% of unreacted **iBuT8-N3** was observed. It could be separated from the resulting product **iBuT8-A8** during the purification with the use of chromatography column and proper eluent selection (hexane:DCM 3:1 for separation of **iBuT8-N3** from **iBuT8-A8**). Lower reactivity of A8 may derive from the presence of oxygen as the silicon atom in the vicinity of ethynyl-moiety and its electron-withdrawing impact. It should be noted that ethynylsilanes exhibit reactivity in this process, but conditions created by us seem to be milder for lower reaction temperature [63]. On the other hand, it would be the first example for ethynylgermane (A10) to exhibit high reactivity in the CuAAC reaction. One report on the formation of 4-germyl-substituted triazole ring derivative concerns using internal alkyne, i.e., 3-(trimethylgermyl)-2-propynal [64]. Additionally, the reports on the reactivity of the ethynylsiloxy-moiety (meaning A8) in the CuAAC process are very scarce [65].

An interesting relationship was found for 1H-NMR analyses of DDSQs bearing triazole ring substituted at 4-positition with an aryl (**DDSQ-2A1**) and alkyl (**DDSQ-2A4**) group. The resonance line of a very significant triazole proton N=C-H<sup>t</sup> at 5*H*-position of triazole ring depends on the type of the moiety at 4-position of the latter. The crucial aspect may be its electronic property and the respective shielding effect of alkyl and deshielding effect characteristic for the aryl moiety presence. It affects the N=C-H<sup>t</sup> signal shift and it is upfield for **DDSQ-2A1** to be present at 6.75 ppm and downfield for **DDSQ-2A4**, to appear at 7.84 ppm, which gives a total change in resonance lines of 1.09 ppm (Figure 4). Due to the presence of a triazole, aromatic ring, this effect is also insensibly perceptible for -CH2- group at 1*N*-position of this ring (for **DDSQ-2A1** δ = 4.15 ppm and **DDSQ-2A4** δ = 4.21 ppm) (Figure 4). This is a notable difference in chemical shifts of N=C-H<sup>t</sup> at triazole ring for its alkyl and aryl derivatives when compared with analogous compounds of iBu-SQs, i.e., **iBuT8-A4** (alkyl δ = 7.31 ppm) and **iBuT8-A1** (aryl δ = 8.12 ppm) that equals 0.82 ppm (Figure 5). It is even more significant when comparing analogous products with alkyl groups at triazole ring but with diverse Si-O-Si cores, i.e., **DDSQ-2A4**, N=C-H<sup>t</sup> proton present at 6.75 ppm with **iBuT8-A4**, =C-H<sup>t</sup> at 7.31 ppm. These differences in result may be explained by the presence and electronic effect of the DDSQ core with phenyl substituents.

**Figure 4.** Selected range of stacked 1H-NMR spectra of **DDSQ-2A1** and **DDSQ-2A4**.

**Figure 5.** Selected range of stacked 1H-NMR spectra of **iBuT8-A1** and **iBuT8-A4**.

#### *2.2. X-ray Analysis of* **DDSQ-2A1**

A DDSQ-based pyridine-triazole derivative, i.e., **DDSQ-2A1** proved to be a solid and acquired the form of crystals amenable to X-ray crystal structure determination (Figure 6). The molecule is *Ci*-symmetrical, as it lies across the center of inversion in the space group *P21/c*. The structure of the core may be described as built of four rings, two 8-membered (four Si, four O), and two 10-membered (five Si, five O), which can be noted as 82102. The geometry of the core of the molecule is determined by two factors: one rigid—Si-O distance, which has a very narrow spread (mean value 1.615(8) Å), and one flexible Si-O-Si angles (140.77(16)◦–162.43(16)◦). Similar tendencies were noted in similar molecules [16,66]. The architecture of the crystal is determined by weak but numerous interactions (C-H···O, C-H···π, π···π etc.). These multiple interactions give rise to quite significant interaction energies. Calculations with PIXEL method give results as high as −160.5, −95.7, and −85.4 kJ/mol for the three highest interaction energies between molecules, and −555.5 kJ/mol as total packing energy [67,68].

