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Communication

AuIII Acyclic (Amino)(N-Pyridinium)carbenoids: Synthesis via Addition of 2-PySeCl to AuI-Bound Isonitriles, Structures, and Cytotoxicity

by
Olga V. Repina
1,
Alexey S. Kubasov
2,
Anna V. Vologzhanina
3,
Alexander V. Borisov
4,
Ilya S. Kritchenkov
1,
Ksenia M. Voroshilkina
5,
Alexey A. Nazarov
5,
Dmitriy M. Shchevnikov
1,
Mariya V. Grudova
1,
Rosa M. Gomila
6,
Antonio Frontera
6,
Valentine G. Nenajdenko
5,*,
Andreii S. Kritchenkov
1,7 and
Alexander G. Tskhovrebov
1,*
1
Research Institute of Chemistry, Peoples’ Friendship University of Russia, 6 Miklukho-Maklaya Street, 117198 Moscow, Russia
2
Kurnakov Institute of General and Inorganic Chemistry, 31 Leninsky Prosp., 119991 Moscow, Russia
3
Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova St. 28, 119334 Moscow, Russia
4
Institute of Chemistry, R.E. Alekseev Nizhny Novgorod State Technical University, Minin St. 24, 603155 Nizhny Novgorod, Russia
5
Department of Chemistry, M.V. Lomonosov Moscow State University, 1 Leninskie Gory, 119991 Moscow, Russia
6
Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain
7
Branch of Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre «Kurchatov Institute»—Institute of Macromolecular Compounds, Bolshoi pr. VO 31, 199004 St. Petersburg, Russia
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(2), 483; https://doi.org/10.3390/ijms26020483
Submission received: 5 December 2024 / Revised: 31 December 2024 / Accepted: 6 January 2025 / Published: 8 January 2025
(This article belongs to the Special Issue Noncovalent Interactions and Applications in Materials and Catalysis)
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Abstract

:
In this study, we report the first example of acyclic (amino)(N-pyridinium)carbenoid gold(III) complexes synthesized via a coupling reaction between 2-pyridylselenyl chloride and Au(I)-bound isonitriles. The reaction involves an initial oxidative addition of the Se–Cl moiety to Au(I), followed by the nucleophilic addition of the pyridine fragment to the isonitrile’s C≡N bond, furnishing a metallacycle. Importantly, this is the first example of the pyridine acting as a nucleophile towards metal-bound isonitriles. Arguably, such an addition is due to the chelate effect. The structures of the gold(III) carbenoid complexes were unambiguously established using X-ray diffraction and NMR spectroscopy. Theoretical calculations, including DFT, Natural Resonance Theory (NRT), and Meyer bond order (MBO) analyses, were used to analyze the different resonance forms. The reaction mechanism was further elucidated using DFT calculations, which identified the oxidative addition as the rate-determining step with a barrier of 29.7 kcal/mol. The nucleophilic addition proceeds with a minimal barrier, making the reaction highly favorable. The antiproliferative activity of new compounds 2a–2e was tested against two human cancer cell lines: A2780 ovarian adenocarcinoma and the A278Cis cisplatin-resistant variant.

1. Introduction

Nitrogen-stabilized carbene complexes are of paramount importance in organometallic chemistry, with applications in catalysis, the development of novel antitumor agents, etc. [1,2,3]. N-heterocyclic carbenes (NHCs) currently represent one of the most applicable classes of ancillary ligands in catalysis [4,5]. These carbenes are stable in the free state and were first isolated by Arduengo in 1991 (Scheme 1) [6].
These ligands are particularly significant due to their prominent role in organometallic chemistry and catalysis, where they have emerged as strong competitors to the widely employed phosphine ligands. Many of their complexes serve as catalysts of choice in various organic transformations. Additionally, their electronic and geometric properties can be modified more easily than those of phosphines, offering greater versatility and tunability in catalytic applications.
The most popular NHCs are typically derived from imidazolium salts and, to a lesser extent, imidazolidinium salts. These carbenes are generated through the action of strong bases on the respective salts. Numerous methods have been developed for synthesizing various precursors of NHCs [7]. The significance of this class of ligands has driven extensive research on diverse approaches to the synthesis of their precursors. While these methods are not detailed in this work, they are comprehensively summarized in several review papers [7,8,9,10,11,12,13].
In contrast, acyclic diaminocarbenes (ADCs) have received less attention. Importantly, ADCs have demonstrated their ability to act as strong σ-donor ligands. In 2002, Herrmann showed that ADC ligands induce greater electron density at Rh(I) compared to both saturated and unsaturated five-membered NHCs, as evidenced by the ν(CO) values of the square planar Rh(I) carbonyl complexes [14].
However, ADC complexes have one significant advantage over NHC complexes, which is their synthesis via nucleophilic addition to metal-activated isonitriles [15,16,17,18,19,20,21,22,23,24,25]. This route unlocks structures with easily variable steric and electronic properties.
Gold(I) and (III) have shown remarkable efficacy in promoting nucleophilic addition to isonitriles producing ADC complexes [26,27,28,29,30]. The latter has shown promise in catalysis and antiproliferative activity, which is widely being explored currently [31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46].
Here, we describe the addition of 2-pyridylselenyl chloride to gold(I)-bound isonitriles producing acyclic (amino)(N-pyridinium)carbenoid gold(III) complexes. This is the first example of pyridine acting as a nucleophile in metal-mediated addition to isonitriles. Moreover, novel structures were tested against two human cancer cell lines.

