Haresh Sivarama, Jackie Tanb and Han Vinh Huynh*a
aDepartment of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Republic of Singapore. E-mail: chmhhv@nus.edu.sg; Fax: +65 6779 1691; Tel: +65 6516 2670
bDepartment of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Republic of Singapore
First published on 17th June 2013
A series of cationic gold(I) heteroleptic complexes bearing the pyrazole-derived N-heterocyclic carbene (NHC) FPyr (1,2,3,4,6,7,8,9-octahydropyridazino[1,2-a]indazolin-11-ylidene), and either a 1,3-disubstituted benzimidazole-derived NHC of the type RR′-bimy (3: R = R′ = CHPh2; 4: R = CHPh2, R′ = iPr; 5: R = R′ = CH2Ph; 6: R = R′ = iBu; 7: R = R′ = n-Pr; 8: R = R′ = Et; 9: R = R′ = 2-propenyl) or a non-NHC co-ligand L (10: L = PPh3; 11: L = P(OPh)3; 12: L = DMAP) (DMAP = 4-dimethylaminopyridine) have been synthesized from [AuCl(FPyr)] (1). Complexes 3–12 have been characterized using multinuclei NMR spectroscopies, ESI mass spectrometry, and elemental analysis. X-ray diffraction analyses have been performed on complexes 5, 6, and 9–11. To the best of our knowledge, 11 represents the first gold–NHC complex to bear the P(OPh)3 ligand. The cytotoxic activities of complexes 3–12 have been studied in vitro with the NCI-H1666 non-small cell lung cancer cell line.
Therefore, as our maiden contribution to this field of research, we had recently published the cytotoxic activities of a range of gold(I) and gold(III) mono-, homo-bis- and hetero-bis(carbene) complexes bearing benzimidazole- and/or pyrazole-derived NHC ligands on the NCI-H1666 non-small cell lung cancer cell line.6 The preliminary study revealed that the cationic bis(carbene) complexes are far more active as cytotoxic agents when compared with the neutral monocarbene complexes. The gold(I) hetero-bis(carbene) complex 2 (Fig. 1), in particular, shows superior performance with an IC50 value of 0.241 μM. Based on these findings, it was proposed that a heteroleptic system in which a strongly donating ligand is situated trans to a relatively weaker donating ligand was necessary for the labilization of the latter. This would create a vacant coordination site that may be essential for the cytotoxic activity of the complex. For example, donor atoms on target proteins, such as thioredoxin reductase,2,5,7 could bind to the complex fragment when a free coordination site is made available.
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Fig. 1 Gold(I) hetero-bis(carbene) complex [Au(FPyr)(iPr2-bimy)]PF6 (2). |
Spurred by the findings of our initial study, we have extended the investigation to consider a range of other cationic gold(I) heteroleptic complexes bearing the strongly donating pyrazole-derived FPyr (1,2,3,4,6,7,8,9-octahydropyridazino[1,2-a]indazolin-11-ylidene) ligand, and either a 1,3-disubstituted benzimidazole-derived NHC, or a non-NHC co-ligand. Benzimidazolin-2-ylidenes bearing a variety of N-substituents have been considered, in an effort to study the effect on the cytotoxicity of the resultant complexes. For the purpose of comparison with our previous work, the cytotoxic activities of the complexes were studied in vitro with the NCI-H1666 non-small cell lung cancer cell line. We herein report on the syntheses, characterizations, and cytotoxic activities of the aforementioned complexes.
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Scheme 1 Syntheses of cationic gold(I) hetero-bis(carbene) complexes of the type [Au(FPyr)(RR′-bimy)]PF6 (3–9), and heteroleptic complexes of the type [Au(FPyr)(L)]PF6 (10–12). |
Complexes 3–12 were characterized using MS (ESI) and multinuclei NMR spectroscopies. The MS (ESI) spectra of the complexes were particularly useful in confirming the formation of the compounds, given that the base peak observed in all cases corresponds to the [M − PF6]+ fragment. 1H NMR spectroscopy corroborated the successful formation of the complexes, whereby signals from both ligands are observed in the respective spectra. For complexes 3–9, the 13C NMR spectra correspondingly featured two downfield signals as a result of the presence of two carbene carbon atoms in the molecules. These two signals were assigned to their respective carbene carbon atoms by using the previously reported complex 2 as a reference.6 The chemical shift(s) of the carbene carbon atom(s) in complexes 3–12 are presented in Table 1.
