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Article

Dibromo–Isonitrile and N-acyclic Carbene Complexes of Platinum(II): Synthesis and Reactivity

by
Anna Farasat
1,
Francesca Nerli
1,
Luca Labella
1,2,3,
Marco Taddei
1,2 and
Simona Samaritani
1,2,3,*
1
Department of Chemistry and Industrial Chemistry, University of Pisa, Via Giuseppe Moruzzi 13, 56124 Pisa, Italy
2
CISUP—Center for the Integration of Scientific Instruments, University of Pisa, 56126 Pisa, Italy
3
Interuniversity Consortium for the Research on the Chemistry of Metals in Biological Systems (CIRCMSB), 70126 Bari, Italy
*
Author to whom correspondence should be addressed.
Inorganics 2023, 11(4), 137; https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics11040137
Submission received: 2 March 2023 / Revised: 17 March 2023 / Accepted: 21 March 2023 / Published: 23 March 2023
(This article belongs to the Special Issue Phosphorus Ligands for the Stabilization of Unusual and Elusive Structures in Transition Metal Complexes)
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Abstract

:
A series of dibromo-N-acyclic (NAC) carbene complexes of platinum(II) were synthesized, starting from trans-[Pt(μ-Br)Br(PPh3)]2 and according to a protocol previously optimized for the preparation of analogous chlorinated compounds. In the first step of the synthesis, the ring opening of the dinuclear precursor was carried out using suitable isonitrile ligands, while the following step consisted of the addition of N,N-diethylamine to the products obtained in the first step. The two reactions were separately investigated, and attention was given to the differences between brominated and chlorinated systems.

Graphical Abstract

1. Introduction

In the context of our studies about platinum complexes with antiproliferative properties [1,2,3,4,5,6], we have been searching for new scaffolds to outline compounds capable of circumventing platinum resistance phenomena [7,8]. Among the complexes prepared, those bearing a triphenylphosphino ligand proved capable of affecting mitochondria, and their modes of action often proved effective on cisplatin resistant cell lines. This prompted us to design many [PtCl2(PPh3)(L)] complexes, where the PPh3 ligand was maintained in the coordination sphere of the metal, while neutral ligands L were varied, affording libraries of compounds with modulable biological properties. We have recently prepared systems where L was a N-acyclic carbene (NAC) of platinum(II) [9]. The syntheses were carried out starting from the dinuclear precursor trans-[Pt(μ-Cl)Cl(PPh3)]2 [10], which was reacted with suitable isocyanide (RNC) ligands, affording cis-[PtCl2(PPh3)(CNR)] (R = 4-MeOC6H4, CH2Ph). The isocyanido complex was then reacted with a secondary amine R2NH, to afford the NAC product of addition to the coordinated isonitrile functional group. The reaction was chemoselective towards addition and stereoselective in both steps, since only cis carbene complexes were obtained. It was also shown that when particularly nucleophilic alicyclic amines (pyrrolidine, morpholine and piperidine) were used, ionic products were obtained, arising from the substitution of a chlorido ligand. The obtained derivatives showed a good solubility and stability in dimethylsulfoxide (DMSO) solution; thus, their antiproliferative properties are now under evaluation. In addition to the neutral ligands, the leaving groups as well can play an important role in modulating the properties of anticancer complexes [11,12]. Considering the wide applications described for carbene metal complexes in both bioinorganics [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30] and catalysis [31,32,33,34,35,36,37,38,39,40,41,42,43,44], we hereby describe the synthesis of new [PtBr2(PPh3)(CNR)] and [PtBr2(PPh3)(NAC)] compounds, in order to compare their properties with those of their chlorinated counterparts.