2. Results and Discussion

For this study, we used Au(I) isocyanide complexes, which were obtained in situ by reacting the corresponding isocyanides with [(Me2S)AuCl] in dichloromethane. The addition of 2-pyridylselenyl chloride to solutions of Au(I) isocyanide complexes in CH2Cl2 resulted in a gradual formation of orange precipitates (Scheme 2). The isolation and analysis of the solids suggested the formation of the adducts of 2-pyridylselenyl chloride with isocyanide-gold(I) chloride in 32–57% yields (Scheme 2).
Complexes 2a–2e are stable at room temperature and exhibit very poor solubility in most organic solvents. However, they are moderately soluble in highly polar solvents such as DMF or DMSO, which allows their characterization by the NMR technique. The 13C NMR spectra of 2a–2e (see Section 3) exhibited new characteristic peaks in the range of 163–153 ppm, indicating carbenoid species formation.
Interestingly, aliphatic isocyanide gold(I) complexes did not produce carbenoid species like 2a–2e upon reaction with 2-PySeCl. The addition of 2-PySeCl to tert-butyl isocyanide gold(I) chloride resulted in the formation of isocyanide Au(III) trichloride and 2,2′-dipyridyl diselenide as products (Scheme 3). In this case, 2-PySeCl acted as a chlorinating agent.
The carbenoid complexes 2a and 2c–2e could be recrystallized from dichloromethane to produce crystals suitable for X-ray single-crystal analysis, which confirmed the formation of Au(III) carbenoid complexes (Figure 1, Tables S1–S13 and Figures S1–S4).
Single crystals of 2e contain dichloromethane molecules, while the other complexes crystallize without a solvent. The asymmetric unit of 2c contains two independent molecules. For all complexes, Au(III) achieves a distorted square geometry with a twisted disposition of two chlorine and C, Se atoms (Figure 1, Table 1). The Au–C distance is the shortest, and the Au–Se distance is the longest.
The structures of 2a–2e could be described by the mesomeric forms A–D (Scheme 4).
The bond distances in the ligand demonstrate that the main mesomeric form for 2-pyridine-selenyl carbene complexes is mesomeric form A with single C–Se and double N=C(carbenoid) bonds. The length of the C–NPh bond is affected by electronic effects from substituents at different positions in the phenyl ring. The ligand chelates the gold(III) atom with the formation of a rigid five-membered cycle; however, the angle between the pyridine ring and the mean plane formed by the AuCl2 fragment varies from 20.1(2) to 36.50(13). The angle between an aryl ring and the pyridine cycle is equal to 15.3(3)–60.4(10) due to rotation around a single N–C bond.
To gain a deeper insight into which mesomeric forms (Scheme 4) contribute most to the final structure, we performed additional theoretical calculations. Specifically, the percentage of each form was computed using Natural Resonance Theory (NRT) within the Natural Bond Orbital (NBO) framework, along with Meyer bond order (MBO) values. The NRT results indicate negligible contributions from forms C and D, while form A dominates, with a 70% contribution. This aligns well with the MBO analysis (see Figure 2), which shows that the Npy–C(Au) bond has a bond index below 1, effectively ruling out any significant contribution from resonance form C, which involves a Npy=C(Au) double bond. The MBO values for all coordination bonds are approximately 0.7, typical of coordination bonds with bond orders less than 1, further excluding any double bond character between the gold and carbon atoms, thereby dismissing resonance form D. Additionally, the MBO value of nearly 2 for the Nph–C(Au) bond is consistent with forms A and B, confirming no contribution from forms C or D. Finally, the MBO value of 1.2 for both the C–Se and pyridine C–N bonds suggests some contribution from resonance form B, corroborated by NRT calculations.
Although the nucleophilic addition to the C≡N triple bond of metal-bound isonitriles is well documented and widely studied in the context of the synthesis of metal carbene complexes and their applications, this is the first example of pyridine functioning as a nucleophile in a metal-mediated coupling with isonitriles. As a result, this represents the first example of acyclic (amino)(N-pyridinium)carbenoid metal complexes.
The mechanism of the new coupling reaction between 2-pyridylselenyl chloride and Au(I) isocyanide complexes formally involves two key steps: the oxidative addition of the Se–Cl moiety to Au(I) and the nucleophilic addition of the pyridine fragment to the isonitrile’s CN triple bond. These steps may occur either sequentially or simultaneously. To elucidate the mechanism, we performed additional DFT calculations, which ruled out the simultaneous mechanism. For computational efficiency, we simplified the isocyanide complex to CH3-N≡C–Au–Cl. We explored the potential energy surface connecting the [(Me2S)AuCl] and CH3-N≡C–Au–Cl reactants to the final adduct using the NEB-TS (Nudged Elastic Band with TS optimization) method, which locates the transition state (TS) by using the geometries of the reactants and products. The NEB-TS analysis identified an intermediate corresponding to the oxidative addition of the Se–Cl moiety to Au(I) (Figure 3). Starting from this intermediate, we computed two transition states, linking it to both the reactants and the product. The ΔG values in CH2Cl2 reveal that the oxidative addition is the rate-determining step, with a barrier of 29.7 kcal/mol. Interestingly, the reactants form a supramolecular complex prior to the oxidative addition, where the Se atom is preorganized 3.028 Å from the Au atom. The second step, the nucleophilic addition of the pyridine fragment to the CN bond, occurs with a minimal barrier of 0.3 kcal/mol, leading to the final product, which is 12.5 kcal/mol more stable than the starting material.
Gold carbene complexes are known for their anticancer activity. The antiproliferative activity of new compounds 2a–2e was tested against two human cancer cell lines, A2780 ovarian adenocarcinoma and the A278Cis cisplatin-resistant variant, using the standard MTT colorimetric assay. Cisplatin was used as a control in the study. The new compounds 2a–2e demonstrated high antiproliferative activity in the low micromolar range. They were about 3–5 times more potent than cisplatin against the cisplatin-sensitive cell line and about 5–6 times more potent against the cisplatin-resistant variant (Table 2).
Among the new compounds, the one with the nitro group 2d was found to be the most active against both cancer cell lines. When comparing the antiproliferative activity of the new compounds against the A2780 and A2780 cis cell lines, it was found that the complexes were less potent against cisplatin-resistant cells (Table 2, Rf); however, the resistant index was lower compared to the cisplatin. These results suggest that the new compounds may have a different mode of action compared to cisplatin, which will be studied in more details in the future.

