Multiple Pathways in the Self-Assembly Process of a Pd4L8

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Cite This: Inorg. Chem. XXXX, XXX, XXX−XXX

Multiple Pathways in the Self-Assembly Process of a Pd4L8 Coordination Tetrahedron Tomoki Tateishi, Tatsuo Kojima, and Shuichi Hiraoka* Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan S Supporting Information *

ABSTRACT: The self-assembly of a Pd418 coordination tetrahedron (Tet) from a ditopic ligand, 1, and palladium(II) ions, [PdPy*4]2+ (Py* = 3-chloropyridine), was investigated by a 1H NMR-based quantitative approach (quantitative analysis of selfassembly process, QASAP), which allows one to monitor the average composition of the intermediates not observed by NMR spectroscopy. The self-assembly of Tet takes place mainly through three pathways and about half of the Tet structures were produced through the reaction of a kinetically produced Pd3L6 double-walled triangle (DWT) and 200-nm-sized large intermediates (IntL). In two of the three pathways, the leaving ligand (Py*), which is not a component of Tet, catalytically assisted the self-assembly. Such a multiplicity of the self-assembly process of Tet suggests that molecular self-assembly takes place on an energy landscape like a protein-folding funnel.

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INTRODUCTION Protein folding takes place through several pathways, entropically favorable but energetically unstable “unfolded states” going down on the surface of an energy funnel to the thermodynamically stable, well-ordered “folded state” (Figure 1a).1−4 Self-assembly is similar to protein folding in that it takes

(amyloid) and artificial systems has recently been advocated.5−17 However, with regard to most of the molecular self-assemblies, because of the difficulty in the observation of transiently produced intermediates during the self-assembly, how molecular self-assembly takes place remains to be explored. The difficulty in the detection and quantification of intermediates by spectroscopy such as NMR spectroscopy arises from the shorter lifetime of the intermediates than the NMR time scale, from the less symmetrical structure of the intermediates, whose chemically inequivalent signals are too weak to be observed, or from the formation of submicrometersized large intermediates. Thus, it is true that monitoring of all of the intermediates is a straightforward way to reveal the molecular self-assembly processes, but the detection and quantification of all of the intermediates is practically impossible. We have recently developed a novel method for the investigation of coordination self-assembly processes, characterizing the average composition of the intermediates not observed by NMR spectroscopy by quantifying all of the observable species (quantitative analysis of self-assembly process, QASAP). 18−24 Coordination self-assembly,25−49 which is constructed with the aid of a coordination bond between the metal ion and organic ligand, is a simpler supramolecular system than biological self-assembly, so understanding such prototypical model systems enables us to abstract common principles in molecular self-assembly. Herein we report the pathway complexity in the coordination selfassembly of a tetrahedron-shaped Pd418 complex (Tet)50 from rigid organic ditopic ligands, 1, and square-planar

Figure 1. Analogy between protein folding and the molecular selfassembly process. (a) Energy funnel of protein folding. Blue, red, and green filled circles indicate one of the unfolded states, the folded state, and a kinetically trapped state, respectively. (b) Energy funnel of molecular self-assembly. Blue, red, and green solid circles indicate one of the disordered states, the self-assembled state, and a kinetically trapped state, respectively.

place from disordered states, where the components of the assembly are apart from each other, to the well-defined assembled state (Figure 1b). Considering the intrinsic similarity between protein folding and the molecular self-assembly process, molecular self-assembly would occur through complicated pathways. Analogy in supramolecular fiber formation through nucleation and growth between biological © XXXX American Chemical Society

Received: December 7, 2017

A

DOI: 10.1021/acs.inorgchem.7b03085 Inorg. Chem. XXXX, XXX, XXX−XXX

Article

Inorganic Chemistry palladium(II) ions, [PdPy*4]2+ (Py* = 3-chloropyridine), shown in eq 1 and Figure 2a 81 + 4[PdPy*4 ]2 + ⇄ [Pd418 ]8 + + 16Py*

This result indicates the analogy between molecular selfassembly and protein folding.