Complex | L | FPyr | RR′-bimy |
---|---|---|---|
a All 13C NMR spectra were measured in CDCl3, except for complexes 7, 9 and 12, which were measured in CD3CN due to poor solubility in chloroform.b Doublet, 2J(C,P) = 178 Hz. | |||
3 | (CHPh2)2-bimy | 178.8 | 197.8 |
4 | (iPr2)(CHPh2)-bimy | 179.2 | 195.1 |
5 | (CH2Ph)2-bimy | 179.9 | 195.7 |
6 | iBu2-bimy | 180.2 | 194.8 |
7 | n-Pr2-bimy | 180.0 | 194.8 |
8 | Et2-bimy | 180.7 | 194.1 |
9 | (2-Propenyl)2-bimy | 179.9 | 196.0 |
10 | PPh3 | 182.4 | — |
11 | P(OPh)3 | 179.6b | — |
12 | DMAP | 161.0 | — |
Considering the chemical shift of the FPyr carbene carbon, it is overt that as compared to the gold(I) chlorido monocarbene complex 1 (cf. 167.8 ppm),6 the FPyr carbene carbon in complexes 3–11, resonate at a much more downfield region, ranging from 178.8–182.4 ppm. This is due to the replacement of the chlorido co-ligand in 1 with a stronger donating ligand situated trans to the FPyr ligand in the mentioned complexes, leading to the observed downfield shift of the signal.6,8 On the other hand, complex 12, with its DMAP co-ligand, shows a more upfield FPyr carbene carbon resonance as compared to 1, which is the result of DMAP being a weaker donating ligand as compared to the chlorido ligand.
The changes in the chemical shift of the FPyr carbene carbon also reveal other interesting, albeit unexpected, findings. For example, when focusing on the relevant data for hetero-bis(carbene) complexes 3–9, it is noteworthy that no real correlation can be drawn between the chemical shift of the FPyr carbene carbon and the N-substituents of the RR′-bimy ligands, where the latter would inadvertently influence the overall donating ability of said RR′-bimy ligands. This is unlike the 13C NMR spectroscopic methodology for determining ligand donor strengths that has been reported by our group, wherein even small changes to the N-substituents of various NHCs are shown to affect the donating ability of the ligands, and can be detected by the iPr2-bimy probe in complexes of the type [PdBr2(iPr2-bimy)(NHC)].4a Therefore, the data presented in this work seems to suggest that the Au(I) system is less sensitive than the Pd(II) system when it comes to detecting small changes in donor strength. Furthermore, while the Pd(II) system is able to confirm the stronger donating ability of NHCs as compared to phosphines, the Au(I) system studied in this work suggests the reverse, with the FPyr carbene carbon in [Au(FPyr)(PPh3)]PF6 (10) resonating at 182.4 ppm, which is significantly more downfield as compared to the hetero-bis(carbene) complexes 3–9. This may be due to some unique interactions that the phosphorus donor in PPh3 has with the electron-rich gold(I) metal center, and warrants further investigation.