3. Methods

3.1. Experimental Details

General remarks. No uncommon hazards were noted as stemming from the experimental work carried out. All manipulations were carried out in air. All the reagents used in this study were obtained from commercial sources (Aldrich, TCI-Europe, Strem, ABCR). Commercially available solvents were purified by conventional methods and distilled immediately prior to use. Mass spectra were recorded on a Bruker micrOTOF spectrometer equipped with an electrospray ionization (ESI) source; MeOH or MeCN was used as a solvent. NMR spectra were recorded on a Bruker Avance neo 700; chemical shifts (δ) are given in ppm, and coupling constants (J) are given in Hz. IR spectra were recorded on a Shimadzu Inspirit IR–Fourier spectrometer equipped with the QATAR-Singapore attenuated total reflectance sample holder.
Synthetic part.
Ijms 26 00483 i001
Compound 2a. 1 [(Me2S)AuCl] (15 mg, 0.05 mmol) was added to a solution of p-bromophenyl isocyanide (9 mg, 0.05 mmol) in CH2Cl2 (2 mL), and the solution was stirred for 15 min. After that, a solution of 2-PySeCl (10 mg, 0.05 mmol) in CH2Cl2 (3 mL) was added to the mixture, which was stirred for 4 h. An orange precipitate formed, which was filtered off and washed with MeOH (3 mL) and Et2O (3 mL) and dried under a vacuum. Yield: 15 mg, 48%. 1H NMR (400 MHz, DMSO-d6) δ 9.33 (d, J = 6.6 Hz, 1H), 8.34 (d, J = 8.2 Hz, 1H), 8.26 (t, J = 7.7 Hz, 1H), 7.74 (t, J = 6.9 Hz, 1H), 7.62 (d, J = 8.5 Hz, 2H), 7.14 (d, J = 8.5 Hz, 2H). 13C NMR (101 MHz, DMSO) δ 154.4, 146.5, 146.1, 144.4, 142.3, 131.7, 127.6, 123.3, 122.9, 119.0. MS (ESI+): found, 606.8143 [M]+; calcd for C12H8AuBrCl2N2Se, 606.8151. Crystals, suitable for X-ray analysis, were obtained directly from the reaction mixture.
Ijms 26 00483 i002
Compound 2b [(Me2S)AuCl] (15 mg, 0.05 mmol) was added to a solution of p-iodophenyl isocyanide (12 mg, 0.05 mmol) in CH2Cl2 (2 mL), and the solution was stirred for 15 min. A white precipitate formed. After that, a solution of 2-PySeCl (10 mg, 0.05 mmol) in CH2Cl2 (3 mL) was added to the mixture, which caused the white precipitate to dissolve, and the mixture was stirred for 4 h. An orange precipitate formed, which was filtered off and washed with MeOH (3 mL) and Et2O (3 mL) and dried under a vacuum. Yield: 20 mg, 51%. 1H NMR (400 MHz, DMSO-d6) δ 9.32 (d, J = 6.3 Hz, 1H), 8.34 (d, J = 8.2 Hz, 1H), 8.25 (t, J = 7.7 Hz, 1H), 7.81–7.68 (m, 3H), 7.00 (d, J = 8.5 Hz, 2H). 13C NMR (101 MHz, DMSO-d6) δ 154.3, 146.5, 145.9, 144.7, 142.3, 138.6, 137.5, 127.6, 123.4, 122.9. MS (ESI+): found, 654.8017 [M]+; calcd for C12H8AuICl2N2Se, 654.8013.
Ijms 26 00483 i003
