Article Cite This: Inorg. Chem. XXXX, XXX, XXX−XXX
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Tetravalent Metal Ion Guests in Polyoxopalladate Chemistry: Synthesis and Anticancer Activity of [MO8Pd12(PO4)8]12− (M = SnIV, PbIV) Peng Yang,†,△ Tian Ma,† Zhongling Lang,‡ Sonja Misirlic-Dencic,§ Andjelka M. Isakovic,§ Attila Bényei,# Mirjana B. Č olović,∥ Ivanka Markovic,§ Danijela Z. Krstić,⊥ Josep M. Poblet,‡ Zhengguo Lin,*,†,∇ and Ulrich Kortz*,† Downloaded via NOTTINGHAM TRENT UNIV on August 14, 2019 at 20:34:56 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.
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Department of Life Sciences and Chemistry, Jacobs University, Campus Ring 1, 28759 Bremen, Germany Departament de Química Física i Inorgànica, Universitat Rovira i Virgili, c/Marcel·lí Domingo 1, 43007 Tarragona, Spain § Institute of Medical and Clinical Biochemistry, Faculty of Medicine, ∥Department of Physical Chemistry, “Vinča” Institute of Nuclear Sciences, and ⊥Institute of Medical Chemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia # University of Debrecen, Department of Physical Chemistry, Egyetem tér 1, 4032 Debrecen, Hungary ∇ Key Laboratory of Cluster Science, Ministry of Education of China, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, P.R. China ‡
S Supporting Information *
ABSTRACT: The first two examples of polyoxopalladates(II) (POPs) containing tetravalent metal ion guests, [MO8Pd12(PO4)8]12− (M = SnIV, PbIV), have been prepared and structurally characterized in the solid state, solution, and gas phase. The interactions of the metal ion guests and the palladium-oxo shell were studied by theoretical calculations. The POPs were shown to possess anticancer activity by causing oxidative stress inducing caspase activation and consecutive apoptosis of leukemic cells.
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candidates for encapsulation inside the Pd12 host.5b To enrich the host−guest chemistry of POPs and to try and unravel the associated formation mechanism, the incorporation of tetravalent metal ions into POPs is promising from a structural perspective, but perhaps also relevant en route to biofunctional materials. Albeit supported by computational studies, it proved to be experimentally rather challenging to incorporate tetravalent metal ions into POP shells. Here we report on two POP nanocubes incorporating the tetravalent metal ions SnIV and PbIV.
INTRODUCTION At the cutting edge of polyoxometalate (POM) chemistry, polyoxo-noble-metalates (PONMs) represent an emerging class of molecular noble metal-oxo nanoclusters, usually prepared via self-condensation of square-planar (PdIIO4 or AuIIIO4) building units in aqueous media, and terminated by external heterogroups (e.g., AsO43−, PO43−, and SeO32−) capping the discrete assemblies.1,2 Polyoxopalladates(II) (POPs), as the most significant subset of PONMs, have witnessed an impressive development ever since the pioneering discovery in 2008 of the first POP, [Pd13O8(AsO4)8H6]8− (Pd13),1b primarily engineered with a view to their salient physiochemical properties as well as broad applications, especially in noble metal-based catalysis.3−7 Among the multitude of POP structures, the guest metal-encapsulated, cuboid-shaped [MO8Pd12L8]n− 3b−f,5a,b and the star-shaped [MO10Pd15L10]n− 4,5a (M = guest metal ion, L = heterogroup), constitute the dominant motifs. It has been well-established that the guest M covers as many as 30 different metal ions with charges ranging from +1 to +3 and ionic radii across the periodic table. Particularly, in previous work we had predicted that tetravalent cations (e.g., SnIV and PbIV) are also potential © XXXX American Chemical Society
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EXPERIMENTAL SECTION
Materials and Physical Measurements. All reagents were purchased from commercial sources and used without further purification. The 31P NMR spectra of the obtained compounds were recorded on a 400 MHz JEOL ECX instrument at room temperature, using 5 mm tubes for 31P with resonance frequency 162.14 MHz. The chemical shift is reported with respect to the reference 85% H3PO4. The FT-IR spectra were recorded on KBr disk using a Nicolet-Avatar 370 spectrometer between 400 and 4000 cm−1. Received: April 17, 2019
