Cytotoxic Activity of Some Half‐sandwich Rhodium(III) Complexes Containing 4,4’‐disubstituted‐2,2’‐bipyridine Ligands

{"full_text": " Journal of Inorganic and General Chemistry\n\n\n www.zaac.wiley-vch.de RESEARCH ARTICLE\nZeitschrift f\u00fcr anorganische und allgemeine Chemie\n\n\n\n DOI: 10.1002/zaac.202300195\n\n\n Cytotoxic Activity of Some Half-sandwich Rhodium(III)\n Complexes Containing 4,4\u2019-disubstituted-2,2\u2019-bipyridine\n Ligands\n Marion Graf,[a] Jasmine Ochs,[b] Peter Mayer,[a] Nils Metzler-Nolte,[b] and\n Hans-Christian B\u00f6ttcher*[a]\n Dedicated to Professor Ingo-Peter Lorenz on the occasion of his 80th birthday\n\n\n\n The synthesis and characterization of three compounds [Rh(\u03b75- determined by a single-crystal X-ray diffraction study. The\n C5Me5)Cl(N^N)]PF6 (N^N = 4,4\u2019-disubstituted-2,2\u2019-bipyridines, 1\u2013 cytotoxicity of all three compounds was examined by MTT assay\n 3) are described. The cationic complexes contain the bidentate against two cancer cell lines \u2013 HT-29 (colon adenocarcinoma)\n ligands N^N = 4,4'-di-tert-butyl-2,2'-bipyridine (1), N^N = 4,4'- and MCF-7 (human breast adenocarcinoma) - and normal\n dinonyl-2,2'-bipyridine (2) and N^N = 4,4'-diamino-2,2'-bipyri- human fibroblast cells (GM5657T). Compound 1 has moderate\n dine (3). The complex salts were obtained by the bridge- cytotoxicity against both cell lines, while compound 2 is seven\n splitting reaction from the precursor [{Rh(\u03b75-C5Me5)(\u03bc-Cl)Cl}2] to nine times more cytotoxic than cisplatin against MCF-7 and\n and subsequent salt metathesis affording their corresponding HT-29, respectively. In contrast to cisplatin, both compounds\n hexafluorido phosphate salts. All compounds were character- are more active against cancer cells than fibroblasts, thus\n ized by elemental analysis and spectroscopic means. Addition- showing some cancer selectivity.\n ally, the molecular structure of compound 3 in the solid was\n\n\n Introduction last years, e. g.[5\u201312] Especially rhodium complexes as therapeutic\n agents were of interest in this field because they exhibit a\n The immense clinical success of cisplatin and its derivatives has greater kinetical lability in comparison with its iridium\n inspired scientists to search for other transition metal com- congeners.[13] Recently, a review article summarized half-\n pounds playing a more significant role with respect to human sandwich rhodium(III) complexes covering the most important\n cancer therapy. In this light, targeting and drug resistance are results on their biological activities in light of their use as\n still great problems which need to be solved for an effective possible anticancer agents.[14] Thus many rhodium(III) com-\n transfer of novel metal complexes into clinical applications, plexes show higher in vitro activity and different mechanism of\n e. g.[1\u20134] Considering organometallic transition metal compounds action (MoA) in comparison to conventional anticancer metal-\n within the group of the other platinum elements, half-sandwich lodrugs (frequently cisplatin and derivatives thereof) or clinically\n complexes have received more attention in this light during the studied ruthenium-based drug candidates (NAMI-A and related\n Ru complexes). Moreover, many organometallic rhodium(III)\n complexes showed the highest anticancer activities in compar-\n [a] M. Graf, P. Mayer, Prof. Dr. H.-C. B\u00f6ttcher\n ison with their ruthenium, osmium and iridium analogues.