Compound 2c [(Me2S)AuCl] (15 mg, 0.05 mmol) was added to a solution of 2,6-dichlorophenyl isocyanide (9 mg, 0.05 mmol) in CH2Cl2 (2 mL), and the solution was stirred for 15 min. After that, a solution of 2-PySeCl (10 mg, 0.05 mmol) in CH2Cl2 (3 mL) was added to the mixture, which was stirred for 4 h. The reaction mixture was left overnight, and the residue was washed with MeOH (3 mL) and Et2O (3 mL) and dried under a vacuum. Yield: 17 mg, 57%. 1H NMR (700 MHz, DMSO-d6) δ 9.10 (d, J = 6.7, 1H), 8.41 (d, J = 8.0 Hz, 1H), 8.33–8.29 (m, 1H), 7.79 (td, J = 7.1, 1.2 Hz, 1H), 7.53 (d, J = 8.2 Hz, 2H), 7.25 (t, J = 8.1 Hz, 1H). 13C NMR (176 MHz, DMSO-d6) δ 155.79, 153.30, 147.16, 141.32, 140.17, 128.44, 128.01, 126.94, 124.61, 123.40. MS (ESI+): found, 560.8614 [M-Cl]+; calcd for C12H7AuCl3N2Se, 560.8506. Crystals, suitable for X-ray analysis, were obtained from the reaction mixture.
Ijms 26 00483 i004
Compound 2d [(Me2S)AuCl] (15 mg, 0.05 mmol) was added to a solution of p-nitrophenyl isocyanide (8 mg, 0.05 mmol) in CH2Cl2 (2 mL) and then stirred for 15 min. A white precipitate formed. After that, a solution of 2-PySeCl (10 mg, 0.05 mmol) in CH2Cl2 (3 mL) was added to the mixture, which caused the white precipitate to dissolve, and the mixture was stirred for 4 h. The reaction mixture was left overnight, and the residue was washed with MeOH (3 mL) and Et2O (3 mL) and dried under a vacuum. Yield: 12 mg, 41%. 1H NMR (400 MHz, DMSO-d6) δ 9.36 (d, J = 6.5 Hz, 1H), 8.38 (d, J = 8.2 Hz, 1H), 8.33–8.23 (m, 3H), 7.76 (t, J = 6.9 Hz, 1H), 7.39 (d, J = 8.9 Hz, 2H). 13C NMR (101 MHz, DMSO-d6) δ 155.0, 150.6, 148.0, 146.8, 144.9, 142.5, 127.60, 124.6, 122.9, 121.8. MS (ESI+): found, 573.8892 [M]+; calcd for C12H9AuCl2N3O2Se, 573.8897. Crystals, suitable for X-ray analysis, were obtained from the reaction mixture.
Ijms 26 00483 i005
Compound 2e [(Me2S)AuCl] (15 mg, 0.05 mmol) was added to a solution of 2-cyanophenyl isocyanide (7 mg, 0.05 mmol) in CH2Cl2 (2 mL) and then stirred for 15 min. After that, a solution of 2-PySeCl (10 mg, 0.05 mmol) in CH2Cl2 (3 mL) was added to the mixture, which was stirred for 4 h. The reaction mixture was left overnight, and the residue was washed with MeOH (3 mL) and Et2O (3 mL) and dried under a vacuum. Yield: 9 mg, 32%. 1H NMR (400 MHz, DMSO-d6) δ 9.11 (d, J = 6.4 Hz, 1H), 8.39 (d, J = 8.2 Hz, 1H), 8.34–8.24 (m, 1H), 7.87 (d, J = 8.8 Hz, 1H), 7.82 (t, J = 6.9 Hz, 1H), 7.75 (t, J = 8.5 Hz, 1H), 7.43 (t, J = 7.7 Hz, 1H), 7.36 (d, J = 7.9 Hz, 1H).13C NMR (101 MHz, DMSO-d6) δ 155.6, 150.5, 147.7, 146.9, 141.5, 134.0, 132.7, 127.8, 126.6, 123.3, 121.5, 117.1, 103.9. MS (ESI+): found, 553.8992 [M]+; calcd for C13H8AuCl2N3Se, 553.8999. Crystals, suitable for X-ray analysis, were obtained from the reaction mixture.