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DOI: 10.1021/acs.inorgchem.9b01129 Inorg. Chem. XXXX, XXX, XXX−XXX
Inorganic Chemistry
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Elemental analyses were performed by Crealins, Villeurbanne, France. Thermogravimetric analyses (TGA) were carried out on a TA Instruments SDT Q600 thermobalance with a 100 mL min−1 flow of nitrogen; the temperature was ramped from 20 to 800 °C at a rate of 5 °C min−1. The ESI-MS spectra measurements were made in the negative ion mode on an Agilent 6520 Q-TOF LC/MS mass spectrometer coupled to an Agilent 1200 LC system, and all the MS data were processed by the MassHunter Workstation software. Sample solutions were ca. 10−5 M in water and were transferred to the electrospray source by direct injection. Synthesis of Na12[SnO8Pd12(PO4)8]·43H2O (Na-SnPd12). Pd(CH3COO)2 (0.023 g, 0.100 mmol) and SnCl4·5H2O (0.009 g, 0.025 mmol) were dissolved in 0.5 M NaH2PO4 solution (2 mL, 1 mmol, pH 6.9). The solution was heated to 80 °C under stirring, and during the first 30 min, the pH of the solution was adjusted to about 8.0 by addition of 1 M NaOH. The resulting solution was heated at 80 °C for another 60 min, then the solution was allowed to cool to room temperature, filtered, and the filtrate left for crystallization at room temperature in an open vial. Dark red, block-shaped crystals were obtained after 2 weeks, which were collected by filtration and airdried. Yield: 0.011 g (38% based on Pd). Elemental analysis (%): Calcd: Na 8.27, Sn 3.56, Pd 38.30, P 7.43. Found: Na 8.74, Sn 3.28, Pd 37.72, P 7.40. IR (2% KBr pellet, ν/cm−1): 1635 (m), 1417 (w), 1263 (w), 1130 (s), 1070 (m), 954 (s), 920 (w), 867 (w), 821 (w), 623 (s), 540 (w), 517 (w). Synthesis of Na12[PbO8Pd12(PO4)8]·38H2O (Na-PbPd12). Pd(CH3COO)2 (0.023 g, 0.100 mmol) and PbO2 (0.005 g, 0.02 mmol) were dissolved in 0.5 M NaH2PO4 solution (2 mL, 1 mmol, pH 6.9). The solution was heated to 80 °C under stirring for 90 min, then the solution was allowed to cool to room temperature, filtered, and the filtrate left for crystallization at room temperature in an open vial. Dark red, block-shaped crystals were obtained after 2 weeks, which were collected by filtration and air-dried. Yield: 0.007 g (24% based on Pd). Elemental analysis (%): Calcd: Na 8.28, Pb 6.22, Pd 38.32, P 7.44. Found: Na 8.27, Pb 6.21, Pd 38.52, P 7.44. IR (2% KBr pellet, ν/cm−1): 1630 (m), 1130 (s), 947 (s), 914 (s), 621 (s), 553 (w), 455 (w). X-ray Crystallography. Crystal data for Na-SnPd12 were collected at 100 K on a Bruker Kappa X8 APEX CCD single-crystal diffractometer equipped with a sealed Mo tube and a graphite monochromator (λ = 0.71073 Å). Crystal data for Na-PbPd12 were collected at 150 K on a BrukerD8 Venture diffractometer equipped with INCOATEC IμS 3.0 dual sealed tube microsource using Mo Kα radiation (λ = 0.71073 Å) and INCOATEC multilayer mirror monochromator. The detector was PHOTON II Charge-Integrating Pixel Array detector. The crystals were mounted in a Hampton cryoloop with light oil to prevent loss of crystal waters. The SHELX software package (Bruker)8 was used to solve and refine the structures. An empirical absorption correction was applied using the SADABS program.9 The structures were solved by direct methods and refined by the full-matrix least-squares method (Σw(|F0|2 − |Fc|2)2) with anisotropic thermal parameters for all heavy atoms included in the model. It was impossible to locate all sodium counter cations by XRD, due to crystallographic disorder, and it was also impossible to locate hydrogens of crystal waters, which are common issues in polyoxometalate crystallography. The exact number of counter cations and crystal waters in the formula units were derived from elemental analysis, and these formulas were used throughout the manuscript and the cif file for overall consistency. The crystal data and structure refinement for the two compounds are summarized in Table S1. Further details on the crystal structure investigation may be obtained from the Fachinformationszentrum Karlsruhe, 76344 Eggenstein-Leopoldshafen, Germany (fax: (+49) 7247−808−666; e-mail: crysdata@fiz-karlsruhe.de), on quoting the depository numbers CCDC 1906258 (Na-SnPd12) and CCDC 1906257 (Na-PbPd12).