[14]\n Department Chemie\n Ludwig-Maximilians-Universit\u00e4t Whereas our research interests were focused over many years\n Butenandtstrasse 5\u201313 (D) on octahedral bis-cyclometallated M(III) complexes (M = Rh, Ir)\n 81377 M\u00fcnchen, Germany bearing modified phenanthroline (phen) or related bipyridine\n Fax: + 49-89-2180-77407 (bpy) ligands in light of their evaluation as promising anticancer\n E-mail: hans.boettcher@cup.uni-muenchen.de agents,[15] we examined recently the cytotoxic activities of some\n [b] J. Ochs, N. Metzler-Nolte\n half-sandwich iridium(III) complexes containing 4,4'-disubsti-\n Faculty for Chemistry and Biochemistry\n Chair of Inorganic Chemistry I \u2013 Bioinorganic Chemistry tuted-2,2'-bipyridine ligands,[16] and related M(III) complexes\n Ruhr University Bochum (M = Rh and Ir) bearing chloro-substituted bidentate-coordi-\n Universit\u00e4tsstrasse 150 nated phenanthroline or terpyridine ligands.[17] To continue our\n 44801 Bochum, Germany efforts in this field we describe herein the synthesis and the\n Supporting information for this article is available on the WWW characterization of three rhodium(III) half-sandwich complexes\n under https://doi.org/10.1002/zaac.202300195 containing 4,4'-disubstituted-2,2'-bipyridine ligands including\n \u00a9 2023 The Authors. Zeitschrift f\u00fcr anorganische und allgemeine the evaluation of their cytotoxic activities towards the two\n Chemie published by Wiley-VCH GmbH. This is an open access\n prominent cancer cell lines HT-29 and MCF-7 respectively.\n article under the terms of the Creative Commons Attribution Non-\n Commercial License, which permits use, distribution and During these investigations, the molecular structure of the new\n reproduction in any medium, provided the original work is compound [Rh(\u03b75-C5Me5)Cl(N^N)]PF6 (N^N = 4,4'-diamino-2,2'-\n properly cited and is not used for commercial purposes.\n\n Z. Anorg. Allg. Chem. 2023, 649, e202300195 (1 of 5) \u00a9 2023 The Authors. Zeitschrift f\u00fcr anorganische und allgemeine Chemie published by Wiley-VCH GmbH\n\f Journal of Inorganic and General Chemistry\n\n\n\n\n 15213749, 2024, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/zaac.202300195 by Lomonosov Moscow State University, Wiley Online Library on [12/05/2026]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License\n RESEARCH ARTICLE\nZeitschrift f\u00fcr anorganische und allgemeine Chemie\n\n\n\n bipyridine, 3) in the solid was determined and confirmed by a these ring protons at \u03b4 = 8.62 (d, JHH = 5.6 Hz, 2H), 8.01 (d, JHH =\n single-crystal X-ray diffraction study. 1.6 Hz, 2H), and 7.55 (dd, JHH = 5.6 Hz, JHH = 1.6 Hz, 2H). These\n data are comparable to the observed ones of our compound 1\n and the related species described in the literature.[19] In the 13C\n Results and Discussion {1H} NMR spectrum (CD2Cl2) of 2 the characteristic resonance\n according to the \u03b75-C5Me5-ligand coordinated to rhodium was\n The preparation of the title compounds was realized using the found at 97.0 ppm with the coupling JRhC = 7.6 Hz. Similar data\n well-known literature method by cleavage of the precursor were observed also for compound 3 (for more details see\n [{Rh(\u03b75-C5Me5)(\u03bc-Cl)Cl}2] by addition of the corresponding Experimental Section). It should be noted that a closely related\n bidentate chelating ligands in methanol at ambient temper- compound to 3 was recently reported in the literature. Thus the\n ature with stirring for one hour.[18] The salt metathesis using same complex cation was described as the corresponding\n KPF6 afforded finally the products 1\u20133 from the intermediate chloride salt [Rh(\u03b75-C5Me5)Cl(4,4'-NH2-bpy)]Cl (obtained as\n formed chloride compounds (see Eq. 1 and Scheme 1 respec- dihydrate).