2. Results and Discussion

2.1. Synthesis of Isocyanide Complexes [PtBr2(PPh3)(CNR)]

The preparation of isonitrile derivatives [PtBr2(PPh3)(CNR)] was carried out according to the reaction depicted in Scheme 1. The dinuclear brominated precursor was prepared according to a convenient reported procedure, starting from the easily available [PtCl2(NCMe)2] [45] (see Supplementary Material for the synthesis), while the chosen isonitrile ligands were commercially available.
The ring-opening reaction of the dinuclear precursor was carried out in 1,2-dichloroethane (1,2-DCE) and was followed by TLC or 31P nuclear magnetic resonance (NMR) spectroscopy. The isonitrile ([ligand]/[Pt] = 2.0 molar ratio) was dissolved in 1,2-DCE and the addition was made at 0 °C to avoid any further substitution by the nucleophile. In all cases, the initially orange suspension turned into a light yellow, clear solution in a few hours and the chromatographic or spectroscopic analysis evidenced the disappearance of the precursor and the presence of products in solution. Only in the case of tert-butylisocyanide, a [ligand]/[Pt]= 3.0 molar ratio was necessary to obtain the complete conversion of the precursor, occurring anyway within a few hours at room temperature. The reaction is directed by the trans effect exerted by the phosphine ligand, so that the expected kinetic product is trans-[PtBr2(PPh3)(CNR)]. However, being both isonitrile and triphenylphosphine π-acid ligands, the initial formation of the kinetic product can be followed by a fast isomerization process in solution, to afford a mixture of isomers, where the cis complex is the most abundant [9]. Meanwhile, for the analogous chloro-complexes [9], we observed the complete conversion of the kinetic ring-opening products into cis-[PtCl2(PPh3)(CNR)]; in this case, a mixture of the two geometric isomers was obtained in most of the studied cases, both during the reaction and on the isolated samples, most likely for the higher steric hindrance of cis bromide ligands. Isolated yields in cis,trans complexes were quite good and the composition of the equilibrium mixtures could be conveniently studied using 31P NMR spectroscopy.
Isolated yields and percentage compositions at equilibrium in solution are indicated in Table 1. Cis,trans percentages were calculated by integrating the corresponding 31P NMR signals in CDCl3 solution.
The coordination of isonitrile ligands to the platinum center was evidenced in 31P NMR spectra by the presence of satellites, with 1JP-Pt coupling constants within 3310–3380 Hz for both isomers, in agreement with previous results [2,9,45]. In the 195Pt NMR spectra, doublet signals were observed in the −4180–−4600 ppm spectral zone, with the same 1JPPt coupling constants measured in the 31P NMR spectra. In comparing these values with those previously observed for the chlorinated counterparts [9], a shift towards high fields is evident, coherently with the substitution of chlorido ligands with bromido ones [46,47,48,49,50,51,52]. Coordination was evident in the infrared (IR) spectrum as well, where very strong absorption bands were observed around 2200–2240 cm−1, with an hypsochromic shift of about 90–100 cm−1 from the position of the same band in the free ligand [53].
In the case of complex 3, well-shaped single crystals were obtained by slow diffusion of pentane vapors into a chloroform solution of the compound, and the molecular structure was determined using single crystal X-ray diffraction. The structure of 3 is reported in Figure 1, while the most significant bond lengths and angles are listed in Table 2. The compound crystallized in the triclinic P-1 space group, and two independent molecules were observed in the unit cell, together with a molecule of chloroform. The coordination is square planar around the metal and the configuration is cis, with small deviations from ideality. The structure is in very good agreement with that previously described [9] for the chlorinated analogue cis-[PtCl2(CNC6H4(OCH3))(PPh3)], where the most important differences in bond lengths have been ascribed to the larger size of bromido ions.