Article
RESULTS AND DISCUSSION Synthesis and Structure. The two tin(IV)- and lead(IV)containing POPs [MIVO8Pd12(PO4)8]12− (MPd12, MIV = SnIV (SnPd12) and PbIV (PbPd12)) were synthesized by direct reaction of the composing elements in aqueous phosphate solution at pH 6.9 (see Experimental Section for details). The two POPs were isolated as hydrated sodium salts, Na 1 2 [Sn I V O 8 Pd 1 2 (PO 4 ) 8 ]·43H 2 O (Na-SnPd 1 2 ) and Na12[PbIVO8Pd12(PO4)8]·38H2O (Na-PbPd12). The structures of SnPd12 and PbPd12 are reminiscent of that of the parent Pd13,1b with the central atom and heterogroups being substituted by SnIV/PbIV and PO43−, respectively (Figure 1a).
Figure 1. (a) Ball-and-stick representation of MPd12 (M = SnIV, PbIV). Color code: Sn and Pb, turquoise; Pd, blue; P, fuchsia; O, red. (b−e) Representation of the onion-type multishell structure of MPd12.
The octa-coordinated M ion is centered within a {MO8} cuboid moiety (Figure 1b, Sn−O 2.224(3) Å and Pb−O 2.292(8) Å), in which the eight μ4-oxo ligands, spanning a cuboid ligand field, bridge the central guest and three PdII ions situated on a trigonal face (Figure 1c). The 12 PdII addenda complete the expected square-planar geometry by coordination with 24 “outer” oxo groups, yielding a truncated cuboid shell (Figure 1d). The resulting {MO8Pd12O24} fragment is further capped by eight positively charged (PVO)3+ groups, leading to an onion-like multishell assembly (Figure 1e). Bond valence sum (BVS)10 calculations suggest that the oxidation state of the Sn and Pb atom is +4, and no oxygens of both polyanions B
DOI: 10.1021/acs.inorgchem.9b01129 Inorg. Chem. XXXX, XXX, XXX−XXX
Article
Inorganic Chemistry are protonated (Table S2). The overall charge of each POP is balanced in the solid state by sodium counter cations, as shown by XRD and elemental analysis. It is worth mentioning that PbPd12 accommodates the heaviest metal ion guest so far in POP chemistry (Pb, relative atomic mass 207.2(1)). The solution stability of the two as-synthesized POPs was verified by 31P NMR spectroscopy after redissolution of the product salts in H2O/D2O. Both 31P NMR spectra exhibit the expected singlet at 13.2 and 12.7 ppm for SnPd12 and PbPd12, respectively, as well as a pair of satellites originating from 31 117 P{ Sn/119Sn} (117Sn: I = 1/2, 7.7%; 119Sn: I = 1/2, 8.6%) and 31P{207Pb} (207Pb: I = 1/2, 22.1%) coupling with coupling constants of 34.0 Hz for the former and 108.4 Hz for the latter, indicating that the discrete POP structures are maintained in aqueous media (Figure 2).
Figure 3. Negative-ion mass spectra of (a) Na-SnPd12 and (b) NaPbPd12.