All of the T8 and DDSQ-based compounds with substituted triazole ring(s) were isolated in high, up to 90% yields. They are air-stable white or light-yellow solids with good solubility in DCM, CHCl3, THF, toluene. The solubility in MeOH, MeCN and for hexane depends on the type of SQ's core, i.e., **iBuT8** derivatives are more soluble than **DDSQ**s.

**Figure 6.** A perspective view of the molecule. Ellipsoids are drawn at the 50% probability level, hydrogen atoms are shown as spheres of arbitrary radii (grey-C, white-H, blue-N, red-O, yellow-Si).

*2.3. SQs-Based Pyridyl- and Thiophenyl-Triazole Derivatives (***iBuT8-A1**, **DDSQ-2A1**, **iBuT8-A7***) as Bidentate Ligands in the Formation of Coordination Complexes with Selected Transition Metals (TM = Pd, Pt, Rh)*

The next step was to verify the coordination properties of selected T8 and DDSQ products type possessing heteroatom at 4*C* triazole ring, i.e., N (**iBuT8-A1**, **DDSQ-2A1**) and S (**iBuT8-A7**). Using 2-ethynylpyridine and 2-ethynylthiophene derivatives created the possibility to form bidentate ligands of NˆN and NˆS kind donation. For this purpose, we chose TM metals that are known to form coordination compounds with SQs-based ligands, i.e., Pd(II) [59,69], Rh(I) [70], and Pt(II) [71].The general scheme for using T8-type ligands, i.e., **iBuT8-A1** and **iBuT8-A7** is disclosed in Figure 7 for Pd(II), Pt(II), and Rh(I) and DDSQ-based ligand with Pd(II) in Figure 8.

**Figure 7.** General procedure for the synthesis of T8-based NˆN and NˆS type mononuclear coordination compounds with Pd(II) (**iBuT8-A7-Pt(NˆS)**), Pt(II) (**iBuT8-A1-Pt(NˆN)**), and binuclear with Rh(I) ((**iBuT8-A1)2-Rh(NˆN)**).

**Figure 8.** General procedure for the synthesis of DDSQ-based NˆN coordination compound with Pd(II) (**DDSQ-A1-[Pd(NˆN)]2**).

The analogous verification was performed in terms of **DDSQ-2A1** possessing bidentate NˆN ligand Pd(II). The 1:2 (ligand: metal) stoichiometry of the reaction enabled the formation of a molecular system with two Pd(II) ions captured to the opposite parts of the DDSQ core (Figure 8).

To our knowledge, this is the first example of the DDSQ-based molecular complex possessing a bidentate pyridine-triazole ligand with coordination TM Pd(II) ion. Furthermore, it is an interesting example of using difunctionalized DDSQ compounds to anchor metal ions and the reports on these systems have been still profoundly limited [71,72].

For the reaction aiming at palladium and rhodium complexes, their cyclooctadiene precursors were used and for platinum, the tetrachloroplatinate(II) was applied. The mononuclear compounds **iBuT8-A7-Pt(NˆS)** and **iBuT8-A1-Pt(NˆN)** are air-stable, pale yellow solids. The dinuclear Rh(I) based complex ((**iBuT8-A1)2-Rh(NˆN)**) is rather an airand moisture sensitive orange solid and its synthesis was performed with the use of the Schlenk technique. The iBuT8-derivatives are soluble in DCM, CHCl3, THF, toluene, and of very low solubility in methanol. The DDSQ-based Pd(II) complex **DDSQ-A1-[Pd(NˆN)]2** is an air-stable pale yellow solid with very limited solubility in DCM, CHCl3, and THF and soluble in DMF and DMSO. The four coordination SQ-based compounds were isolated in yields 55%–93% and characterized using spectroscopic analysis proving their formation (for details see ESI). The respective comparison of the 1H-NMR stacked spectra of ligand **DDSQ-A1** and respective complex **DDSQ-A1-[Pd(NˆN)]2** are presented below (Figure 9).