Single crystals suitable for X-ray diffraction analysis were obtained for complexes 5, 6, and 9–11via vapour diffusion of diethyl ether into solutions of the compounds in either CHCl3 or CH2Cl2. The determined molecular structures were as expected, with all complexes adopting a linear geometry about the gold(I) metal center (Fig. 2). Complex 5 crystallised as the chloroform solvate, while all other complexes crystallised unsolvated. It is interesting to note that unlike 5, where both the benzyl N-substituents are arranged in an anti arrangement across the benzimidazole plane, the N-substituents in 6 and 9 are arranged in a syn arrangement, which is a result of achieving optimum packing in the unit cell. Two of the carbon atoms (C29 and C30) in the alicyclic ring of the FPyr ligand in 5 were also disordered into two positions, with an occupancy ratio of 50:
50. The molecular structure of complex 11 is particularly interesting, in that two of the phenyl rings of the P(OPh)3 ligand are pointed towards the gold metal center. The remaining one is pointed away as a result of the close proximity of a PF6− anion. The potential steric shielding of the metal center accorded by the phenyl rings is unique to this ligand, and could prove beneficial for the overall stability of the complex. Furthermore, it is worth noting that none of the complexes showed evidence for intermolecular aurophilic interactions in the solid state.9
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Fig. 2 Molecular structures of complexes 5·CHCl3, 6, and 9–11 showing 50% probability ellipsoids; hydrogen atoms, PF6− anions, and solvent molecules (if any) are omitted for clarity. Selected bond lengths [Å] and angles [°]: 5·CHCl3: Au1–C1 2.017(5), Au1–C22 2.015(5); C1–Au1–C22 177.7(2); 6: Au1–C1 2.027(5), Au1–C16 2.013(5); C1–Au1–C16 174.85(19); 9: Au1–C1 2.020(3), Au1–C14 2.018(3); C1–Au1–C14 176.81(12); 10: Au1–C1 2.035(6), Au1–P1 2.2843(17); C1–Au1–P1 175.43(17); 11: Au1–C1 2.030(6), Au1–P1 2.2426(18); C1–Au1–P1 177.17(18). |
Considering the hetero-bis(carbene) complexes 3–9, it is noted that they do not perform as well as the previously reported complex 2, although 3 does come close with an IC50 value of 0.346 μM. Also, there seems to be no consistent relationship between the nature and length of the N-substituents on the benzimidazole-derived NHC and the activity of the complexes. However, it is worth noting that complexes 2 and 3, which both bear symmetrically substituted benzimidazole-derived NHCs, with both N-substituents being 2° carbon atoms, show superior performance as compared to complexes that bear benzimidazole-derived NHCs with either asymmetric N-substituents (i.e. complex 4), or 1° carbon atom N-substituents (i.e. complexes 5–9). This does suggest some form of structure–activity relationship, although further studies would be necessary to better understand the relative performance. Among the hetero-bis(carbene) complexes, 9 is an exception, and this may be attributed to the presence of reactive allyl moieties that make the complex more susceptible to addition and redox reactions, possibly degrading and/or deactivating the complex.
While the presence of a labile ligand seems necessary for the superior activity of these gold(I) complexes, it is apparently also important that the ligand trans to the FPyr ligand is not too weakly bound to the metal center. Evidence for this is found when considering complexes 10–12. As we progress from the stronger donating PPh3 to the much weaker donating DMAP, there is an increase in the IC50 values. Since the mode of action of other cationic gold–NHC complexes has been reported to involve permeation into the mitochondria,1,2,7 it is possible that in the case of complex 12, for example, the DMAP ligand detaches from the complex cation prematurely and prior to entering the mitochondria. This may potentially deactivate the compound even before it reaches its target site. Therefore, a fine balancing of these various properties seems necessary for the development of an optimum complex.