Reaction of [(tBuNC)AuCl] with 2-PySeCl

[(Me2S)AuCl] (15 mg, 0.05 mmol) was added to a solution of tert-butyl isocyanide (4 mg, 0.05 mmol) in CH2Cl2 (2 mL) and the solution was stirred for 15 min. After that, a solution of 2-PySeCl (20 mg, 0.1 mmol) in CH2Cl2 (3 mL) was added to the mixture and stirred overnight. Then, the reaction mixture was concentrated under a vacuum and separated by column chromatography (eluent: DCM) to give white crystals of [(tBuNC)AuCl3] and yellow crystals of Py2Se2. Yield: 15 mg (74%) and 15 mg (94%), respectively.

3.2. Theoretical Methods

The structures and relative energies of all systems considered in the mechanistic analysis were optimized at the PBE0-D4/def2-TZVP level of theory using ORCA 5.1 [47]. The hybrid functional PBE0 [48], corrected for dispersion effects with the D4 method [49], was employed alongside a triple-ζ quality basis set [50]. Frequency calculations confirmed the stationary points, ensuring they correspond to minima or transition states. To locate the transition states, the Nudged Elastic Band (NEB) method available in ORCA was applied. This approach identifies a minimum energy pathway by constructing a series of atomic configurations, known as “images” that link the reactant and product states. A detailed explanation of the NEB implementation can be found in the study by Ásgeirsson et al. [51].

4. Conclusions

The reaction between the isonitrile gold(I) complex and 2-pyridylselenyl chloride resulted in the formation of unprecedented (amino)(N-pyridinium)carbenoid gold(III) derivatives. The addition proceeds via two key steps: the oxidative addition of Se–Cl moiety to the Au(I) and the nucleophilic addition of the pyridine group to the CN triple bond of metal-bound isonitrile. Importantly, this is a first example of pyridine acting as a nucleophile in the reaction with the CN bond of isonitrile. Arguably, such an addition is due to the chelate effect. The reaction mechanism was elucidated using DFT calculations, which identified the oxidative addition as the rate-determining step with a barrier of 29.7 kcal/mol.
Moreover, we tested the new compounds 2a–2e against two human cancer cell lines, A2780 ovarian adenocarcinoma and the A278Cis cisplatin-resistant variant, and the new compounds were about 3–5 times more potent than cisplatin against the cisplatin-sensitive cell line and about 5–6 times more potent against the cisplatin-resistant variant.

