Two RuII carbonyl complexes derived from 4,5-diazafluoren-9-one exhibit different modes of binding of this ligand and are of interest with regard to CO release in biological systems.
Keywords: metal–carbonyl complexes, bite distance, CO releasing molecules, ruthenium complexes, crystal structure, therapeutics, mode of binding, biological effect
Abstract
Carbon monoxide (CO) has recently been shown to impart beneficial effects in mammalian physiology and considerable research attention is now being directed toward metal–carbonyl complexes as a means of delivering CO to biological targets. Two ruthenium carbonyl complexes, namely trans-dicarbonyldichlorido(4,5-diazafluoren-9-one-κ2 N,N′)ruthenium(II), [RuCl2(C11H6N2O)(CO)2], (1), and fac-tricarbonyldichlorido(4,5-diazafluoren-9-one-κN)ruthenium(II), [RuCl2(C11H6N2O)(CO)3], (2), have been isolated and structurally characterized. In the case of complex (1), the trans-directing effect of the CO ligands allows bidentate coordination of the 4,5-diazafluoren-9-one (dafo) ligand despite a larger bite distance between the N-donor atoms. In complex (2), the cis disposition of two chloride ligands restricts the ability of the dafo molecule to bind ruthenium in a bidentate fashion. Both complexes exhibit well defined 1H NMR spectra confirming the diamagnetic ground state of RuII and display a strong absorption band around 300 nm in the UV.
Introduction
Carbon monoxide (CO) has recently been shown to impart salutary effects in mammalian physiology when applied in lower concentrations (Motterlini & Otterbien, 2010 ▸). This surprising discovery has raised interest in metal–carbonyl complexes as potential CO donors. Although metal–carbonyl complexes have been studied extensively for their photophysical and photochemical properties (Stufkens & Vlcek, 1998 ▸), considerable research attention has now been directed toward these species as a means of delivering CO to biological targets under controlled conditions as opposed to its administration in the gaseous form (Bernardes & Garcia-Gallego, 2014 ▸; Romao et al., 2012 ▸). In such attempts, the photoactive CO-releasing molecules (photoCORMs) have emerged as promising therapeutics where CO release can be triggered upon illumination (Gonzalez & Mascharak, 2014 ▸; Chakraborty et al., 2014 ▸; Schatzschneider, 2015 ▸). Herein we report the syntheses, properties and X-ray structures of two ruthenium carbonyl complexes, namely trans-[RuCl2(dafo)(CO)2], (1), and fac-[RuCl2(CO)3(dafo)(CO)3], (2), where dafo is 4,5-diazafluoren-9-one. The potentially bidentate ligand dafo binds the RuII center of (1) and (2) in a bidentate and a monodentate fashion, respectively. Both steric and electronic effects play concurrent roles in dictating the mode of binding of dafo in these two complexes.
Experimental
All reagents were of commercial grade and were used without further purification. The solvents were purified according to a standard procedure (Armarego & Chai, 2003 ▸). 4,5-Diazafluoren-9-one (dafo) was synthesized according to a reported procedure (Eckhard & Summers, 1973 ▸). A PerkinElmer Spectrum-One FT–IR spectrophotometer was employed to monitor the IR spectra of the compounds. UV–Vis spectra were obtained with a Varian Cary 50 UV–Vis spectrophotometer. 1H NMR spectra were recorded at 298 K on a Varian Unity Inova 500 MHz instrument. Microanalyses were carried out with a PerkinElmer Series II Elemental Analyzer.