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APPROACH As described above, although monitoring of the time development of all of the intermediates is the simplest way to reveal molecular self-assembly processes, the direct detection and quantification of all of the intermediates are impossible. The concept of QASAP is based on the quantification of all of the observable species,18,19 which in most cases are the substrates and products: 1, [PdPy*4]2+, [Pd418]8+ (Tet), and Py* in eq 1. In the self-assembly of Tet, besides these species, a metastable species (DWT) was detected by 1H NMR (vide infra). Intermediates of the self-assembly in eq 1 are generally expressed by Pda1bPy*c (a−c are positive integers or 0). The (n, k) value for Pda1bPy*c is defined by eqs 2 and 3. 4a − c n= (2) b a k= (3) b

(1)

The n value indicates the average number of palladium(II) ions bound to a single ligand 1, while the k value represents the ratio between palladium(II) and the ligand. If the molecular formula of an intermediate i is expressed as Pdai1biXci, the average molecular formula of all of the intermediates is expressed as Pda1̅ b̅Xc,̅ where a,̅ b̅, and c ̅ are defined as follows: all

a ̅ = ∑i miai ∑all mi i

(4)

all

b ̅ = ∑i mibi ∑all mi i

(5)

all

c ̅ = ∑i mici ∑all mi i

Figure 2. (a) Summary of the self-assembly process of a Pd418 tetrahedron (Tet) from 1 and [PdPy*4]2+ in CD3NO2/CD2Cl2 (v/v = 4/1) at 298 K. Tet is assembled mainly through three pathways in three stages. Arrows colored in blue, red, and green indicate stages I− III, respectively. Optimized structures of (b) Tet and (c) a Pd316 double-walled triangle (DWT) by DFT calculations. Color code; gray, carbon; blue, nitrogen; yellow, palladium. Hydrogen atoms are omitted for clarity.

(6)

where mi is the mole number of species i. The average (n, k) value of all of the intermediates except DWT, (⟨n⟩, ⟨k⟩), is defined as follows:

where Py* is a leaving ligand that coordinates to a palladium(II) center of the metal source in the beginning. The multiple ligand exchanges between Py* and the ditopic ligand 1 lead to the thermodynamically most stable Tet. QASAP revealed that Tet is self-assembled mainly through three pathways: (1) 25% of Tet is quickly produced from small intermediates; (2) the reaction of a metastable Pd316 doublewalled triangle (DWT) with the leaving ligand (Py*) to form a partially broken DWT, which reacts with submicrometer-sized large intermediates (IntL), leads to 45% of Tet through intramolecular ligand exchanges; (3) the catalytic reaction of IntL with the leaving ligand (Py*) leads to 13% of Tet. Even the self-assembly of Tet composed of 12 components, which are much fewer than those in complicated biological molecular self-assemblies such as virus capsids, takes place through multiple pathways, in which the species that is not a component of the final assembly, Py*, intervenes in the self-assembly process and plays a vital role in the efficient formation of Tet.

⟨n⟩ =

4a ̅ − c ̅ b̅

(7)

⟨k⟩ =

a̅ b̅

(8)

The average composition of all of the intermediates (excluding DWT), Pd⟨a⟩1⟨b⟩Py*⟨c⟩, can be determined from the difference between the consumption ratio and the formation ratio of each component in eq 1 and DWT. The ⟨n⟩ and ⟨k⟩ values can also be expressed using ⟨a⟩, ⟨b⟩, and ⟨c⟩ as follows: ⟨n⟩ =

4⟨a⟩ − ⟨c⟩ ⟨b⟩

⟨k⟩ =

⟨a⟩ ⟨b⟩

(9)

(10)

Therefore, n−k analysis allows one to investigate the molecular self-assembly process based on the average composition of all of the intermediates even if none of the intermediates can be detected by spectroscopy. B

DOI: 10.1021/acs.inorgchem.7b03085 Inorg. Chem. XXXX, XXX, XXX−XXX

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Figure 3. Partial 1H NMR spectra (500 MHz, 298 K, aromatic region): (a) 1; (b) PdPy*4(BF4)2; (c) Tet (Pd418); (d) DWT (Pd316) in CD3NO2. Reaction mixture of 1 ([1]0 = 6.0 mM) and PdPy*4(BF4)2 ([Pd]0 = 3.0 mM) in CD3NO2 and CD2Cl2 (4/1, v/v) measured at (e) 5 min, (f) 6 h, (g) 3 days, (h) 2 weeks, and (i) 4 weeks. Blue a−e and a′−e′ indicate the signals for the double-walled and single-walled ligands in Tet, respectively.