[Au(FPyr)((CHPh2)2-bimy)]PF6 (3). Yield: 82%. 1H NMR (500 MHz, CDCl3): δ 7.66 (s, 2 H, NCH), 7.40–7.38 (m, 12 H, Ar–H), 7.28–7.27 (m, 8 H, Ar–H), 7.17 (dd, 2 H, Ar–H), 7.05 (dd, 2 H, Ar–H), 4.02 (t, 2 H, 3J(H,H) = 5.70 Hz, NCH2), 3.88 (t, 2 H, 3J(H,H) = 5.70 Hz, NCH2), 2.56 (t, 2 H, 3J(H,H) = 6.30 Hz, CH2), 2.34 (t, 2 H, 3J(H,H) = 5.70 Hz, CH2), 2.12 (m, 2 H, CH2), 2.01 (m, 2 H, CH2), 1.82 (m, 2 H, CH2), 1.70 (m, 2 H, CH2). 13C{1H} NMR (125.8 MHz, CDCl3): δ 197.8 (Ccarbene ((CHPh2)2-bimy)), 178.8 (Ccarbene (FPyr)), 144.4, 137.9, 134.5, 129.7, 129.5, 129.0, 126.3, 125.3, 114.6 (Ar–C), 68.8 (NCH), 51.5, 46.5 (NCH2), 23.3, 22.9, 22.5, 21.9, 21.2, 21.0 (CH2). 31P{1H} NMR (202.4 MHz, CDCl3): δ −143.8 (m, PF6). 19F{1H} NMR (282.4 MHz, CDCl3): δ 2.30 (d, PF6). Anal. Calc. for C44H42N4AuPF6: C, 54.55; H, 4.37; N, 5.78. Found: C, 54.54; H, 4.26; N, 5.61%. MS (ESI): m/z = 823 [M − PF6]+.
[Au(FPyr)((iPr)(CHPh2)-bimy)]PF6 (4). Yield: 76%. 1H NMR (500 MHz, CDCl3): δ 7.73 (d, 1 H, Ar–H), 7.68 (s, 1 H, NCHPh2), 7.42–7.28 (m, 11 H, Ar–H), 7.22 (t, 1 H, Ar–H), 7.03 (d, 1 H, Ar–H), 5.40 (m, 1 H, 3J(H,H) = 6.30 Hz, NCH(CH3)2), 4.20 (br t, 2 H, NCH2), 4.09 (br t, 2 H, NCH2), 2.62 (br t, 2 H, CH2), 2.52 (br t, 2 H, CH2), 2.16 (br m, 4 H, CH2), 1.88 (d, 6 H, 3J(H,H) = 6.30 Hz, CH3), 1.77 (br m, 2 H, CH2), 1.31 (br m, 2 H, CH2). 13C{1H} NMR (125.8 MHz, CDCl3): δ 195.1 (Ccarbene ((iPr)(CHPh2)-bimy)), 179.2 (Ccarbene (FPyr)), 144.4, 138.0, 134.2, 133.4, 129.7, 129.6, 129.3, 129.0, 126.4, 125.13, 125.07, 114.6, 113.5 (Ar–C), 68.8 (NCHPh2), 54.0 (NCH(CH3)2), 51.7, 46.6 (NCH2), 23.31 (CH2), 23.29 (CH3), 23.0, 22.5, 21.9, 21.2, 21.0 (CH2). 31P{1H} NMR (202.4 MHz, CDCl3): δ −143.8 (m, PF6). 19F{1H} NMR (282.4 MHz, CDCl3): δ 2.34 (d, PF6). Anal. Calc. for C34H38N4AuPF6·0.3CH2Cl2·0.6Et2O: C, 48.20; H, 4.92; N, 6.13. Found: C, 48.29; H, 4.71; N, 6.01%. MS (ESI): m/z = 699 [M − PF6]+.