2.2. Synthesis of Carbene Complexes [PtBr2(PPh3)(Et2N(H)CNR)]

The synthesis of the NAC derivatives was carried out in 1,2-DCE solution, according to an experimental procedure previously applied to the successful preparation of chlorinated models. In each experiment, the chosen isocyanide complex was dissolved in 1,2-DCE and treated with a solution of N,N-diethylamine in the same solvent (Scheme 2) at 0 °C, following the reaction spectroscopically (31P NMR). When complexes one and three were used, the reaction proceeded smoothly to afford the expected NAC product in a good, isolated yield.
The unprecedented 5 and 6 bromocomplexes were spectroscopically characterized. In the attenuated total reflectance IR spectra, the strong absorption band due to the stretching of isonitrile functional group was no longer observable, while a typical absorption band appeared, in both cases, around 1550 cm−1, which could be ascribed to NCN stretching. In the 31P NMR spectra, the disappearance of signals due to the isocyanido precursors was accompanied by the presence of new signals with satellites (JP-Pt ≈ 4000 Hz), which could be ascribed to the carbene species. In the case of benzyl derivative 5, a single signal was observed both in 31P- and 195Pt NMR spectra, indicating the stereoselectivity of the process towards the formation of a single isomer, to which a cis geometry was assigned for analogy with the analogous chlorinated system [9]. In the case of the 4-methoxyphenyl derivative 6, a mixture of carbene products was observed, as indicated by the presence of two distinct signals with satellites in the 31P NMR spectrum and of two doublet signals in the 195Pt NMR one. The equilibrium composition of the mixture was 80/20 and it seems reasonable to assign the cis geometry to the main component of the mixture, taking into account the complete stereoselectivity observed in the synthesis of the analogous chlorinated compound [9]. The 1H NMR spectra of the carbene complexes 5 and 6 were quite typical of rigid systems, with non-equivalent hydrogen atoms affording distinct signals. As an example, we report the 1H NMR spectrum of complex 5 (Figure 2).
In the aliphatic portion of the spectrum, benzyl hydrogen atoms Ha and Hb originate two distinct double doublet signals at 5.65 and 4.44 ppm, where a typical geminal coupling constant (12 Hz) can be measured. Analogously, each of the four methylene hydrogen atoms of the diethylamino moiety (Hd-g) gives rise to a distinct multiplet signal (at 4.79, 3.64, 2.85 and 2.80 ppm). Finally, two triplet signals are observable at 1.19 and 0.88 ppm, which can be attributed to the two methyl groups of the diethylamino residue. The non-equivalence of the ethyl groups of the diethylamino residue is well observable in the 13C NMR spectrum as well, where each carbon atom originates a distinct signal. A very similar spectral profile, although complicated by the presence of two geometric isomers, was observed in the NMR spectra of complex 6.
The reaction of tert-butylisocyano derivative 2 with N,N-diethylamine did not afford the expected products. Indeed, 31P NMR analyses carried out on samples of the reaction mixture at different time spans revealed only the presence of the precursor. A greater excess of the nucleophile was added and the mixture was refluxed longer; nonetheless, the composition of the solution did not change and the precursor was recovered after the usual work-up procedures. It seems reasonable to ascribe this different behavior to the steric hindrance of the tert-butyl group. As a matter of fact, a sample of cis-[PtCl2(PPh3)(CNtert-Bu)], prepared in this work (see Supplementary Material for the synthesis) showed the same reactivity as the bromo complex.
Attempts were made to prepare the diethylamino NAC carbene of functionalized isocyano derivative 4. Unfortunately, repeated experiments afforded complex mixtures that could not be purified. It has to be noted that 4 is characterized by the presence of enolizable hydrogen atoms, in alfa position to diethyl carboxylate group. Indeed, this ligand is a synthetic equivalent of glycine and it has been used successfully to synthesize complex aminoacidic derivatives in experimental procedures based mostly upon the acidity of hydrogen atoms in alfa position to the ester group [54]. It is likely that, in the presence of N,N-diethylamine, enolization equilibria are established, leading to the formation of byproducts. The same behavior was observed when a sample of cis-[PtCl2(PPh3)(CNCH2COOEt)] (see Supplementary Material for the synthesis) was reacted with N,N-diethylamine.

2.3. Stability of Complexes in DMSO

As anticipated, one of the possible applications of the prepared carbene complexes concerns their possible activity as anticancer agents. In view of the study of their antiproliferative properties in vitro, the stability of the derivatives in media used for the biological tests is mandatory. The compounds here prepared are not soluble in water or ethanol and are well soluble in DMSO; however, it is well known [55] that the coordination properties of DMSO towards platinum can severely affect the nature of the tested compounds. Indeed, the coordination of this solvent to the metal center can be competitive with certain ligands, displacing them or, in the presence of traces of water, assisting metal-halogen hydrolysis processes [56,57]. The occurrence of these side reactions is often enhanced by the presence of strongly trans-directing ligands. Thus, the behavior of derivatives 1–6 in DMSO was studied spectroscopically. In particular, the stability of the complexes was conveniently checked by 31P NMR, as the possible substitution product of the isonitrile or NAC ligand by DMSO (cis-[PtBr2(PPh3)(SOMe2)]) is known to afford a signal at 17.2 ppm in d6-DMSO (1JP-Pt = 3730 Hz) [45]. In a typical experiment, a sample of the NAC complex 5 (about 10 mg) was dissolved in d6-DMSO and analyzed at different time spans (t = 0, 24 and 72 h). A single signal was observed in the freshly prepared sample (8.59 ppm, 1JP-Pt = 4084 Hz, Figure S1), well in agreement with the 31P NMR characterization previously registered in CDCl3. Analogously, in the 1H NMR, all the signals attributed to 5 were present (Figure S2). No changes were observed in the spectra registered on the same sample after 24 and 72 h (Figures S3–S6). Other complexes afforded analogous results, thus proving their stability in DMSO.