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[2.2]paracyclophane in CHCl3 (125 μL), which was used as an internal standard, was added to two NMR tubes (tubes I and II), and the solvent was removed in vacuo. A solution of PdPy*4(BF4)2 (36 mM) and 1,3,5-trimethoxybenzene (15 mM), which was used as a secondary internal standard, in CD3NO2 was prepared (solution A). Solution A (50 μL) and CD3NO2 (450 μL) were added to tube I. The exact concentration of PdPy*4(BF4)2 and 1,3,5-trimethoxybenzene in solution A was determined through a comparison of the signal intensity with that of [2.2]paracyclophane by 1H NMR. A solution of the ditopic ligand 1 (36 mM) in CHCl3 (100 μL) was added to tube II, and the solvent was removed in vacuo. Then CD2Cl2 (120 μL) and CD3NO2 (430 μL) were added to tube II, and the exact amount of 1 in tube II was determined through a comparison of the signal intensity with that of [2.2]paracyclophane by 1H NMR. A total of 0.50 equiv (against the amount of ligand 1 in tube II) of solution A (ca. 50 μL; the exact amount was determined based on the exact concentration of solution A and of 1 in tube II) was added to tube II at 263 K. The selfassembly of Pd418(BF4)8 (Tet) was monitored at 298 K by 1H NMR spectroscopy. Some of the 1H NMR spectra are shown in Figures 3 and S1. The exact ratio of 1 and PdPy*4(BF4)2 was unambiguously determined by a comparison of the integral value of each 1H NMR signal of [2.2]paracyclophane. The amounts of 1, [PdPy*4]2+, [Pd418]8+ (Tet), [Pd316]6+ (DWT), and Py* were quantified by the integral value of each 1H NMR signal against the signal of the internal standard ([2.2]paracyclophane). In order to confirm the reproducibility, the same experiment was carried out three times (runs 1−3) in total. These data, the average values of the existence ratios, and the (⟨n⟩, ⟨k⟩) values are listed in Tables S1−S5. From Pd(CH3CN)4(BF4)2. A 2.4 mM solution of [2.2]paracyclophane in CHCl3 (125 μL), which was used as an internal standard, was added to an NMR tube (tube I), and the solvent was removed in vacuo. A solution of Pd(CH3CN)4(BF4)2 (36 mM) in CD3NO2 was prepared (solution A). Because of the difficulty in the quantification of Pd(CH3CN)4(BF4)2 and CH3CN, the exact concentration of Pd(CH3CN)4(BF4)2 was not determined through a comparison of