[Au(FPyr)((CH2Ph)2-bimy)]PF6 (5). Yield: 80%. 1H NMR (500 MHz, CDCl3): δ 7.44–7.31 (m, 14 H, Ar–H), 5.77 (s, 4 H, NCH2Ph), 4.22 (t, 2 H, 3J(H,H) = 5.70 Hz, NCH2), 4.03 (t, 2 H, 3J(H,H) = 5.70 Hz, NCH2), 2.57 (t, 2 H, 3J(H,H) = 6.30 Hz, CH2), 2.50 (t, 2 H, 3J(H,H) = 6.30 Hz, CH2), 2.09 (m, 4 H, CH2), 1.83 (m, 2 H, CH2), 1.72 (m, 2 H, CH2). 13C{1H} NMR (125.8 MHz, CDCl3): δ 195.7 (Ccarbene ((CH2Ph)2-bimy)), 179.9 (Ccarbene (FPyr)), 144.4, 135.8, 134.2, 129.8, 129.2, 127.9, 126.7, 125.6, 112.8 (Ar–C), 52.9 (NCH2Ph), 51.7, 46.6 (NCH2), 23.3, 22.9, 22.5, 21.9, 21.3, 21.1 (CH2). 31P{1H} NMR (202.4 MHz, CDCl3): δ −143.7 (m, PF6). 19F{1H} NMR (282.4 MHz, CDCl3): δ 2.59 (d, PF6). Anal. Calc. for C32H34N4AuPF6: C, 47.07; H, 4.20; N, 6.86. Found: C, 47.15; H, 4.25; N, 6.87%. MS (ESI): m/z = 671 [M − PF6]+.
[Au(FPyr)(iBu2-bimy)]PF6 (6). Yield: 74%. 1H NMR (500 MHz, CDCl3): δ 7.52 (dd, 2 H, Ar–H), 7.44 (dd, 2 H, Ar–H), 4.40 (br t, 2 H, NCH2), 4.31 (d, 4 H, 3J(H,H) = 7.55 Hz, NCH2CH(CH3)2), 4.10 (br t, 2 H, NCH2), 2.62 (t, 2 H, 3J(H,H) = 6.30 Hz, CH2), 2.59 (t, 2 H, 3J(H,H) = 6.30 Hz, CH2), 2.44 (m, 2 H, NCH2CH(CH3)2), 2.19 (br t, 4 H, CH2), 1.87 (m, 2 H, CH2), 1.79 (m, 2 H, CH2), 1.03 (d, 12 H, 3J(H,H) = 6.30 Hz, CH3). 13C{1H} NMR (125.8 MHz, CDCl3): δ 194.8 (Ccarbene (iBu2-bimy)), 180.2 (Ccarbene (FPyr)), 144.5, 134.3, 126.6, 125.3, 112.5 (Ar–C), 56.4 (NCH2CH(CH3)2), 51.8, 46.6 (NCH2), 30.2 (NCH2CH(CH3)2), 23.4, 23.0, 22.5, 22.0, 21.3, 21.1 (CH2), 21.0 (CH3). 31P{1H} NMR (202.4 MHz, CDCl3): δ −143.7 (m, PF6). 19F{1H} NMR (282.4 MHz, CDCl3): δ 2.49 (d, PF6). Anal. Calc. for C26H38N4AuPF6: C, 41.72; H, 5.12; N, 7.48. Found: C, 41.52; H, 5.10; N, 7.31%. MS (ESI): m/z = 603 [M − PF6]+.
[Au(FPyr)(n-Pr2-bimy)]PF6 (7). Yield: 79%. 1H NMR (500 MHz, CD3CN): δ 7.67 (dd, 2 H, Ar–H), 7.47 (dd, 2 H, Ar–H), 4.49 (t, 4 H, 3J(H,H) = 6.90 Hz, NCH2CH2CH3), 4.41 (br t, 2 H, NCH2), 4.04 (br t, 2 H, NCH2), 2.60 (m, 4 H, CH2), 2.10 (br t, 4 H, CH2), 1.99 (m, 4 H, CH2), 1.84 (m, 2 H, CH2), 1.76 (m, 2 H, CH2), 0.98 (t, 6 H, 3J(H,H) = 7.60 Hz, CH3). 13C{1H} NMR (125.8 MHz, CD3CN): δ 194.8 (Ccarbene (n-Pr2-bimy)), 180.0 (Ccarbene (FPyr)), 144.5, 134.2, 126.3, 125.1, 112.7 (Ar–C), 51.8 (NCH2), 50.6 (NCH2CH2CH3), 46.6 (NCH2), 24.2 (NCH2CH2CH3), 23.4, 22.8, 22.5, 21.7, 21.1, 20.8 (CH2), 11.5 (CH3). 31P{1H} NMR (202.4 MHz, CD3CN): δ −143.2 (m, PF6). 19F{1H} NMR (282.4 MHz, CD3CN): δ 3.43 (d, PF6). Anal. Calc. for C24H34N4AuPF6: C, 40.01; H, 4.76; N, 7.78. Found: C, 40.04; H, 4.40; N, 7.73%. MS (ESI): m/z = 575 [M − PF6]+.