3. Conclusions

The synthetic protocol previously used for the preparation of [PtCl2(PPh3)(CNR)] and [PtCl2(PPh3)(NAC)] derivatives proved suitable for the synthesis of the analogous brominated systems. Starting from trans-[Pt(μ-Br)Br(PPh3)]2, the corresponding isonitrile complexes [PtBr2(PPh3)(CNR)] (R = Bz (1), tert-Bu (2), 4-MeOC6H4 (3) and CH2COOEt (4)) were obtained with very good yields (75–98%), although the reaction was not as stereoselective as for the chlorinated counterparts and mixtures of geometric isomers, generally enriched in the cis isomer, were observed in chloroform solution. This behavior can be reasonably ascribed to the steric hindrance of bromido ligands. In the case of R = 4-MeOC6H4 (3), the cis isomer was crystallized, and its molecular structure was determined using single crystal X-ray diffraction. The reaction of the isonitrile derivatives 1 and 3 with N,N-diethylamine afforded the desired NAC compounds in good yields (69–87%), while the reaction failed when substrates 2 and 4 were used. In the case of complex 2, the complete lack of reactivity observed seems to have been caused by the steric hindrance exerted by the tert-butyl residue on the isonitrile functional group, which makes it scarcely accessible by the attacking N,N-diethylamine. As for complex 4, it is reasonable to ascribe the side reactions observed to the high reactivity of hydrogen atoms in alfa position to the ethyl carboxylate group in a basic environment. Indeed, the easily enolizable hydrogen atoms of ethyl-2-isocyanoacetate are commonly exploited to synthetize glycine derivatives [54]. Finally, both isonitrile and NAC complexes proved stable in DMSO solution, where they are all well soluble; thus, their antiproliferative properties will be investigated in vitro and compared with their chlorido counterparts.

4. Materials and Methods

General. All manipulations were carried out under inert (Ar) atmosphere, if not otherwise stated. Usual procedures were followed to purify and dry solvents [58,59]. Solid, commercially available reagents were used with no further purification. Samples of [PtBr2(NCMe)2] [45], trans-[Pt(μ-Br)Br(PPh3)]2 [45], trans-[Pt(μ-Cl)Cl(PPh3)]2 [10] were prepared according to reported procedures. Samples of 4-methoxyphenylisocyanide, benzylisocyanide, tert-butylisocyanide and ethyl isocyanoacetate were purchased from ™Merck and used without further purification. N,N-diethylamine was distilled over KOH and filtered over dry alumina immediately before use. An elemental analyzer “Vario MICRO CUBE” CHNOS was used for elemental analysis. IR spectra were recorded on an Agilent “Cary 630” spectrometer, equipped with an ATR accessory; absorption peak ( ν ˜ , cm−1) intensities and shapes were described by the following abbreviations: s = strong, m = medium, w = weak, br = broad and sh = shoulder. 1H-, 13C-, 31P- and 195Pt NMR spectra were recorded on JEOL YH 400 MHz and JEOL CZR 500 MHz spectrometers, in CDCl3 solution (™Deutero GmbH, stored over Ag) if not otherwise stated. When samples of the reaction mixtures were analyzed using 31P NMR in non-deuterated solvents, a sealed capillary containing C6D6 was inserted into the sample to lock the instrument. Chemical shifts (δ ppm) referred to: Si(CH3)4 for 1H and 13C, H3PO4 (85% in D2O) for 31P and H2PtCl6 for 195Pt. The observed signals were described according to the following abbreviations: s = singlet, d = doublet, t = triplet, dd = doublet of doublets, q = quadruplet and m = multiplet.