EXPERIMENTAL SECTION 1

13

General Information. H and C NMR spectra were recorded using a Bruker AV-500 (500 MHz) spectrometer. All 1H NMR spectra were referenced using residual solvent peaks, CD3NO2 (δ 4.33) and CDCl3 (δ 7.26). A 13C NMR spectrum was referenced using a solvent peak, CD3NO2 (δ 62.81). Electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) spectra were obtained using a Waters Xevo G2-S Tof mass spectrometer. Dynamic light scattering (DLS) measurements were performed using a Malvern Zetasizer Nano ZS instrument equipped with a helium−neon laser operating at 2 mW power and 633 nm wavelength and a computer-controlled correlator at a 173° accumulation angle. Materials. Unless otherwise noted, all solvents and reagents were obtained from commercial suppliers (TCI Co., Ltd., WAKO Pure Chemical Industries Ltd., KANTO Chemical Co., Inc., and SigmaAldrich Co.) and were used as received. CD3NO2 was purchased from Acros Organics and used after dehydration by 4 Å molecular sieves. The ditopic ligand 1 was prepared according to the literature.50 Synthesis. PdPy*4(BF4)2. A solution of Py* (3-chloropyridine; 224 mg, 2.00 mmol) and Pd(CH3CN)4(BF4)2 (111.1 mg, 0.250 mmol) in CH3NO2 (2 mL) was stirred at 70 °C for 2 h under a nitrogen atmosphere. The obtained solution was concentrated in vacuo. The remaining Py* was removed by recrystallization from trichloromethane (CHCl3). The obtained solid was dried in vacuo to afford PdPy*4(BF4)2 as a colorless solid (161.2 mg, 88%). 1H NMR (500 MHz, CD3NO2, 298 K): δ 8.97 (d, JHH = 2.2 Hz, 4H), 8.89 (d, JHH = 1.1 and 5.7 Hz, 4H), 8.06 (ddd, JHH = 1.1, 2.2, and 8.4 Hz, 4H), 7.60 (dd, JHH = 5.7 and 8.4 Hz, 4H). 1H NMR (500 MHz, CDCl3, 298 K): δ 9.38 (d, JHH = 2.1 Hz, 4H), 9.32 (d, JHH = 0.8 and 5.9 Hz, 4H), 7.85 (ddd, JHH = 0.8, 2.1, and 8.3 Hz, 4H), 7.49 (dd, JHH = 5.9 and 8.3 Hz, 4H). 13C{1H} NMR (125 MHz, CD3NO2, 298 K): δ 151.14, 150.97, 142.83, 136.44, 129.53. ESI-TOF-MS. Calcd for C20H16Cl4N4Pd ([PdPy*4]2+): m/z 279.9. Found: m/z 279.9. Monitoring the Self-Assembly Process of a Pd418(BF4)8 Tetrahedron (Tet). From PdPy*4(BF4)2. A 2.4 mM solution of C

DOI: 10.1021/acs.inorgchem.7b03085 Inorg. Chem. XXXX, XXX, XXX−XXX

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Table 1. Time Variation of the Species Detected by ESI-TOF-MS for the Self-Assembly of Pd418 from 1 ([1]0 = 6.0 mM) and PdPy*4(BF4)2 ([Pd]0 = 3.0 mM) in CH3NO2 at 298 Ka 5 min (1, (1, (1, (1, (2, (2, (2, (2, (2, (3, (4,

2, 2, 3, 4, 2, 3, 3, 4, 4, 6, 8,

0) 2) 1) 0) 4) 2) 3) 0) 2) 0) 0)

15 min (1, (1, (1, (1, (2, (2, (2, (2, (2, (3, (4,

2, 2, 3, 4, 2, 3, 3, 4, 4, 6, 8,

0) 2) 1) 0) 4)↓ 2) 3)↓ 0)↓ 2)↓ 0)↑ 0)↑

30 min (1, (1, (1, (1, (2, (2, (2, (2, (2, (3, (4,

2, 2, 3, 4, 2, 3, 3, 4, 4, 6, 8,

0) 2) 1)↓ 0) 4) 2)↓ 3) 0)↓ 2)↓ 0)↑ 0)↑

60 min

90 min

120 min

180 min

(1, 2, 0)

(1, 2, 0)

(1, 2, 0)

(1, 2, 0)

(1, 4, 0)↓ (2, 2, 4) (2, 3, 2)↓

(1, 4, 0)↓ (2, 2, 4) (2, 3, 2)

(1, 4, 0)↓ (2, 2, 4) (2, 3, 2)

(1, 4, 0)↓ (2, 2, 4)↓

(2, 4, 0)↓

(2, 4, 0)

(2, 4, 0)↓

(2, 4, 0)↓

(3, 6, 0)↑ (4, 8, 0)↑

(3, 6, 0)↑ (4, 8, 0)↑

(3, 6, 0)↑ (4, 8, 0)↑

(3, 6, 0)↑ (4, 8, 0)↑

(a, b, c) indicates species Pda1bPy*c. Up and down arrows, ↑ and ↓, indicate an increase and a decrease of the signal intensity compared with the previous measurement, respectively.