[20] That compound was studied as a catalyst, beside\n tively). other related type of complexes, dealing with the hydrogen\n evolution during photoreduction studies of carbon dioxide to\n \u00bdfRh\u00f0h5 -C5 Me5 \u00de\u00f0m-Cl\u00deClg2 \ufffd \u00fe 2 N^N \u00fe 2 KPF6 ! formic acid. The reported NMR data of the latter species match\n well the collected ones for our compound 3. For example, the\n 2 \u00bdRh\u00f0h5 -C5 Me5 \u00deCl\u00f0N^N\u00de\ufffdPF6 \u00fe 2 KCl (1) following 13C{1H} NMR data for [Rh(\u03b75-C5Me5)Cl(4,4'-NH2-bpy)]Cl\n 1 3 recorded in dmso-d6 were reported: 157.0, 154.8, 151.2, 112.3,\n 106.4 and 95.6 (d, JRhC = 7.5 Hz). The signal corresponding to the\n (N^N = 4,4\u2019-disubstituted-2,2\u2019-bipyridines) carbon atoms of the methyl groups of the pentameth-\n Compounds 1\u20133 were obtained in yields ranging from 48 to ylcyclopentadienyl ligand resonated at 8.9 ppm.[20] (For compar-\n 69 % and fully characterized by elemental analysis, 1H, 13C{1H} ison purposes to compound 3 see Experimental Section.)\n NMR spectroscopy as well as by mass spectrometry. Addition-\n ally, the molecular structure of compound 3 in the crystal was\n confirmed by a single-crystal X-ray diffraction study (see below). Molecular Structure of Compound 3\n Whereas the compound 1 was already reported in the\n literature,[19] compounds 2 and 3 are newly reported species. As mentioned before, the molecular structure of compound 1\n The NMR data of our compound 1 are in very good agreement was already reported in the literature.[19] Considering compound\n with the corresponding reported ones for that species.[19] Thus, 2, unfortunately we were unable to grow suitable single-crystals\n some NMR spectroscopic data of the new compounds 2 and 3 of that compound to confirm its molecular structure in the\n should be discussed here shortly. Compound 2 exhibits in the crystal. Contrary, suitable single-crystals of compound 3 were\n 1\n H NMR spectrum (CD2Cl2) at room temperature resonances in grown by the layering method from dichloromethane solution\n the characteristic region of aromatic protons corresponding to using methanol/iso-hexane as the antisolvent at ambient\n temperature. The crystals were examined by X-ray diffraction\n and the result of the molecular structure determination of the\n complex cation of 3 is shown in Figure 1. Selected bond lengths\n are given in the figure caption.\n The complex cation of 3 exhibits the expected half-\n sandwich pseudo-octahedral \u201cthree-legged piano-stool\u201d geom-\n etry. Many related molecular structures were reported in the\n literature exhibiting such a rhodium backbone with the \u03b75-\n pentamethylcyclopentadienyl group and one chlorido ligand\n beside the bidentate N-donor ligand. For example, in the\n compound [Rh(\u03b75-C5Me5)Cl(N^N)]BF4 (N^N = Ph-terpy)[21] the\n corresponding bonding parameters comparable to 3 were\n found: Rh1 N1, 2.086(3); Rh1 N2, 2.197(3) and Rh Cl,\n 2.3984(1) \u00c5. Furthermore, for [Rh(\u03b75-C5Me5)Cl(phen)]ClO4 the\n bond lengths Rh1 N1, 2.128(3); Rh1 N2, 2.109(3) and Rh Cl,\n 2.386(1) \u00c5 were reported,[22] and for the complex [Rh2(\u03b75-\n C5Me5)2Cl2(\u03bc-bpym)]2 + (bpym = 2,2'-bipyrimidine) the corre-\n sponding data were Rh1 N1, 2.134(5); Rh1 N2, 2.161(5) and\n Rh Cl, 2.405(2) \u00c5.[23] Finally, the observed bonding parameters\n of 3 are also in accordance with the observed ones for the\n closely related cationic complex [Rh(\u03b75-C5Me5)Cl(4,7-dichloro-\n Scheme 1. General structure of compounds 1\u20133 (R = tBu, 1; R = non- 1,10-phenanthroline)] + : Rh1 N1, 2.1241(17); Rh1 N2, 2.1165(17)\n yl, 2; R = NH2, 3). and Rh1 Cl, 2.405(2) \u00c5,[17] as well as for [Rh(\u03b75-C5Me5)Cl(k2-N-\n\n Z. Anorg. Allg. Chem. 2023, 649, e202300195 (2 of 5) \u00a9 2023 The Authors. Zeitschrift f\u00fcr anorganische und allgemeine Chemie published by Wiley-VCH GmbH\n\f Journal of Inorganic and General Chemistry\n\n\n\n\n 15213749, 2024, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/zaac.202300195 by Lomonosov Moscow State University, Wiley Online Library on [12/05/2026]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License\n RESEARCH ARTICLE\nZeitschrift f\u00fcr anorganische und allgemeine Chemie\n\n\n\n Table 1. IC50 values in \u03bcM of 1\u20133 for the antiproliferative activity\n towards MCF-7 and HT-29 cells. MTT assay, 48 h incubation time,\n total concentration of DMSO was 0.5 % in all samples including\n cisplatin control. Results are mean values of three independent\n measurements, + / standard deviation.