4.1. General Procedure for the Synthesis of [PtBr2(PPh3)(CNR)]

In a Schlenk tube equipped with a magnetic stirrer, an orange suspension of trans-[Pt(μ-Br)Br(PPh3)]2 [45] (0.200–0.400 g) in 1,2-DCE (10–15 mL) was cooled (0 °C) and treated, under stirring, with a solution of the suitable isocyanide in the same solvent ([isocyanide]/[Pt] = 2.0 molar ratio). The temperature was raised (25 °C) and a clear, light yellow solution was obtained (2–12 h). The proceeding of the reaction was checked by TLC and/or 31P NMR. The mixture was stirred until the maximum conversion of the precursor was obtained; then, the solution was concentrated under a vacuum up to a quarter of the original volume and treated with n-heptane (20–30 mL). A waxy–oily solid precipitated, which turned into a colorless powder upon prolonged stirring (3–12 h). The product was filtered, washed with n-heptane (2 × 3 mL) and dried under a vacuum. For each complex, the used isocyanide ligand, the yield, the elemental analysis and the spectroscopic (IR and NMR) characterizations are reported.
Cis,trans-[PtBr2(CNCH2Ph)(PPh3)] (1). Benzylisocyanide, 0.293 g (93%). NMR analysis showed the presence of two geometric cis,trans isomers in a 41/59 molar ratio.
El. Anal. Calcd C26H22 Br2NPPt, %: C 42.5, H 3.0 and N 1.9. Found, %: C 42.2, H 3.2 and N 2.2.
IR (ATR, ν ˜ , cm−1): 3053 w, 2957 w, 2933 w, 2919 w, 2234 s (stretching C≡N), 2146 m, 1964 w, 1896 w, 1816 w, 1670 w, 1603 w, 1480 m, 1435 s, 1345 w, 1310 w, 1230 w, 1182 w, 1160 w, 1099 s, 999 w, 739 s and 691 s.
1H NMR (mixture of isomers): 7.75–7.07 (m, Harom), 4.42(s, CH2, 41%) and 4.31(s, CH2, 59%).
31P NMR (mixture of isomers): 9.45 (1JP-Pt = 3330 Hz, 59%) and 7.14 (1JP-Pt = 3310 Hz, 41%).
195Pt NMR (mixture of isomers): −4600(1JP-Pt = 3330Hz, 41%) and −4402 (1JP-Pt =3310Hz, 59%).
Cis,trans-[PtBr2(CNC(CH3)3)(PPh3)] (2). Tert-Butylisocyanide, (tert-Butylisocyanide]/[Pt] = 3.0 molar ratio), 0.384 g (98%). NMR analysis showed the presence of two geometric cis,trans isomers in a 85/15 molar ratio.
El. Anal. Calcd C23H24Br2NPPt·DCE, % C 37.6, H 3.5 and N 1.8. Found, % C 37.6, H 3.2% and N 2.2%.
IR (ATR, ν ˜ , cm−1): 3047 w, 2981 w, 2226 s (stretching C≡N), 2143 w, 1982 w, 1900 w, 1828 w, 1773 w, 1479 m, 1432 s, 1401 w, 1372 m, 1310 m, 1185 s, 1096 s, 995 m, 930 w, 880 w, 75 3s and 693 s.
31P NMR(mixture of isomers): 9.94 (3397 Hz, 15%) and 9.30 (1JP-Pt = 3375 Hz, 85%).
195Pt NMR (mixture of isomers): −4259 1JP-Pt = (1JP-Pt = 3397 Hz, 15%) and −4397 (1JP-Pt = 3375 Hz, 85%).
Cis,trans-[PtBr2(CNC6H4(OCH3))(PPh3)] (3). 4-Methoxyphenylisocyanide, 0.353 g (75%). NMR analysis showed the presence of two geometric cis,trans isomers in a 76/24 molar ratio.
El. Anal. C26H22Br2NOPPt Calcd, % C 41.6, H 3.0, N 1.9. Found, C 42.0, H 3.3 and N 1.8%.
IR (ATR, ν ˜ , cm−1): 3058 w, 3005 w, 2935 w, 2839 w, 2206 s (stretching C≡N), 1991 w, 1889 w, 1815 w, 1761 w, 1673 w, 1600 m, 1503 s, 1433 s, 1301 m, 1252 s, 1165 m, 1099 s, 1024 m, 833 s, 746 s and 691 s.
31P NMR (mixture of isomers): 10.2 (1JP-Pt = 3339 Hz, 24%) and 9.5 (1JP-Pt = 3313 Hz, cis 76%).
195Pt NMR (mixture of isomers): −4187 1JP-Pt = (1JP-Pt = 3339 Hz, 24%) and −4358 (1JP-Pt = 3313 Hz, 76%).
Cis-[PtBr2(CNCH2COOEt)(PPh3)] (4). ethyl isocyanoacetate, 0.246 g, (83%).
El. Anal. C23H22Br2NO2PPt, Calcd, %: C 37.8, H 3.0 and N 1.9. Found, %: C 37.5, H 2.6 and N 2.2.
IR (ATR, ν ˜ , cm−1): 3055 w, 2978 w, 2952 w, 2905 w, 2240 s (stretching C≡N), 1748 s (stretching C꞊O), 1482 m, 1435 m, 1373 w, 1341 w, 1279 w, 1245 w, 1219 s, 1159 w, 1094 s, 1027 m, 994 m, 937 w, 857 w, 748 m, 709 m and 692 s.
1H NMR: 7.8–7.7 (m, 6H, Harom), 7.5–7.4 (m, 9H, Harom), 4.1 (q, J = 7.0 Hz, 2H, COOCH2), 3.9 (s, 2H, 1JPPt = 17 Hz, CH2CO) and 1.28 (t, J = 7.0 Hz, 3H, CH3).
31P NMR: 8.8 (1JPPt = 3300 Hz).
195Pt NMR: −4400 (1JPPt = 3300 Hz).