a

the signal intensity with that of [2.2]paracyclophane by 1H NMR. A solution of the ditopic ligand 1 (36 mM) in CHCl3 (100 μL) was added to tube I, and the solvent was removed in vacuo. Then CD2Cl2 (120 μL) and CD3NO2 (430 μL) were added to tube I, and the exact amount of 1 in tube I was determined through a comparison of the signal intensity with that of [2.2]paracyclophane by 1H NMR. A total of 0.50 equiv (against the amount of ligand 1 in tube I) of solution A (ca. 50 μL; the exact amount was determined based on the exact concentration of ligand in tube I) was added to tube I at 263 K. The self-assembly of Pd418(BF4)8 (Tet) was monitored at 298 K by 1H NMR spectroscopy. Some of the 1H NMR spectra are shown in Figure S17. The exact ratio of 1 and PdPy*4(BF4)2 was unambiguously determined by the comparison of the integral value of each 1H NMR signal of [2.2]paracyclophane. The amounts of 1, [Pd418]8+ (Tet), and [Pd316]6+ (DWT) were quantified by the integral value of each 1H NMR signal against the signal of the internal standard ([2.2]paracyclophane). The existence ratios of 1, Pd418 Tet, and Pd316 (DWT) are plotted in Figure S18. ESI-TOF-MS Measurement. A 6.7 mM solution of 1 in CD3NO2 (450 μL, 3.0 μmol), a 30 mM solution of PdPy*4(BF4)2 in CD3NO2 (50 μL, 1.5 μmol), and a 6.0 mM solution of NBu4BF4 in CH3NO2 (5 μL, 0.03 μmol), which was used as an internal standard in order to normalize the ion intensities in the MS spectra, were mixed. At each time point, 25 μL of the reaction mixture was taken, diluted with CH3NO2 (500 μL), filtered through a membrane filter (pore size = 0.20 μm), and injected into the mass spectrometer with a 4.0 μL/min flow rate to obtain ESI-TOF-MS spectra (Figures S3 and S4). A list of predominantly observed species is shown in Table 1. Isolation of Pd316(BF4)6 (DWT). A solution of 1 (2.79 mg, 12.0 μmol, 0.50 mM) and PdPy*4(BF4)2 (4.40 mg, 6.00 μmol, 0.25 mM) in CH3NO2 (24 mL) was prepared at 298 K. After 4 h, a solution of Pd(CH3CN)4(BF4)2 (2.93 mg, 6.60 μmol, 6.6 mM) in CH3NO2 (1 mL) was added to the reaction mixture to quench the self-assembly. The reaction mixture was concentrated in vacuo up to 2 mL. A mixture of CHCl3 (4 mL) and diethyl ether (Et2O; 4 mL) was added to the residue. The resulting precipitate was collected by centrifugation, washed twice with a mixed solvent of CHCl3 (4 mL) and Et2O (4 mL), and then dried in vacuo. The precipitate was dissolved in methanol (4 mL), and the resulting suspension was filtered to remove insoluble materials. Et2O (8 mL) was added to the filtrate, which was then centrifuged to obtain DWT as a colorless solid [0.432 μmol as determined by 1H NMR based on the internal standard ([2.2]paracyclophane (0.3 μmol))] in 21.6% yield. 1H NMR (500 MHz, CD3NO2, 298 K): δ 9.96 (d, JHH = 1.9 Hz, 12H), 9.28 (dd, JHH = 0.8 and 5.7 Hz, 12H), 8.32 (ddd, JHH = 0.8, 1.9, and 8.0 Hz, 12H), 7.78 (dd, JHH = 5.7 and 8.0 Hz, 12H), 7.77 (s, 24H). 13C{1H} NMR (125 MHz, CD3NO2, 298 K): δ 151.30, 150.75, 140.77, 140.03, 137.55, 1 2 9 . 9 8 , 1 2 9 . 0 2 . A n a l . C a l c d fo r P d 3 1 6 ( B F 4 ) 6 · 1 5 H 2 O (C96H102B6F24N12O15Pd3): C, 46.05; H, 4.11; N, 6.71. Found: C, 46.35; H, 4.31; N, 6.26. HRMS (ESI-TOF). Calcd for