Supplementary Materials

The following supporting information can be downloaded at: www.mdpi.com/article/10.3390/ijms26020483/s1.

Author Contributions

Conceptualization, A.G.T.; investigation, K.M.V., D.M.S., R.M.G., A.F., A.S.K. (Andreii S. Kritchenkov), O.V.R., A.V.V., A.V.B., M.V.G., A.S.K. (Alexey S. Kubasov) and I.S.K.; methodology, A.A.N.; visualization, V.G.N. All authors have read and agreed to the published version of the manuscript.

Funding

This work was performed with the support of the Russian Science Foundation (award No. 22-73-10007).

Data Availability Statement

Data are contained within the article and Supplementary Materials.

Acknowledgments

The single crystal X-ray diffraction data for 2a, 2c, and 2e were obtained using the equipment of the Shared Facility Center at the Kurnakov Institute, operating with financial support from the Ministry of Science and Higher Education of the Russian Federation. The XRD for 2d was supported by the Ministry of Science and Higher Education of the Russian Federation (Contract No. 075-00277-24-00, project № 021341-2-000). Theoretical investigations were funded by the “Ministerio de Ciencia, Investigacion y Universidades/Agencia Estatal de Investigación” (MICIU/AEI/10.13039/501100011033) of Spain (project PID2020-115637GB-I00. FEDER funds). The authors acknowledge support from the M.V. Lomonosov Moscow State University Program of Development (the “Feyond-A400” microplate reader (Allsheng, China) for the MTT assay).

Conflicts of Interest

The authors declare no conflicts of interest.

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Ijms 26 00483 sch001
Scheme 1. Synthesis of isolable NHC by Arduengo.
Scheme 1. Synthesis of isolable NHC by Arduengo.
Ijms 26 00483 sch001
Ijms 26 00483 sch002
Scheme 2. Synthesis of 2a–2e.
Scheme 2. Synthesis of 2a–2e.
Ijms 26 00483 sch002
Ijms 26 00483 sch003
Scheme 3. Oxidation of tert-butyl isocyanide gold(I) chloride to gold(III) trichloride by 2-PySeCl.
Scheme 3. Oxidation of tert-butyl isocyanide gold(I) chloride to gold(III) trichloride by 2-PySeCl.
Ijms 26 00483 sch003
Ijms 26 00483 g001
Figure 1. Ball-and-stick representations of crystal structures of 2a and 2c–2e. Gray and light-gray spheres represent carbon and hydrogen, respectively.
Figure 1. Ball-and-stick representations of crystal structures of 2a and 2c–2e. Gray and light-gray spheres represent carbon and hydrogen, respectively.
Ijms 26 00483 g001
Ijms 26 00483 sch004
Scheme 4. Mesomeric forms for AuIII carbenoid complexes 2a–2e.
Scheme 4. Mesomeric forms for AuIII carbenoid complexes 2a–2e.
Ijms 26 00483 sch004
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Figure 2. RI-BP86-D4/def2-TZVP optimized geometry of compound 2d, indicating the Meyer bond order.
Figure 2. RI-BP86-D4/def2-TZVP optimized geometry of compound 2d, indicating the Meyer bond order.
Ijms 26 00483 g002
Ijms 26 00483 g003
Figure 3. Energetic profile for the reaction of [(Me2S)AuCl] with CH3-N≡C–Au–Cl at the RI-BP86-D4(CH2Cl2)/def2-TZVP level of theory. Distances are shown in Å.
Figure 3. Energetic profile for the reaction of [(Me2S)AuCl] with CH3-N≡C–Au–Cl at the RI-BP86-D4(CH2Cl2)/def2-TZVP level of theory. Distances are shown in Å.
Ijms 26 00483 g003
Table 1. Selected interatomic distances and angles (Å, °) in 2a and 2c–2e.
Table 1. Selected interatomic distances and angles (Å, °) in 2a and 2c–2e.
Parameter2a2c2d2e
Au−Cl2.244(2)–2.357(2)2.330(3)–2.354(3)2.3371(14)–2.3427(13)2.333(2)–2.349(2)
Au−Se2.4060(9)2.3699(15)–2.3866(15)2.3910(6)2.3878(16)
Au−C2.021(9)1.983(13)–2.024(13)2.020(5)2.022(6)
C–Se1.884(9)1.869(13)–1.873(14)1.881(5)1.877(6)
N=C1.239(12)1.267(18)–1.285(18)1.247(7)1.257(7)
C–NPy1.481(10)1.473(14)–1.493(15)1.472(7)1.473(7)
C–NPh1.427(11)1.368(16)–1.372(16)1.421(7)1.403(7)
Cl–Au–Cl89.93(7)91.5(1)–93.6(1)91.84(5)91.78(9)
C–Au–Se83.2(2)83.6(4)–86.1(4)84.47(15)84.31(17)
α1 a15.3(3)24.3(5)–26.3(5)52.3(8)60.4(10)
α2 b36.50(13)20.1(2)–27.1(2)30.78(9)35.42(11)
a The fold angle between the pyridine and phenyl cycles. b The fold angle between the 2-pyridylselenyl and the AuCl2 fragments.
Table 2. Antiproliferative activity of 2-pyridine-selenyl gold (III) carbene complexes 2a–e and cisplatin against human cancer cells. Rf (resistance factors) showed the resistance coefficient. The results are the mean values ± SD of three independent experiments, each of which was performed in triplicate.
Table 2. Antiproliferative activity of 2-pyridine-selenyl gold (III) carbene complexes 2a–e and cisplatin against human cancer cells. Rf (resistance factors) showed the resistance coefficient. The results are the mean values ± SD of three independent experiments, each of which was performed in triplicate.
CompoundsIC50 (72 h)/μM
A2780A2780CisRf
2a0.70 ± 0.072.87 ± 0.084.1
2b0.97 ± 0.132.59 ± 0.032.7
2c1.09 ± 0.042.91 ± 0.192.7
2d0.52 ± 0.072.47 ± 0.114.7
2e0.71 ± 0.062.65 ± 0.173.7
Cisplatin2.64 ± 0.3515.6 ± 2.15.9
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Repina, O.V.; Kubasov, A.S.; Vologzhanina, A.V.; Borisov, A.V.; Kritchenkov, I.S.; Voroshilkina, K.M.; Nazarov, A.A.; Shchevnikov, D.M.; Grudova, M.V.; Gomila, R.M.; et al. AuIII Acyclic (Amino)(N-Pyridinium)carbenoids: Synthesis via Addition of 2-PySeCl to AuI-Bound Isonitriles, Structures, and Cytotoxicity. Int. J. Mol. Sci. 2025, 26, 483. https://doi.org/10.3390/ijms26020483