4.2. General Procedure for the Synthesis of [PtBr2(PPh3)(Et2N(H)CNR)]

In a Schlenk tube equipped with a magnetic stirrer, a solution of the suitable [PtBr2(PPh3)(CNR)] (0.180–0.400 g) in 1,2-DCE (10–15 mL) was cooled (0 °C) and a solution of N,N-diethylamine (Et2NH) in 2 mL of the same solvent ([Et2NH]/[Pt] = 2.0 molar ratio) was added dropwise under stirring over 1 h. The temperature was slowly raised (25 °C) and the solution was stirred for 24 h. The proceeding of the reaction was followed by 31P NMR, checking the disappearance of the precursor’s signals. When the maximum conversion of the precursor was obtained, the solution was concentrated under a vacuum up to a quarter of the original volume, cooled (0 °C) and treated with n-heptane (20–30 mL). A waxy solid precipitated, which turned into a colorless powder upon prolonged stirring (3–12 h). The product was filtered, washed with n-heptane (2 × 3 mL) and dried under a vacuum. For each NAC derivative, the isocyanide complex used, the yield, the elemental analysis and the spectroscopic (IR and NMR) characterizations are reported.
Cis-[PtBr2(PPh3)C(NHCH2Ph)(NEt2)] (5). [PtBr2(PPh3)(CNCH2Ph)], 0.196 g (69%).
El. Anal. Calcd C30H33Br2N2PPt, % C 44.6, H 4.1 and N 3.5. Found, % C 45.0, H 4.0% and N 3.7%.
IR (ATR, ν, cm−1): 3056 w, 2982 w, 2928 w, 1554 s (stretching C=N), 1434 s, 1379 w, 1095 m, 998 m, 749 m and 691 s.
31P NMR: 9.22 (1JP-Pt = 4010 Hz).
1H NMR: 7.70–7.10 (2 m, 20H, Harom), 5.65 (dd, 1H, J = 13.0 Hz, J’ = 4 Hz, PhCHH), 4.96 (bm, 1H, 3JH-Pt = 80 Hz, NH), 4.79 (m, 1H, CH3CHHN), 4.44 (dd, 1H, J = 13.0 Hz, J’ = 4.0 Hz, PhCHH), 3,64 (m, 1H, CH3CHHN), 2.83 (m, 2H,CH’3CH’2N), 1.19 (t, 3H, J = 6.0 Hz, CH3CH2N) and 0.89 (t, 3H, J = 6.0 Hz, CH’3CH’2N).
13C NMR: 162.7, 134.8, 134.7, 134.6, 131.2, 129.0, 128.5, 128.3, 128.2, 53.7, 53.0, 43.3, 13.0 and 12.2.
195Pt NMR: −4159 (1JP-Pt = 4010 Hz).
[PtBr2(PPh3)C(NHC6H4(OCH3))(NEt2)] (6). [PtBr2(CNC6H4(OCH3))(PPh3)], 0.235 g (87%). Mixture of isomers.
El. Anal. Calcd C30H33Br2N2OPPt, % C 43.8, H 4.0 and N 3.4. Found, % C 43.9, H 3.8% and N 3.3%.
IR (ATR, ν, cm−1): 3059 w, 2932 w, 1611 w, 1545 s (stretching C=N), 1508 s, 1435 s, 1337 m, 1250 s, 1173 w, 1094 m, 1032 m, 833 m and 753 m.
31P NMR: 8.36 (1JP-Pt = 4076 Hz, 80%) and 8.56 (1JP-Pt =4045 Hz, 20%).
1H NMR: Isomer A (selected signals): 7.80–7.00 (m, 17H, Harom), 6.88–6.63 (m, 3H, Harom + NH), 4.76 (m, 1H, NCHHCH3), 4.15 (m, 1H, NCHHCH3), 3.84 (s, 3H, OCH3), 3.20 (m, 2H, NCH’2CH3), 1.23 (t, 3H, NCH2CH3) and 1.07 (t, 3H, NCH’2CH’3).
Isomer B (selected signals): 7.80–7.00 (m, 17H, Harom), 6.88–6.63 (m, 3H, Harom + NH), 4.84 (m, 1H, NCHHCH3), 4.02 (m, 1H, NCHHCH3), 3.84 (s, 3H, OCH3), 2.97 (m, 2H, NCH’2CH3), 1.40 (t, 3H, NCH2CH3) and 0.86 (t, 3H, NCH’2CH’3).
13C NMR (mixture of isomers): 158.2, 157.5, 134.9, 134.7, 134.6 (2C), 134.5 (2C), 132.4, 132.3, 130.9 (2C), 128.1, 128.0 (2C), 127.9, 127.8, 113.5 (2C), 55.6, 53.6, 44.7 (2C), 41.9, 22.7, 22.3, 12.8 and 12.3.
195Pt NMR (only the most abundant isomer was observed): −4130 (1JP-Pt = 4076 Hz).