\n compound MCF-7 HT-29 GM5657T\n 1 69.4 \ufffd 3.2 59.7 \ufffd 2.6 160.9 \ufffd 15.5\n 2 7.1 \ufffd 1.5 10.4 \ufffd 0.5 21.0 \ufffd 0.9\n 3 > 250 > 250 > 250\n Cisplatin 48.9 \ufffd 8.8 94.3 \ufffd 12.3 19.7 \ufffd 4.5\n\n\n\n\n bpy complex [Rh(\u03b75-C5Me5)Cl(bpy)]Cl, published by Sheldrick\n and co-workers, shows no cytotoxicity against MCF-7 and HT-29\n up to 100 \u03bcM. The complex undergoes a Cl /water exchange,[26]\n typical for complexes bearing the RhIII(\u03b75-C5Me5)Cl backbone.[18]\n Figure 1. The molecular structure of the cationic complex of The formed dicationic species is only marginally taken up by\n compound 3 in the crystal (ORTEP drawing and atom labeling cells, leading to low activity.[27] Therefore, we tested the stability\n scheme with 25 % probability level). Solvent molecules are omitted\n of our complexes in water/DMSO, simulating our assay\n for clarity. Selected bond lengths/\u00c5: Rh1 N1, 2.094(3); Rh1 N2,\n 2.087(3); Rh1 Cl, 2.4281(8). conditions. The stability was monitored by 1H NMR spectro-\n scopy, recording spectra between 5 minutes to 72 hours after\n dissolution (compare the ESI of this article). During this time,\n neither the compound signals changed nor an additional,\n tppz)] + : Rh1 N1, 2.1418(19); Rh1 N2, 2.1245(18) and Rh1 Cl, shifted water or DMSO signal appeared. As compounds 1\u20133\n 2.4127(6) \u00c5 [tppz = 2,3,5,6-tetra(2'-pyridyl)pyrazine] reported by behave similarly, the difference in activity needs to arise from\n us recently.[24] the residues. For larger aromatic systems, the uptake and\n cytotoxicity are improved by increasing the \u03c0-system, but the\n addition of charged groups leads to activity loss.[27] This\n Biological Activity of Compounds 1\u20133 observation fits our findings that NH2 derivatization (3, proto-\n nated under physiological conditions) leads to activity loss,\n Sadler and co-workers investigated numerous organometallic while the alkyl chains tBu (1) and nonyl (2) show moderate and\n rhodium complexes of the general type [Rh(\u03b75-C5Me5)Cl(N^N)] + good activity, respectively.\n as anticancer agents especially in light of C H bond activation As anticancer drugs should be selective towards cancer\n on the methyl groups.[25] They showed that a new activation cells, cytotoxicity was tested additionally against normal human\n mechanism is possible and facile for certain rhodium(III) cyclo- fibroblast cells (GM5657T). Here, the approved drug cisplatin is\n pentadienyl complexes containing chelated \u03c0-acceptor diamine two to five times more toxic against GM5657T than against\n ligands such as bpy or phen. These findings inspired us to MCF-7 or HT-29, respectively. This finding is in agreement with\n investigate the compounds 1\u20133 with respect to their biological the known and massive side effects of cisplatin treatment. In\n activity. For this reason, the antiproliferative activity of the three contrast, our active compounds 1 and 2 show improved\n complexes towards the cancer cell lines MCF-7 (human breast selectivity towards cancer cells as they are two times more\n adenocarcinoma) and HT-29 (colon adenocarcinoma) has been active against both tested cell lines than against the non-\n determined. In addition, selectivity towards cancer cells was cancerous human fibroblast cells. As noted before, compound 3\n checked against normal human fibroblasts cells (GM5657T). The is not active against all tested cell lines.