[Au(FPyr)(Et2-bimy)]PF6 (8). Yield: 72%. 1H NMR (500 MHz, CDCl3): δ 7.53 (dd, 2 H, Ar–H), 7.46 (dd, 2 H, Ar–H), 4.57 (m, 4 H, 3J(H,H) = 7.55 Hz, NCH2CH3), 4.47 (t, 2 H, 3J(H,H) = 5.65 Hz, NCH2), 4.09 (t, 2 H, 3J(H,H) = 6.30 Hz, NCH2), 2.62 (t, 4 H, 3J(H,H) = 6.30 Hz, CH2), 2.21 (m, 4 H, CH2), 1.89 (m, 2 H, CH2), 1.80 (m, 2 H, CH2), 1.60 (t, 6 H, 3J(H,H) = 7.60 Hz, CH3). 13C{1H} NMR (125.8 MHz, CDCl3): δ 194.1 (Ccarbene (Et2-bimy)), 180.7 (Ccarbene (FPyr)), 144.3, 133.7, 126.7, 125.3, 112.1 (Ar–C), 52.0, 46.7 (NCH2), 44.4 (NCH2CH3), 23.4, 23.0, 22.6, 22.0, 21.4, 21.2 (CH2), 16.6 (CH3). 31P{1H} NMR (202.4 MHz, CDCl3): δ −143.8 (m, PF6). 19F{1H} NMR (282.4 MHz, CDCl3): δ 2.27 (d, PF6). Anal. Calc. for C22H30N4AuPF6: C, 38.16; H, 4.37; N, 8.09. Found: C, 38.38; H, 4.04; N, 8.09%. MS (ESI): m/z = 547 [M − PF6]+.
[Au(FPyr)((2-propenyl)2-bimy)]PF6 (9). Yield: 75%. 1H NMR (500 MHz, CD3CN): δ 7.63 (dd, 2 H, Ar–H), 7.47 (dd, 2 H, Ar–H), 6.14 (m, 2 H, NCH2CHCH2), 5.28 (dm, 2 H, 3J(H,H) = 10.10 Hz, NCH2CH
CHHtrans), 5.16–5.19 (m, 6 H, NCH2CH
CH2 and NCH2CH
CHHcis), 4.39 (t, 2 H, 3J(H,H) = 5.70 Hz, NCH2), 4.04 (t, 2 H, 3J(H,H) = 5.70 Hz, NCH2), 2.59 (m, 4 H, CH2), 2.09 (br t, 4 H, CH2), 1.84 (m, 2 H, CH2), 1.76 (m, 2 H, CH2). 13C{1H} NMR (125.8 MHz, CD3CN): δ 196.0 (Ccarbene ((2-propenyl)2-bimy)), 179.9 (Ccarbene (FPyr)), 144.7, 134.4, 133.7, 126.5, 125.6, 118.6, 113.1 (Ar–C and vinylic–C), 52.0 (NCH2), 51.5 (NCH2CH
CH2), 46.8 (NCH2), 23.6, 23.0, 22.7, 21.9, 21.3, 21.0 (CH2). 31P{1H} NMR (202.4 MHz, CD3CN): δ −144.0 (m, PF6). 19F{1H} NMR (282.4 MHz, CD3CN): δ 3.46 (d, PF6). Anal. Calc. for C24H30N4AuPF6: C, 40.23; H, 4.22; N, 7.82. Found: C, 40.14; H, 4.36; N, 7.64%. MS (ESI): m/z = 571 [M − PF6]+.