5. Single-Crystal X-ray Diffraction

Single-crystal X-ray diffraction was performed with a Bruker D8 Venture instrument equipped with microfocus Mo source (Kα radiation, λ = 0.71073 Å) and a 2D Photon III detector. The main experimental details regarding the determination of the structure of 3 by single-crystal X-ray diffraction are reported in Table 3. In detail, a specimen of C53H45Br4Cl3N2O2P2Pt2, approximate dimensions 0.100 mm × 0.200 mm × 0.400 mm, was used for the X-ray crystallographic analysis. The integration of the data using a triclinic unit cell yielded a total of 100,548 reflections to a maximum θ angle of 28.27° (0.75 Å resolution), of which 13,634 were independent (average redundancy 7.375, completeness = 98.4%, Rint = 5.02%, Rsig = 3.59%) and 12,364 (90.69%) were greater than 2σ(F2). The final cell constants of a = 10.6145(3) Å, b = 14.8776(4) Å, c = 18.7841(4) Å, α = 103.8190(10)°, β = 103.3390(10)°, γ = 90.3250(10)° and volume = 2796.98(13) Å3 are based upon the refinement of the XYZ-centroids of reflections above 20 σ(I). The calculated minimum and maximum transmission coefficients (based on crystal size) are 0.1400 and 0.4980. The final anisotropic full-matrix least-squares refinement on F2 with 615 variables converged at R1 = 3.67% for the observed data and wR2 = 11.14% for all data. The goodness-of-fit was 1.099. The largest peak in the final difference electron density synthesis was 1.183 e−/Å3 and the largest hole was −2.282 e−/Å3 with an RMS deviation of 0.199 e−/Å3. On the basis of the final model, the calculated density was 1.924 g/cm3 and F(000), 1540 e−.

Supplementary Materials

The following supporting information can be downloaded at https://0-www-mdpi-com.brum.beds.ac.uk/article/10.3390/inorganics11040137/s1: synthesis of cis-[PtCl2(PPh3)(CNtert-Bu)], cis-[PtCl2(PPh3)(CNCH2COOEt)], [PtBr2(NCMe)2] and trans-[Pt(μ-Br)Br(PPh3)]2; Figures S1–S6: spectroscopic study (1H- and 31P NMR) of the stability of complex 5 in DMSO-d6; and Figures S7–S28: IR, 1H-, 31P-, 13C- and 195Pt NMR spectra of complexes 1–6. CCDC 2244083 for cis-[PtBr2(PPh3)(CNC6H4OMe)] (3) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre.

Author Contributions

Conceptualization, S.S. and L.L.; methodology, A.F.; data analysis and evaluation of data, M.T., A.F., F.N., L.L. and S.S.; writing—original draft preparation, L.L. and S.S.; writing—review and editing, L.L. and S.S.; supervision, L.L. and S.S.; and funding acquisition, L.L. and S.S. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by Pisa University, Fondi di Ateneo 2020 and Progetti di Ricerca di Ateneo 2020—PRA_2020_39.

Data Availability Statement

The data presented in this study are available in Supplementary Materials.

Acknowledgments

The University of Pisa (Fondi di Ateneo 2020 and Progetti di Ricerca di Ateneo 2020—PRA_2020_39) and Interuniversity Consortium for the Research on the Chemistry of Metals in Biological Systems (CIRCMSB) are gratefully acknowledged. The Center for the Integration of Scientific Instruments of the University of Pisa (CISUP) is acknowledged for providing access to the Bruker D8 Venture diffractometer. Thanks are due to Chiara Palestini for preliminary experiments. Massimo Guelfi is acknowledged for support during the X-ray diffraction data collection and analysis.

Conflicts of Interest

The authors declare no conflict of interest.