\n cytotoxicity was evaluated using the MTT assay, which meas-\n ures the mitochondrial metabolism in the entire cell. The\n resulting IC50 values are shown in Table 1. Conclusions\n The antiproliferative activity shows a significant difference\n between the three complexes. Complex 3, which is diamino- The synthesis and the characterization of three rhodium\n substituted in the 4,4'-position, is not active. However, complex compounds of the type [Rh(\u03b75-C5Me5)Cl(N^N)]PF6 (N^N = 4,4\u2019-\n 1, bearing tert-butyl groups in 4,4'-position, shows moderate disubstituted-2,2\u2019-bipyridines, 1\u20133) were described. During\n cytotoxicity against MCF-7 and HT-29 cancer cells with 69.4 \u03bcM these investigations the molecular structure of compound 3\n and 59.7 \u03bcM, respectively. In contrast, complex 2, with the large was determined by an X-ray diffraction study. The antiprolifer-\n nonyl groups, has IC50 values about six times lower than ative activity of complex 1 is moderate against the MCF-7 and\n complex 1. Moreover, the cytotoxicity of 2 is significantly HT-29 cancer cell lines, while 2 shows promising activity in the\n improved compared to cisplatin, with 7.1 \u03bcM against MCF-7 low \u03bcM range. Unlike the established anticancer drug cisplatin,\n and 10.4 \u03bcM against HT-29. In comparison, the non-derivatized both compounds show some selectivity towards cancer cells\n\n Z. Anorg. Allg. Chem. 2023, 649, e202300195 (3 of 5) \u00a9 2023 The Authors. Zeitschrift f\u00fcr anorganische und allgemeine Chemie published by Wiley-VCH GmbH\n\f Journal of Inorganic and General Chemistry\n\n\n\n\n 15213749, 2024, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/zaac.202300195 by Lomonosov Moscow State University, Wiley Online Library on [12/05/2026]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License\n RESEARCH ARTICLE\nZeitschrift f\u00fcr anorganische und allgemeine Chemie\n\n\n\n over normal, non-cancerous cells like human fibroblasts. It can [Rh(\u03b75-C5Me5)Cl(4,4'-(But)2-2,2'-bpy)]PF6 (1): Yield: 110 mg (53.4 %).\n be speculated that an increased lipophilicity of 2 leads to higher Anal. C28H39ClF6N2PRh (686.95): calcd. C, 48.96; H, 5.72; N, 4.08.\n cell uptake, and hence higher activity of the compound. This is Found: C, 48.71; H, 5.98; N, 3.89 %. MS (FAB +): m/z = 541.2 [M + ]\n complex cation. 1H NMR (400 MHz, CD2Cl2): \u03b4 = 8.67 (d, JHH = 6.0 Hz,\n also in line with the observation that the amino-substituted 2H), 8.11 (d, JHH = 2.0 Hz, 2H), 7.74 (dd, JHH = 6.0 Hz, JHH = 2.0 Hz, 2H),\n compound 3 is inactive. A similar trend was observed for the 1.68 (s, 15H, Cp* CH3), 1.44 (s, 18H, tert-C4H9). 13C{1H} NMR\n medicinal activity of metalated or lipidated antimicrobial (100 MHz, CD2Cl2): \u03b4 = 165.3, 154.1, 151.0, 125.8, 120.3, 97.1 (JRhC =\n peptides, where an C8 chain (octyl group) proved to be 8.6 Hz, Cp* CCH3), 35.7 (CMe3), 30.0 (C CH3), 8.8 (Cp*-CH3).\n optimal[28] \u2013 similar to the nonyl group used here. Interestingly, [Rh(\u03b75-C5Me5)Cl(4,4'-(nonyl)2-2,2'-bpy)]PF6 (2): Yield: 120 mg\n substitution with a metallocene (ferrocene or ruthenocene) (48.4 %). Anal. C38H59ClF6N2PRh (827.23): calcd. C, 55.17; H, 7.19; N,\n proved to have an effect comparable to this octyl 3.39. Found: C, 55.00; H, 7.16; N, 3.28 %. MS (FAB +): m/z = 682.3 [M +\n substitution,[29] so related investigations for bimetallic com- ] complex cation. 1H NMR (400 MHz, CD2Cl2): \u03b4 = 8.62 (d, JHH =\n pounds may be an interesting future direction for the work 5.6 Hz, 2H), 8.01 (d, JHH = 1.6 Hz, 2H), 7.55 (dd, JHH = 5.6 Hz, JHH =\n 1.6 Hz, 2H), 2.68 (m, 8H, Hnon), 1.68 (m, 8H, Hnon), 1.32 (m, 10H, Hnon),\n described herein.