[Au(FPyr)(PPh3)]PF6 (10). Yield: 94%. 1H NMR (500 MHz, CDCl3): δ 7.54–7.41 (m, 15 H, Ar–H), 4.41 (br t, 2 H, NCH2), 4.12 (br t, 2 H, NCH2), 2.60 (m, 4 H, CH2), 2.18 (br m, 4 H, CH2), 1.86 (br m, 2 H, CH2), 1.77 (br m, 2 H, CH2). 13C{1H} NMR (125.8 MHz, CDCl3): δ 182.4 (Ccarbene), 144.7 (Ar–C), 134.6, 132.5, 130.1, 130.0 (d, Ar–C), 126.4 (Ar–C), 52.0, 46.7 (NCH2), 23.2, 22.9, 22.5, 21.8, 21.2, 20.9 (CH2). 31P{1H} NMR (202.4 MHz, CDCl3): δ 41.3 (PPh3), −143.8 (m, PF6). 19F{1H} NMR (282.4 MHz, CDCl3): δ 2.32 (d, PF6). Anal. Calc. for C29H31N2AuP2F6: C, 44.63; H, 4.00; N, 3.59. Found: C, 44.88; H, 3.89; N, 3.40%. MS (ESI): m/z = 635 [M − PF6]+.
[Au(FPyr)(P(OPh)3)]PF6 (11). Yield: 77%. 1H NMR (500 MHz, CDCl3): δ 7.48–7.27 (m, 15 H, Ar–H), 4.02 (t, 2 H, 3J(H,H) = 5.70 Hz, NCH2), 3.79 (t, 2 H, 3J(H,H) = 6.30 Hz, NCH2), 2.52 (t, 2 H, 3J(H,H) = 6.30 Hz, CH2), 2.20 (t, 2 H, 3J(H,H) = 6.30 Hz, CH2), 2.10 (m, 2 H, CH2), 2.00 (m, 2 H, CH2), 1.78 (m, 2 H, CH2), 1.65 (m, 2 H, CH2). 13C{1H} NMR (125.8 MHz, CDCl3): δ 179.6 (d, 2J(C,P) = 178 Hz, Ccarbene), 150.1, 144.6, 131.3, 127.5, 126.6, 121.9 (d, Ar–C), 51.5, 46.6 (NCH2), 23.1, 22.4, 22.3, 21.4, 21.2, 20.7 (CH2). 31P{1H} NMR (202.4 MHz, CDCl3): δ 139.3 (P(OPh)3), −143.8 (m, PF6). 19F{1H} NMR (282.4 MHz, CDCl3): δ 2.35 (d, PF6). Anal. Calc. for C29H31N2O3AuP2F6: C, 42.04; H, 3.77; N, 3.38. Found: C, 42.30; H, 3.77; N, 3.62%. MS (ESI): m/z = 683 [M − PF6]+.
[Au(FPyr)(DMAP)]PF6 (12). Yield: 81%. 1H NMR (500 MHz, CD3CN): δ 7.99 (d, 2 H, Ar–H), 6.68 (d, 2 H, Ar–H), 4.37 (br t, 2 H, NCH2), 4.00 (br t, 2 H, NCH2), 3.05 (s, 6 H, NCH3), 2.54 (m, 4 H, CH2), 2.06 (m, 4 H, CH2), 1.82 (br m, 2 H, CH2), 1.73 (br m, 2 H, CH2). 13C{1H} NMR (125.8 MHz, CD3CN): δ 161.0 (Ccarbene), 156.1, 150.4, 144.7, 125.9, 108.3 (Ar–C), 52.1, 46.7 (NCH2), 39.5 (NCH3), 23.3, 23.0, 22.5, 21.7, 21.1, 20.9 (CH2). 31P{1H} NMR (202.4 MHz, CD3CN): δ −143.1 (m, PF6). 19F{1H} NMR (282.4 MHz, CD3CN): δ 3.46 (d, PF6). Anal. Calc. for C18H26N4AuPF6: C, 33.76; H, 4.09; N, 8.75. Found: C, 33.85; H, 4.10; N, 8.51%. MS (ESI): m/z = 405 [M − PF6 − DMAP + CH3OH]+, 495 [M − PF6]+.