{Na 7 H 2 SnPd 12 (H 2 O)} 3− , {Na 6 H 3 SnPd 12 (H 2 O)} 3− , and {Na8HSnPd12(H2O)}3−, respectively. In the case of NaPbPd12, a series of distribution peaks can be clearly assigned to species related to PbPd12 (Figure 3b). The main peak located at m/z = 850.81 corresponds to {Na7H2PbPd12(H2O)}3−. The small envelopes positioned at m/z = 572.85 (Figure 3a) and m/z = 594.87 (Figure 3b) can be assigned to the −4 charged protonated ions {H8SnPd12}4− and {H8PbPd12}4−, respectively. Additional MS details and assignments for both polyanions are summarized in Table S3 and Figures S1−S3. Theoretical Study. A large number of control experiments have shown that within the rich reservoir of tetrahedral heterogroups in POP synthesis only the phosphate-capped MIV-containing POPs could be successfully prepared. Previously, in a systematic theoretical analysis, we disclosed that the main factors controlling the incorporation of metal ion guests in POP nanocube (Pd12) shells are related to (i) dehydration of the cation, (ii) deformation of the Pd12 host shell, and (iii) binding between the cation and the Pd12 host. We had also predicted that tetravalent cations were potential candidates to be encapsulated inside the Pd12 host, due to their very exothermic complexation energy.5b Herein, in an effort to try and rationalize the preferable trend for the phosphate capping group observed in the experimental work, DFT calculations at the B3LYP level of theory were carried out to reveal the role of the heterogroups in the formation of tetravalent guest-incorporated POP species.11 The encapsulation of SnIV ions by Pd12L8, with L = PO43−, AsO43−, PhAsO32−, and SeO32−, were compared. Generally, the calculated complexation ability (Ecom) for SnIV becomes more favorable (exothermic) as the formal negative charge of the heterogroup increases from 2− to 3−; see Table 1. This result is in line with the increase of nucleophilicity observed inside the cavity when comparing different capping groups. Hence, the molecular electrostatic potential (MEP, Figure S4) analysis for Pd12L8 cages shows a negative electrostatic potential in the center of the cavity with a distribution order of: PO43− > AsO43− > SeO32− > PhAsO32−. It is very instructive to compare PO43− and SeO32−, whose cavities are essentially identical in size (dO−O). Nevertheless, Ecom for PO43− is more favored than that for SeO32− by 30.6 kcal mol−1, due to the higher negative
Figure 2. 31P NMR spectra of (a) Na-SnPd12 and (b) Na-PbPd12 recorded in H2O/D2O at room temperature.
Moreover, mass spectrometry (ESI-MS) was employed to provide additional structural information and polyanionic stability in the gas phase. The spectrum of Na-SnPd12 shows that all major envelopes are related to the intact polyanion SnPd12 (Figure 3a). The main peak centered at m/z = 821.45 and its neighboring envelopes situated at m/z = 814.12 and 828.77 correspond to −3 charged protonated and sodium form of SnPd 12 , for which the abbreviated formulas are C
DOI: 10.1021/acs.inorgchem.9b01129 Inorg. Chem. XXXX, XXX, XXX−XXX
Article
Inorganic Chemistry Table 1. Complexation Energy Ecom (kcal·mol−1) of SnIV Encapsulated in Pd12L8 (L = PO43−, AsO43−, SeO32−, and PhAsO32−) Host Shell and Its Composing terms ΔEdehyd, ΔEbind, and ΔEdefa Ln−
Ecom
ΔEdeform
ΔEbind
ΔEdehyd
PO43− AsO43− SeO32− PhAsO32− PO43− (Pb)
−256.8 −251.8 −226.2 −223.7 −243.4
20.1 24.0 18.2 20.6 11.9
−2104.7 −2103.6 −2072.2 −2072.1 −1953.2
1827.8 1827.8 1827.8 1827.8 1697.8
Table 2. In Vitro Cytotoxicity of SnPd12 and PbPd12 against Human Acute Promyelocytic Cell Line HL-60 Determined by Acid Phosphatase Assaya IC50 (μM) time
SnPd12
PbPd12
cis-platinum
24 h 48 h 72 h
37.1 ± 4.4 34.3 ± 0.4 32.6 ± 8.1
34.7 ± 9.2 19.3 ± 3.6* 15.4 ± 1.6*
17.4 ± 3.3 5.7 ± 2.2 n.a.
a The values represent means ± SD from three independent experiments. n.a. = not assessed. *, p < 0.05 compared with SnPd12.
a
The dehydration energy (Edehyd) of the cation guest M and the electrostatic interaction (Ebind) between M and the Pd12 nanocage exhibit large values, and Ebind is larger than the sum Edehyd + Edeform. Consequently, the Ecom term is always negative and hence exothermic.
charge density in the former, thus resulting in stronger host− guest interactions (ΔEbind), as shown in Table 1. However, there is only a rather small difference (