Synthesis and crystallization
Synthesis of complex (1)
A slurry of [RuCl2(CO)3]2 (100 mg, 0.195 mmol) in dry methanol (15 ml) was heated under reflux (338 K) while stirring for 3 h. Next, 4,5-diazafluoren-9-one (dafo; 71.1 mg, 0.370 mmol) was added and the reaction mixture was allowed to reflux for an additional 3 h. The color of the solution changed from pale yellow to bright yellow during this time. Upon cooling, a yellow precipitate was observed which was filtetred off, washed with a minimum amount of CH2Cl2, and dried under reduced pressure (yield 72.8 mg, 48%). Elemental analysis (%) found: C 38.11, N 6.89, H 1.52; calculated for C13H6Cl2N2O3Ru: C 38.06, N 6.83, H 1.47. IR: ν(CO) (KBr, cm−1) 2078, 1993. 1H NMR (CDCl3): δ 8.96 (d, 2H), 8.24 (d, 2H), 7.73 (t, 2H).
Synthesis of complex (2)
A batch of [RuCl2(CO)3]2 (100 mg, 0.195 mmol) in dry methanol (20 ml) was allowed to stir at 318 K for 3 h. Next, dafo (71.2 mg, 0.370 mmol) was added and the solution was allowed to stir at 318 K for an additional 3 h. The white precipitate that formed during this time was filtered off, washed with a small amount of CH2Cl2, and dried under vacuum (yield 90.9 mg, 56%). Elemental analysis (%) found: C 38.42, N 6.43, H 1.43; calculated for C14H6Cl2N2O4Ru: C 38.37, N 6.39, H 1.38. IR: ν (CO) (KBr, cm−1) 2062, 1998. 1H NMR (CDCl3): δ 9.70 (d, 1H), 8.76 (d, 1H), 8.20 (d, 1H), 8.15 (d, 1H), 7.70 (d, 1H), 7.62 (t, 1H).
Isolation of complexes (1) and (2)
Single crystals of both complexes were obtained by layering hexanes over their CH2Cl2 solutions. One crystal of each complex was selected and fixed on top of MiTiGen micromounts using Paratone Oil and tranferred to the diffractometer.
Refinement
Crystal data, data collection and structure refinement details are summarized in Table 1 ▸. The metal atoms were located by direct methods and the remaining non-H atoms emerged from successive Fourier syntheses. H atoms were included in calculated positions riding on the C atom to which they are bonded, with C—H = 0.93 Å and U iso(H) = 1.2U eq(C). Carbonyl atoms C1 and O1 in (2) were constrained to have equivalent atomic displacement parameters and the C6—C7 bond was restrained to emulate rigid-body motion.
Table 1. Experimental details.
| (1) | (2) | |
|---|---|---|
| Crystal data | ||
| Chemical formula | [RuCl2(C11H6N2O)(CO)2] | [RuCl2(C11H6N2O)(CO)3] |
| M r | 410.17 | 438.18 |
| Crystal system, space group | Monoclinic, P21/n | Triclinic, P
|
| Temperature (K) | 296 | 296 |
| a, b, c () | 6.5589(2), 16.9199(6), 12.7585(5) | 7.458(2), 9.701(2), 11.594(9) |
| , , () | 90, 100.69, 90 | 90.43(3), 108.60(4), 98.41(2) |
| V (3) | 1391.30(8) | 785.1(7) |
| Z | 4 | 2 |
| Radiation type | Mo K | Mo K |
| (mm1) | 1.52 | 1.36 |
| Crystal size (mm) | 0.20 0.15 0.12 | 0.15 0.10 0.08 |
| Data collection | ||
| Diffractometer | Bruker APEXII CCD diffractometer | Bruker APEXII CCD diffractometer |
| Absorption correction | Multi-scan (SADABS; Bruker, 2008 ▸) | Multi-scan (SADABS; Bruker, 2008 ▸) |
| T min, T max | 0.668, 0.745 | 0.682, 0.745 |
| No. of measured, independent and observed [I > 2(I)] reflections | 13644, 2840, 2598 | 7433, 2934, 2141 |
| R int | 0.055 | 0.049 |
| (sin /)max (1) | 0.625 | 0.609 |
| Refinement | ||
| R[F 2 > 2(F 2)], wR(F 2), S | 0.029, 0.076, 1.01 | 0.037, 0.060, 1.13 |
| No. of reflections | 2840 | 2934 |
| No. of parameters | 190 | 202 |
| No. of restraints | 0 | 1 |
| H-atom treatment | H-atom parameters constrained | H-atom parameters constrained |
| max, min (e 3) | 1.02, 0.42 | 0.74, 0.60 |
Results and discussion