C96H72BF4N12Pd3 ([Pd316(BF4)]5+): m/z 359.6626. Found: m/z 359.6619. 1H, 13C, and (H,H)-COSY NMR and ESI-TOF-MS spectra of DWT are shown in Figures S5−S8, respectively, and a 1H NMR spectrum and DLS data of the insoluble material that mainly contains IntL are shown in Figures S9 and S10.

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RESULTS AND DISCUSSION The quantitative self-assembly of Tet from 1 and Pd(BF4)2 in dimethyl sulfoxide at 363 K in 5 min was reported.50 In this condition, the uncertainty of the leaving ligand during selfassembly prevents quantification of the metal source and the leaving ligand. In our study, PdPy*4(BF4)2 was used as the metal source because the leaving ligand, Py*, has a slightly weaker coordination ability than the ditopic ligand 1 and has such a strong coordination ability that Py* is not detached from a palladium(II) center in a less coordinative CD3NO2 solvent. When the self-assembly of Tet from 1 ([1]0 = 6.0 mM) and PdPy*4(BF4)2 ([Pd]0 = 3.0 mM) was carried out in a mixed solvent of CD3NO2 and CD2Cl2 (4/1, v/v) at 298 K, all of the substrates (1 and PdPy*4(BF4)2) were completely consumed within 5 min and Tet self-assembled slowly in 4 weeks (Figure 4a). Because two kinds of chemically inequivalent 1 exist in Tet (Figure 2b), two sets of signals of 1 were observed in the 1H NMR spectrum of Tet (Figure 3c). In the 1H NMR spectra of the reaction mixture, one set of signals for 1, besides those for Tet, appeared in the early stage of the self-assembly (signals colored in red in Figure 3e,f) and finally disappeared with an increase in the signals of Tet (Figure 3i). This result indicates that a metastable intermediate with high symmetry was transiently produced during the self-assembly. The effect of the initial concentration of the substrates on the self-assembly of Tet was investigated (Figure 4c,d). The selfassembly at a lower concentration of the substrates ([1]0 = 0.50 mM, [Pd]0 = 0.25 mM) tends to prevent the formation of Tet, whereas the formation of the metastable species was not affected by the concentration of the substrates. Because the formation of Tet was suppressed at a lower concentration, the metastable species was isolated from the reaction mixture at 4 h containing the metastable species, the intermediates not observed by 1H NMR (Int), and Py* by precipitation using several solvents (see the Experimental Section). After isolation of the metastable species, only the 1H NMR signals colored in red in Figure 3d were observed, and all of the signals were assigned by (H,H)-COSY NMR measurement (Figure S7). ESI-TOF-MS of the isolated metastable species showed D

DOI: 10.1021/acs.inorgchem.7b03085 Inorg. Chem. XXXX, XXX, XXX−XXX

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to 540 min), suggesting the formation of Tet and DWT from Int (path 1). After 540 min, DWT started to decrease, while Tet and Int increased and decreased, respectively, which indicates that metastable DWT was converted into Tet (path 2) after 540 min (stage II: from 540 min to 2 weeks). Almost all DWT structures were consumed in 2 weeks, after which the formation of Tet continued by the conversion of Int into Tet (stage III: after 2 weeks; path 3). Int was characterized by n−k analysis. Because all of the substrates (1 and PdPy*4(BF4)2) were consumed within 5 min, the ratio between 1 and palladium(II) in Int, ⟨k⟩, was always 0.5, so Int is expressed as Pda1̅ 2aPy* c.̅ The ⟨n⟩ value was always ̅ smaller than 2 (Figure 4b), which indicates that Int contains Py* (c ̅ > 0) and coordinatively free pyridyl groups of 1. Then the self-assembly of Tet was monitored by DLS measurement (Figure 5). A peak at ca. 200 nm at 10 min (blue line) suggests

Figure 5. Monitoring of the self-assembly of 1 ([1]0 = 6.0 mM) and PdPy*4(BF4)2 ([Pd]0 = 3.0 mM) in CD3NO2 and CD2Cl2 (4/1, v/v) at 298 K by DLS measurement. Blue, red, green, and black lines indicate the reaction mixture measured at 10 min, 3 h, 1 day, and 4 weeks, respectively. The magenta line indicates a solution of pure 1.