**Figure 9.** Selected range of stacked 1H-NMR spectra of **DDSQ-A1** and **DDSQ-A1-[Pd(NˆN)]2**.

The presence of Pd with its chloro-ligands in **DDSQ-A1-[Pd(NˆN)]2** affects the polarity of the complex and restricts its solubility in a common, less polar solvent and for this reason DMF-*d*7 was selected in order to compare 1H-NMR spectra. As expected from the results obtained for the iBuT8-based Pd, Pt, and Rh complexes and from the literature reports [59], the placement of resonance line of the triazole proton N=C-H<sup>t</sup> is susceptible to the chemical surrounding and presence of a different type of TM ion. However, in general, in each complex its shift is downfield significantly. For **DDSQ-A1-[Pd(NˆN)]2** N=C-H<sup>t</sup> there is a notable difference in its chemical shift to appear at δ = 9.18 ppm when compared with a bare ligand, i.e., **DDSQ-A1**: N=C-H<sup>t</sup> at δ = 8.53 ppm (Figure 9). Additionally, the resonance lines derived from the pyridine ring are also shifted downfield due to the changes in the electron density on the hetaryl moiety while coordinating to Pd ion, especially for the =C-H5.

#### **3. Materials and Methods**

### *3.1. Materials*

The chemicals were purchased from the following sources: Hybrid Plastics (Hybrid Plastics, Hattiesburg, MS, USA) for DDSQ tetrasilanol form (C48H44O14Si8) (DDSQ-4OH), trisilanol (C28H66O12Si7)(iBuT8-3OH); Sigma-Aldrich (Saint Louis, MO, USA) for: dichloromethane (DCM), tetrahydrofuran (THF), dimethylformamide (DMF), toluene, methanol, acetonitrile (MeCN), chloroform (CHCl3), hexane, chloroform-*d*, dimethyl sulfoxide-*d*6 (DMSO-*d*6), dichloromethane-*d*2 (DCM-*d*2), (dimethylphenylsilyl)acetylene, 2-ethynylpyridine, *<sup>N</sup>*-methyl-*<sup>N</sup>*-propargylbenzylamine, 3-butynylbenzene, phenylacetylene, n-heptyne, 1,4-diethynylbenzene, 5-hexynenitrile, 2-ethynylthiophene; ABCR (ABCR, Karlsruhe, Germany) for dichloro(3-chloropropyl)methylsilane, molecular sieves, triethylamine, and silica gel 60. Chemat (Gdansk, Poland) for: sodium L-ascorbate crystalline, ammonium chloride, copper(II) sulfate pentahydrate, copper(I) bromide, *N*,*N*,*N*,*N*,*N*- pentamethyldiethylenetriamine (PMDTA), sodium azide, sodium sulfate anhydrous, dichloro(1,5-cyclooctadiene)palladium(II), chloro(1,5-cyclooctadiene)rhodium(I) dimer, potassium tetrachloroplatinate(II). Tetrahydrofuran (THF) was refluxed over sodium/ benzophenone and distilled. Triethylamine (Et3N) was distilled over calcium hydride before use. DMF was stored under argon. Ethynyl(triethyl)germane (A10) and ethynyl (dimethylsiloxy)hepta(i-butyl)octasilsesquioxane (A8) was synthesized according to the

literature procedures [73,74]. (3-chloropropyl)hepta(i-butyl)octasilsesquioxane (iBuT8-Cl) and DDSQ-2Cl were obtained via corner- and side-capping hydrolytic condensation procedure, and mono- and diazido-functionalized silsesquioxanes (**iBuT8-N3**, **DDSQ-2N3**) were synthesized via nucleophilic substitution according to the literature procedures [60,61]. All syntheses were conducted under argon atmosphere using standard Schlenk-line and vacuum techniques.