The complexes trans-[RuCl2(dafo)(CO)2] (dafo is 4,5-diazafluoren-9-one), (1), and fac-[RuCl2(dafo)(CO)3], (2), were isolated from the reaction of [RuCl2(CO)3]2 with two equivalents of dafo in methanol. Complex (1) was isolated from the methanolic reaction mixture under refluxing conditions. Quite in contrast, stirring of the reaction mixture in methanol at 318 K resulted in (2). In accordance with our previous report on cis- and trans-[RuCl2(azpy)(CO)2] [where azpy is 2-(phenyldiazenyl)pyridine] complexes (Carrington et al., 2013 ▸), warming of [RuCl2(CO)3]2 at 318 K presumably resulted in the intermediate solvento species fac-[RuCl2(MeOH)(CO)3]. Addition of dafo displaced the solvent molecule to furnish complex (2), where the dafo ligand binds the RuII center in a monodentate fashion. This finding is unusual compared to that observed for other analogous carbonyl complexes derived from rigid heterocycles like bipyridine (bpy), where, under similar conditions, the complex isolated is of formula cis-[RuCl2(bpy)(CO)2] (Haukka et al., 1995 ▸). In the case of complex (2), the relatively larger bite distance between the two N atoms of the dafo ligand (compared to bpy) most likely restricts bidentate coordination to the metal center (Pal et al., 2014 ▸). In the case of (1), the intermediate species fac-[RuCl2(MeOH)(CO)3] undergoes a facial→meridional isomerization upon refluxing (338 K). In this meridional intermediate, the trans disposition of two of the CO ligands facilitates removal of one CO ligand. This vacancy finally allows binding of the dafo ligand in a bidenate fashion in (1).
The coordination geometry of RuII in both complexes is distorted octahedral (Tables 2 ▸ and 3 ▸). The two CO ligands are cis to each other in complex (1) (Fig. 1 ▸), while in complex (2) (Fig. 2 ▸), the three CO ligands are arranged in a facial disposition. The two Cl− ligands are in trans and cis dispositions in (1) and (2), respectively. In complex (1), the chelate ring composed of atoms Ru1, N1, C7, C9, and N2 is almost planar, with a mean deviation of 0.007 (3) Å. The equatorial plane of (1) is comprised of the bidentate dafo ligand and two CO ligands (atoms C1, C2, N2, and N1), with a mean deviation of 0.040 (3) Å, and the RuII atom is displaced by 0.010 (3) Å towards the Cl2 atom. The coordinated dafo ligand is planar [mean deviation = 0.020 (3) Å] in complex (1). In the case of complex (2), the equatorial plane is comprised of one N atom of the monodentate dafo ligand, one chloride and two CO ligands (atoms N1, Cl2, C1, and C3), with a mean deviation of 0.034 (4) Å. The RuII atom is displaced by 0.059 (4) Å towards the carbonyl C2 atom. In this case, the dafo ligand frame is also fairly planar, with a mean deviation of 0.028 (3) Å. The monodentate dafo ligand in (2) forms a dihedral angle of 52.16 (8)° with the equatorial plane constitued by atoms C1, C3, N1, and Cl2. The crystal packing (Dolomanov et al., 2009 ▸; Spek, 2009 ▸) for the complexes reveal no significant stacking or other nonbonded interactions (Figs. 3 ▸ and 4 ▸). The distances between the two N atoms (N1 and N2) of the dafo ligand in (1) and (2) are 2.833 (4) and 3.146 (5) Å, respectively, due to the different modes of binding. The bidenate coordination of dafo in (1) appears to promote pronounced competition in π back-bonding between the dafo and CO ligands for the same metal orbitals compared to complex (2). This is corroborated by the apparent CO release rate (k CO) values of these complexes. In CH2Cl2 solution under 305 nm UV illumination, complex (1) exhibits a much higher k CO value (15.34±0.02 min−1, conc. 2.4 × 10−4 M) compared to complex (2) (6.08±0.02 min−1, conc. 2.4 × 10−4 M).