\n 1.26 (m, 6H, Hnon), 0.86 (t, JHH = 7.0 Hz, 6H), 1.67 (s, 15H, Cp* CH3).\n 13 1\n C{ H} NMR (100 MHz, CD2Cl2): \u03b4 = 157.6, 154.0, 150.7, 128.4, 123.5,\n 97.0 (JRhC = 7.6 Hz), 35.5, 31.9, 30.2, 29.5, 29.4, 29.3, 29.2, 22.7, 13.9,\n Experimental Section 8.8 (Cp*-CH3).\n\n General: All manipulations were performed under an atmosphere [Rh(\u03b75-C5Me5)Cl(4,4'-(NH2)2-2,2'-bpy)]PF6 (3): Yield: 125 mg (68.9 %).\n of dry nitrogen using conventional Schlenk techniques. Solvents Anal. C20H25ClF6N4PRh (604.77): calcd. C, 39.72; H, 4.17; N, 9.26.\n were dried with standard procedures and stored under nitrogen. Found: C, 39.64; H, 4.17; N, 9.16 %. MS (FAB +): m/z = 459.1 [M + ]\n The corresponding 4,4\u2019-disubstituted-2,2\u2019-bipyridines were pur- complex cation. 1H NMR (400 MHz, CD2Cl2): \u03b4 = 8.06 (d, JHH = 6.4 Hz,\n chased from Aldrich and used as received. The starting complex 2H), 7.22 (d, JHH = 2.8 Hz, 2H), 6.75 (dd, J = 2.8 Hz, J = 6.8 Hz, 2H),\n [{Rh(\u03b75-C5Me5)(\u03bc-Cl)Cl}2] was prepared by the literature method.[30] 5.11 (s, br, 4H, NH2), 1.61 (s, 15H, Cp* CH3). 13C{1H} NMR (acetone-\n NMR spectra were recorded in CD2Cl2 or acetone-d6 using a Jeol d6): \u03b4 = 156.8, 155.1, 151.1, 112.2, 106.7, 95.6 (JRhC = 7.6 Hz), 8.1\n Eclipse 400 instrument operating at 400 MHz (1H) and 100 MHz (13C) (Cp* CH3).\n respectively. The 1H NMR stability tests were recorded in DMSO-d6\n X-ray Crystal Structure Determination: Crystals of 3 suitable for an\n using a Bruker Aviii 300 (300 MHz). Chemical shifts are given in\n X-ray diffraction study were obtained by crystallization from\n ppm, referenced to the solvent signals. Mass spectra were\n dichloromethane/methanol/iso-hexane mixtures at ambient tem-\n measured using a JeolMstation JMS 700 instrument. Elemental\n perature. Crystals were selected by means of a polarization micro-\n analyses (C, H, N) were performed by the Microanalytical Laboratory\n scope, mounted on a MiTeGen MicroLoop, and investigated with a\n of the Department of Chemistry, LMU Munich, using a Heraeus\n Bruker D8 Venture TXS diffractometer using Mo-K\u03b1 radiation (\u03bb =\n Elementar Vario EL instrument.\n 0.71073 \u00c5). The frames were integrated with the Bruker SAINT\n software package.[31] All C-bound hydrogen atoms have been\n calculated in ideal geometry riding on their parent atoms. The N-\n Biological activities\n and O-bound hydrogen atoms have been refined freely. The N H-\n MCF-7, HT-29 and GM5657T cells were grown in Dulbecco\u2019s distances have been restrained to be equal within a standard\n Modified Eagle\u2019s Medium (DMEM), containing 10 % fetal calf serum, deviation of 0.01 \u00c5. The ISOR restraint has been applied for one F\n 1 % penicillin and streptomycin. For harvesting, the cells were atom. The structure has been refined as a 2-component inversion\n detached from the wells with trypsin and EDTA, centrifugated and twin (BASF 0.02). Data were corrected for absorption effects using\n resuspended in the cell culture medium. 96 well plates were the Multi-Scan method (SADABS).[32] The structure was solved by\n prepared with 6000 cells per well for both cell lines and incubated direct methods and refined by full-matrix least-squares calculations\n for 24 h at 37 \u00b0C with 10 % CO2. Afterwards, the cells were treated on F2 using the Bruker SHELXTL Software package.[33] The figures\n with the compounds with a final DMSO concentration of 0.5 %/well. have been drawn at the 25 % ellipsoid probability level using\n For comparison, the growth medium with 0.5 % DMSO was used as ORTEP.