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Inorganics 11 00137 sch001 550
Scheme 1. Synthesis of isonitrile complexes 1–4.
Scheme 1. Synthesis of isonitrile complexes 1–4.
Inorganics 11 00137 sch001
Inorganics 11 00137 g001 550
Figure 1. Structure of complex 3. Dark gray: carbon; Light gray: hydrogen; Green: chlorine; Brown: Bromine; Yellow: phosphorus; White: platinum; Blue: nitrogen; Red: oxygen.
Figure 1. Structure of complex 3. Dark gray: carbon; Light gray: hydrogen; Green: chlorine; Brown: Bromine; Yellow: phosphorus; White: platinum; Blue: nitrogen; Red: oxygen.
Inorganics 11 00137 g001
Inorganics 11 00137 sch002 550
Scheme 2. Synthesis of NAC derivatives 5 and 6.
Scheme 2. Synthesis of NAC derivatives 5 and 6.
Inorganics 11 00137 sch002
Inorganics 11 00137 g002 550
Figure 2. 1H NMR spectrum (CDCl3) of complex 5.
Figure 2. 1H NMR spectrum (CDCl3) of complex 5.
Inorganics 11 00137 g002
Table
Table 1. Isolated yields and isomeric compositions (CDCl3, equilibrium) of [PtBr2(PPh3)(CNR)].
Table 1. Isolated yields and isomeric compositions (CDCl3, equilibrium) of [PtBr2(PPh3)(CNR)].
ComplexR% Yieldcis,trans % a
1Bz9359/41
2Tert-Bu9885/15
34-(MeO)C6H47576/24
4CH2COOEt83100/0
a Calculated by integration of 31P NMR signals in solution.
Table
Table 2. Most significant bond lengths and angles for complex 3.
Table 2. Most significant bond lengths and angles for complex 3.
Bond lengths (Å)
Pt1-C11.910 (5)Pt1-P12.2563 (12)
Pt1-Br22.4317 (6)Pt1-Br12.4886 (6)
Pt2-C271.897 (5)Pt2-P22.2536 (10)
Pt2-Br32.4358 (5)Pt2-Br42.4754 (5)
Bond angles (°)
P1-Pt1-Br289.77 (3)P1-Pt1-Br1179.32 (3)
C1-Pt1-P192.48 (16)C1-Pt1-Br2177.19 (17)
C1-Pt1-Br186.88 (16)C1-N1-C2179.4 (6)
C27-Pt2-Br488.43 (13)C27-Pt2-Br3177.91 (14)
C27-Pt2-P291.74 (13)C27-N2-C28172.5 (5)
P2-Pt2-Br4179.69 (3)P2-Pt2-Br388.86 (3)
Br3-Pt2-Br490.986 (19)Br2-Pt1-Br190.86 (3)
Table
Table 3. Crystal data for cis-[PtBr2(PPh3)(CNC6H4OMe)] (3).
Table 3. Crystal data for cis-[PtBr2(PPh3)(CNC6H4OMe)] (3).
Identification codeCP9
Empirical formulaC53H45Br4Cl3N2O2P2Pt2
Formula weight1620.02 g/mol
Temperature293(2) K
Wavelength0.71073 Å
Crystal systemTriclinic
Space groupP-1
Unit cell dimensionsa = 10.6145(3)Åα = 103.8190(10)°
b = 14.8776(4) Åβ = 103.3390(10)°
c = 18.7841(4)Åγ = 90.3250(10)°
Volume2796.98(13) Å3
Z2
Density (calculated)1.924 g/cm3
Absorption coefficient8.93 mm−1
F(000)1540
Theta range for data collection1.98 to 28.27°
Index ranges−14 ≤ h ≤ 14, −19 ≤ k ≤ 19, −25 ≤ l ≤ 24
Reflections collected100,548
Independent reflections13,634 [R(int) = 0.0502]
Max. and min. transmission0.4980 and 0.1400
Refinement methodFull-matrix least-squares on F2
Data/restraints/parameters13,634/0/615
Goodness-of-fit on F21.099
Final R indices 12,364 data; I > 2σ(I)R1 = 0.0367, wR2 = 0.1041
all dataR1 = 0.0406, wR2 = 0.1114
Weighting schemew = 1/[σ2(Fo2) + (0.0675P)2 + 3.3100P]
Largest diff. peak and hole1.183 and −2.282 eÅ−3
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Farasat, A.; Nerli, F.; Labella, L.; Taddei, M.; Samaritani, S. Dibromo–Isonitrile and N-acyclic Carbene Complexes of Platinum(II): Synthesis and Reactivity. Inorganics 2023, 11, 137. https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics11040137

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Farasat A, Nerli F, Labella L, Taddei M, Samaritani S. Dibromo–Isonitrile and N-acyclic Carbene Complexes of Platinum(II): Synthesis and Reactivity. Inorganics. 2023; 11(4):137. https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics11040137

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Farasat, Anna, Francesca Nerli, Luca Labella, Marco Taddei, and Simona Samaritani. 2023. "Dibromo–Isonitrile and N-acyclic Carbene Complexes of Platinum(II): Synthesis and Reactivity" Inorganics 11, no. 4: 137. https://0-doi-org.brum.beds.ac.uk/10.3390/inorganics11040137

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