Table 2. Selected geometric parameters (, ) for (1) .
| Ru1C2 | 1.879(3) | Ru1N1 | 2.203(2) |
| Ru1C1 | 1.923(3) | Ru1Cl2 | 2.3844(9) |
| Ru1N2 | 2.161(2) | Ru1Cl1 | 2.3974(8) |
| C2Ru1C1 | 90.05(13) | N2Ru1Cl2 | 84.47(6) |
| C2Ru1N2 | 95.24(10) | N1Ru1Cl2 | 89.61(6) |
| C1Ru1N2 | 174.48(11) | C2Ru1Cl1 | 88.54(9) |
| C2Ru1N1 | 175.16(10) | C1Ru1Cl1 | 94.06(10) |
| C1Ru1N1 | 93.90(11) | N2Ru1Cl1 | 87.65(6) |
| N2Ru1N1 | 80.89(8) | N1Ru1Cl1 | 88.39(6) |
| C2Ru1Cl2 | 92.93(9) | Cl2Ru1Cl1 | 172.08(3) |
| C1Ru1Cl2 | 93.72(10) |
Table 3. Selected geometric parameters (, ) for (2) .
| Ru1C1 | 1.865(5) | Ru1N1 | 2.168(3) |
| Ru1C3 | 1.882(5) | Ru1Cl2 | 2.4037(16) |
| Ru1C2 | 1.914(4) | Ru1Cl1 | 2.4128(12) |
| C1Ru1C3 | 93.5(2) | C2Ru1Cl2 | 86.04(12) |
| C1Ru1C2 | 89.90(18) | N1Ru1Cl2 | 88.62(10) |
| C3Ru1C2 | 95.34(16) | C1Ru1Cl1 | 85.99(15) |
| C1Ru1N1 | 173.34(18) | C3Ru1Cl1 | 86.50(12) |
| C3Ru1N1 | 90.43(15) | C2Ru1Cl1 | 175.60(11) |
| C2Ru1N1 | 95.11(13) | N1Ru1Cl1 | 88.86(9) |
| C1Ru1Cl2 | 87.35(18) | Cl2Ru1Cl1 | 92.18(5) |
| C3Ru1Cl2 | 178.40(13) |
Figure 1.
A perspective view of complex (1), showing the atom labeling. Displacement ellipsoids are drawn at the 50% probability level.
Figure 2.
A perspective view of complex (2), showing the atom labeling. Displacement ellipsoids are drawn at the 50% probability level.
Figure 3.
The crystal packing of complex (1), showing a view along the b axis.
Figure 4.
The crystal packing of complex (2), showing a view along the b axis.
Supplementary Material
Crystal structure: contains datablock(s) 1, 2, global. DOI: 10.1107/S2053229615018100/ov3067sup1.cif
Structure factors: contains datablock(s) 1. DOI: 10.1107/S2053229615018100/ov30671sup2.hkl
Structure factors: contains datablock(s) 2. DOI: 10.1107/S2053229615018100/ov30672sup3.hkl
Acknowledgments
Financial support from NSF grant DMR-1409335 is gratefully acknowledged. JJ is supported by NIH grant 2R25GM058903.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Crystal structure: contains datablock(s) 1, 2, global. DOI: 10.1107/S2053229615018100/ov3067sup1.cif
Structure factors: contains datablock(s) 1. DOI: 10.1107/S2053229615018100/ov30671sup2.hkl
Structure factors: contains datablock(s) 2. DOI: 10.1107/S2053229615018100/ov30672sup3.hkl