[34] The H atoms, the methanol molecules and the hexafluor-\n a negative control. After incubation for 48 h, 50 \u03bcL MTT (2.5 mg/ idophosphate anion respectively, in the Figure 1 have been omitted\n mL) was added and further incubated for 2 h. The medium was for more clarity. Details of the crystal data, data collection, structure\n removed, the formazan dye was dissolved in DMSO, and the solution, and refinement parameters of compound 3 are summar-\n absorption was measured at 550 nm, using 620 nm as a reference ized in Table 2.\n wavelength. All tests were carried out in triplicates in three\n Crystallographic data (excluding structure factors) for the structure\n independent experiments for each cell line.\n in this paper have been deposited with the Cambridge Crystallo-\n Synthesis of compounds 1\u20133: To a suspension of [{Rh(\u03b75-C5Me5)(\u03bc- graphic Data Centre, CCDC, 12 Union Road, Cambridge CB21EZ, UK.\n Cl)Cl}2] (0.15 mmol) in 25 mL of MeOH the corresponding 4,4\u2019- Copies of the data can be obtained free of charge upon quoting\n disubstituted-2,2\u2019-bipyridine (0.3 mmol) was added and the mixture the depository number CCDC-2289088 (3) (Fax: + 44-1223-336-033;\n stirred for 1 h resulting in a clear orange solution. Then KPF6 E-Mail: deposit@ccdc.cam.ac.uk, http://www.ccdc.cam.ac.uk).\n (0.4 mmol) was added and the mixture stirred for additional 30 min.\n At this point the products were dissolved in methanol. To the\n resulting solution diethyl ether (30 mL) was added in each case and\n the mixtures stored at 28 \u00b0C overnight. Thus, the products Acknowledgements\n precipitated as yellows powders which were separated by filtration,\n washed twice with diethyl ether and dried in vacuo affording The authors are grateful to the Department of Chemistry of the\n analytically pure products. Ludwig-Maximilians-Universit\u00e4t Munich for financial support. J.\n O. is supported by a PhD grant from the DFG-funded GRK2341\n (MiCon). Open access funding enabled and organized by Projekt\n\n Z. Anorg. Allg. Chem. 2023, 649, e202300195 (4 of 5) \u00a9 2023 The Authors. Zeitschrift f\u00fcr anorganische und allgemeine Chemie published by Wiley-VCH GmbH\n\f Journal of Inorganic and General Chemistry\n\n\n\n\n 15213749, 2024, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/zaac.202300195 by Lomonosov Moscow State University, Wiley Online Library on [12/05/2026]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License\n RESEARCH ARTICLE\nZeitschrift f\u00fcr anorganische und allgemeine Chemie\n\n\n\n [7] J. M. Hearn, G. M. Hughes, I. Romero-Canel\u00f3n, A. F. Munro, B.\n Table 2. Crystal data and structure refinement details of com-\n Rubio-Ruiz, Z. Liu, N. O. Carragher, P. J. Sadler, Metallomics\n pound 3.\n 2018, 10, 93.\n Compound 3 [8] D.-L. Ma, C. Wu, K.-J. Wu, C.-H. Leung, Molecules 2019, 24, 2739.\n Empirical formula C20H25ClF6N4PRh \u00b7 2 MeOH [9] R. M. Lord, P. C. McGowan, Chem. Lett. 2019, 48, 916.\n M/g mol 1 668.85 [10] W.-Y. Zhang, S. Banerjee, C. Imberti, G. J. Clarkson, Q. Wang, Q.\n Temperature/K 173(2) Zhong, L. S. Young, I. Romero-Canel\u00f3n, M. Zeng, A. Habtemar-\n Crystal system orthorhombic iam, P. J. Sadler, Inorg. Chim. Acta 2020, 503, 119396.\n Space group P212121 [11] S. Banerjee, P. J. Sadler, RSC Chem. Biol. 2021, 2, 12.\n a/\u00c5 12.7951(5) [12] L. Biancalana, H. Kostrhunova, L. K. Batchelor, M. Hadiji, I.\n b/\u00c5 13.6276(5) Degano, G. Pampaloni, S. Zacchini, P. J. Dyson, V. Brabec, F.\n c/\u00c5 15.8246(5) Maschetti, Inorg. Chem. 2021, 60, 9529.\n \u03b1/\u00b0 90 [13] D.-L. Ma, M. Wang, Z. Mao, C. Yang, C.-T. Ng, C.-H. Leung,\n \u00df/\u00b0 90 Dalton Trans. 2016, 45, 2762 and references cited therein.\n \u03b3/\u00b0 90 [14] K. M\u00e1likov\u00e1, L. Masaryk, P. \u0160tarha, Inorganics 2021, 9, 26.\n V/\u00c53 2759.28(17) [15] a) M. Graf, H.