5·CHCl3 | 6 | 9 | 10 | 11 | |
---|---|---|---|---|---|
Formula | C33H35N4AuCl3PF6 | C26H38N4AuPF6 | C24H30N4AuPF6 | C29H31N2AuP2F6 | C29H31N2O3AuP2F6 |
fw | 935.94 | 748.54 | 716.46 | 780.46 | 828.46 |
Colour, habit | Colourless, block | Colourless, block | Colourless, block | Colourless, block | Colourless, block |
Crystal size (mm) | 0.13 × 0.11 × 0.04 | 0.27 × 0.11 × 0.05 | 0.36 × 0.26 × 0.10 | 0.28 × 0.08 × 0.06 | 0.17 × 0.11 × 0.08 |
Temp (K) | 100(2) | 100(2) | 100(2) | 100(2) | 100(2) |
Cryst syst | Triclinic | Triclinic | Triclinic | Orthorhombic | Orthorhombic |
Space group | P![]() | P![]() | P![]() | Pna21 | P212121 |
a (Å) | 8.5921(10) | 11.000(3) | 9.7407(7) | 20.319(4) | 10.5523(6) |
b (Å) | 11.9088(14) | 12.126(3) | 12.5859(9) | 13.683(3) | 14.9858(8) |
c (Å) | 17.348(2) | 12.426(3) | 12.8314(9) | 10.2795(19) | 19.0095(10) |
α (°) | 87.324(2) | 109.051(5) | 60.9630(10) | 90 | 90 |
β (°) | 87.300(2) | 98.373(5) | 73.3970(10) | 90 | 90 |
γ (°) | 80.596(2) | 108.802(5) | 68.0160(10) | 90 | 90 |
V (Å3) | 1747.9(4) | 1423.7(6) | 1264.80(16) | 2857.9(9) | 3006.1(3) |
Z | 2 | 2 | 2 | 4 | 4 |
Dc (g cm−3) | 1.778 | 1.746 | 1.881 | 1.814 | 1.831 |
Radiation used | Mo Kα | Mo Kα | Mo Kα | Mo Kα | Mo Kα |
μ (mm−1) | 4.546 | 5.285 | 5.944 | 5.321 | 5.072 |
θ (°) | 1.18–27.50 | 2.04–27.49 | 1.83–27.50 | 2.48–27.50 | 2.14–27.50 |
No. of unique data | 8012 | 6505 | 5813 | 6506 | 6905 |
Max, min transmission | 0.8391, 0.5895 | 0.7456, 0.5412 | 0.5879, 0.2234 | 0.7407, 0.3173 | 0.6871, 0.4793 |
Final R indices [I > 2σ(I)] | R1 = 0.0400, wR2 = 0.0890 | R1 = 0.0384, wR2 = 0.0850 | R1 = 0.0244, wR2 = 0.0622 | R1 = 0.0373, wR2 = 0.0764 | R1 = 0.0452, wR2 = 0.0847 |
R indices (all data) | R1 = 0.0469, wR2 = 0.1057 | R1 = 0.0449, wR2 = 0.0873 | R1 = 0.0263, wR2 = 0.0703 | R1 = 0.0494, wR2 = 0.0816 | R1 = 0.0514, wR2 = 0.0869 |
Goodness-of-fit on F2 | 1.132 | 1.068 | 1.266 | 0.973 | 1.004 |
Peak/hole (e Å−3) | 1.687/−2.077 | 2.285/−2.254 | 1.227/−0.647 | 2.555/−0.638 | 2.037/−1.176 |
Footnote |
† Electronic supplementary information (ESI) available: Dose–response curves for 3–12. CCDC 935297–935301. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3dt51071a |
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