AMA Style

Repina OV, Kubasov AS, Vologzhanina AV, Borisov AV, Kritchenkov IS, Voroshilkina KM, Nazarov AA, Shchevnikov DM, Grudova MV, Gomila RM, et al. AuIII Acyclic (Amino)(N-Pyridinium)carbenoids: Synthesis via Addition of 2-PySeCl to AuI-Bound Isonitriles, Structures, and Cytotoxicity. International Journal of Molecular Sciences. 2025; 26(2):483. https://doi.org/10.3390/ijms26020483

Chicago/Turabian Style

Repina, Olga V., Alexey S. Kubasov, Anna V. Vologzhanina, Alexander V. Borisov, Ilya S. Kritchenkov, Ksenia M. Voroshilkina, Alexey A. Nazarov, Dmitriy M. Shchevnikov, Mariya V. Grudova, Rosa M. Gomila, and et al. 2025. "AuIII Acyclic (Amino)(N-Pyridinium)carbenoids: Synthesis via Addition of 2-PySeCl to AuI-Bound Isonitriles, Structures, and Cytotoxicity" International Journal of Molecular Sciences 26, no. 2: 483. https://doi.org/10.3390/ijms26020483

APA Style

Repina, O. V., Kubasov, A. S., Vologzhanina, A. V., Borisov, A. V., Kritchenkov, I. S., Voroshilkina, K. M., Nazarov, A. A., Shchevnikov, D. M., Grudova, M. V., Gomila, R. M., Frontera, A., Nenajdenko, V. G., Kritchenkov, A. S., & Tskhovrebov, A. G. (2025). AuIII Acyclic (Amino)(N-Pyridinium)carbenoids: Synthesis via Addition of 2-PySeCl to AuI-Bound Isonitriles, Structures, and Cytotoxicity. International Journal of Molecular Sciences, 26(2), 483. https://doi.org/10.3390/ijms26020483

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