-C. B\u00f6ttcher, K. S\u00fcnkel, S. Thavalingam, N. Metzler-\n Z 4 Nolte, R. Czerwieniec, Z. Anorg. Allg. Chem. 2021, 647, 306 and\n 1calcd./g cm3 1.610 references cited therein; b) M. Graf, H.-C. B\u00f6ttcher, N. Metzler-\n \u03bc/mm 1 0.841 Nolte, S. Thavalingam, P. Mayer, Z. Anorg. Allg. Chem. 2022,\n \u03b8 range for data collection/\u00b0 2.977 to 27.480 648, e202200206.\n Reflections observed 6076 [16] M. Graf, J. Ochs, N. Metzler-Nolte, P. Mayer, H.-C. B\u00f6ttcher, Z.\n Reflections in refinement 6324 Anorg. Allg. Chem. 2023, 649, e202200382.\n S 1.079 [17] M. Graf, J. Ochs, N. Metzler-Nolte, H.-C. B\u00f6ttcher, P. Mayer, Z.\n Final R indices [I > 2\u03c3(I)] R1 = 0.0240, wR2 = 0.0631 Anorg. Allg. Chem. 2023, 649, e202300082.\n \u0394\u03c1fin (max/min)/e \u00c5 3 0.623/ 0.556 [18] L. Dadci, H. Elias, U. Frey, A. Hoernig, U. Koelle, A. E. Merbach,\n H. Paulus, J. S. Schneider, Inorg. Chem. 1995, 34, 306.\n [19] W. C. Henke, D. Lionetti, W. N. G. Moore, J. A. Hopkins, V. W.\n Day, J. D. Blakemore, ChemSusChem 2017, 10, 4589.\n DEAL. Open Access funding enabled and organized by Projekt [20] T. K. Todorova, T. N. Huan, X. Wang, H. Agarwala, M. Fontecave,\n Inorg. Chem. 2019, 58, 6893.\n DEAL.\n [21] H. Aneetha, P. S. Zacharias, B. Srinivas, G. H. Lee, Y. Wang,\n Polyhedron 1999, 18, 299.\n [22] M.-T. Youinou, R. Ziessel, J. Organomet. Chem. 1989, 363, 197.\n Conflict of Interest [23] P. Govindaswamy, J. Canivet, B. Therrien, G. S\u00fcss-Fink, P.\n \u0160t\u011bpni\u010dka, J. Ludv\u00edk, J. Organomet. Chem. 2007, 692, 3664.\n The authors declare no conflict of interest. [24] M. Graf, H.-C. B\u00f6ttcher, P. Mayer, Z. Anorg. Allg. Chem. 2021,\n 647, 1316.\n [25] S. Banerjee, J. J. Soldevila-Barreda, J. A. Wolny, C. A. Wootton,\n A. Habtemariam, J. Romero-Canel\u00f3n, F. Chen, G. J. Clarkson, J.\n Data Availability Statement Prokes, L. Song, P. B. O'Connor, V. Sch\u00fcnemann, P. J. Sadler,\n Chem. Sci. 2018, 9, 3177.\n The data that support the findings of this study are available in [26] M. A. Scharwitz, I. Ott, Y. Geldmacher, R. Gust, W. S. Sheldrick, J.\n the supplementary material of this article. Organomet. Chem. 2008, 693, 2299.\n [27] Y. Geldmacher, R. Rubbiani, P. Wefelmeier, A. Prokop, I. Ott,\n W. S. Sheldrick, J. Organomet. Chem. 2011, 696, 1023.\n Keywords: Bidentate N-donor ligands \u00b7 Crystal structure \u00b7 [28] H. B. Albada, P. Prochnow, S. Bobersky, S. Langklotz, P. Schriek,\n Cytotoxic activity \u00b7 Half-sandwich complexes \u00b7 Rhodium J. E. Bandow, N. Metzler-Nolte, ACS Med. Chem. Lett. 2012, 3,\n 980.\n [29] B. Albada, N. Metzler-Nolte, Acc. Chem. Res. 2017, 50, 2510.\n [30] M. A. Matell, J. W. Kampf, M. Sanford, Organometallics 2018, 37,\n [1] K. Peng, Y. Zheng, W. Xia, Z.-W. Mao, Chem. Soc. Rev. 2023, 52, 3240.\n 2790. [31] Bruker (2012). SAINT AXS Inc., Madison, Wisconsin, USA.\n [2] T. S. Prathima, B. Choudhury, M. Ahmad, K. Chanda, M. M. [32] G. M. Sheldrick (1996). SADABS. University of G\u00f6ttingen,\n Balamurali, Coord. Chem. Rev. 2023, 490, 215231. Germany.\n [3] C. N. Morrison, K. E. Prosser, R. W. Stokes, A. Cordes, N. Metzler- [33] G. M. Sheldrick, Acta Crystallogr. 2015, A71, 3.\n Nolte, S. M. Cohen, Chem. Sci. 2020, 11, 1216. [34] L. J. Farrugia, J. Appl. Crystallogr. 2012, 45, 849.\n [4] K. J. Franz, N. Metzler-Nolte, Chem. Rev. 2019, 119, 727.\n [5] J. Li, L. Guo, Z. Tian, M. Tian, S. Zhang, K. Xu, Y. Qian, Z. Liu,\n Dalton Trans. 2017, 46, 15520.\n [6] H. Zhang, L. Guo, Z. Tian, M. Tian, S. Zhang, Z. Xu, P. Gong, X. Manuscript received: September 5, 2023\n Zheng, Z. Liu, Chem. Commun. 2018, 54, 4421. Revised manuscript received: October 28, 2023\n\n\n\n\n Z. Anorg. Allg. Chem. 2023, 649, e202300195 (5 of 5) \u00a9 2023 The Authors. Zeitschrift f\u00fcr anorganische und allgemeine Chemie published by Wiley-VCH GmbH\n\f", "pages_extracted": 5, "text_length": 46859}