Figure 4. (a) Existence ratios of the species in the reaction mixture for the self-assembly of Tet from 1 ([1]0 = 6.0 mM) and PdPy*4(BF4)2 ([Pd]0 = 3.0 mM) in CD3NO2 and CD2Cl2 (4/1, v/v) at 298 K. (b) Change in the ⟨n⟩ value with time. Formation ratios of Tet and DWT for self-assembly from 1 and PdPy*4(BF4)2 in CD3NO2 and CD2Cl2 (4/1, v/v) at 298 K: (c) [1]0 = 6.0 mM and [Pd]0 = 3.0 mM; (d) [1]0 = 0.50 mM and [Pd]0 = 0.25 mM.

the formation of submicrometer-sized large intermediates (IntL),51 which is consistent with the fact that most of the intermediates except for DWT were not observed by 1H NMR spectroscopy. The size of IntL increased at 3 h (red line) and then decreased at 1 day (green line) and in 4 weeks (black line) with the conversion of IntL into Tet (stage III in Figure 4a).52 Monitoring of the very early stage of the self-assembly by ESI-TOF-MS showed several signals assigned to the species that contain fewer components than Tet (Table 1 and Figures S3 and S4). The intensity of these signals decreased with time, accompanied by an increase in the signals of DWT and Tet. The possible structures of the intermediates in Table 1 are shown in Figure 6a. Although the (2, 2, 4) complex has cis and trans isomers (Figure 6b), significant distortion of the ditopic ligands in the trans isomer was confirmed by a molecular modeling study (Figure S21b), so only cis isomers were considered for (2, 2, 4), (2, 3, 3), and (2, 4, 2). All of the species in Figure 6a are partial structures of DWT and Tet. These results suggest that these small intermediates are converted into Tet, DWT, and IntL in stage I. The palladium(II) center of (1, 2, 0), [Pd12]2+, is coordinatively unsaturated. Because no release of Py* from [PdPy*4]2+ took place in CD3NO2, the observation of (1, 2, 0) by ESI-TOF-MS indicates that detachment of two Py* ligands from (1, 2, 2) took place under the ionization condition. In addition, the impossibility of a trans cyclic structure (Figure 6b) suggests that the two palladium(II) ions in (2, 3, 2) and (2, 4, 0) should be connected by only two ditopic ligands in a cis manner. Thus, (2, 3, 2) and (2, 4, 0) would be derived from (2, 3, 3) and (2, 4, 2),

prominent signals assigned to Pd 3 1 6 (m/z 359.8532, [Pd 3 1 6 (BF 4 )] 5+ ; m/z 471.5648, [Pd 3 1 6 (BF 4 ) 2 ] 4+ ; m/z 1030.1394, [Pd316(BF4)4]2+; Figure S8). It is worth noting that, to the best of our knowledge, this is the first report on the isolation of a metastable species transiently produced during coordination self-assemblies. 1 H DOSY NMR spectroscopy of the reaction mixture including the metastable intermediate and Tet showed that the diffusion coefficient (D) of the metastable species is 3.46 × 10−10 m2 s−1, which is larger than that of Tet (D = 3.11 × 10−10 m2 s−1; Figure S2). These results indicate that the metastable species is a Pd316 double-walled triangle (DWT). Significant distortion of the ditopic ligands or the coordination geometry of the palladium(II) centers was not found in the optimized structure of DWT by a density functional theory (DFT) calculation (Figure 2c), suggesting that the formation of DWT, which is composed of fewer components than Tet, is reasonable during the self-assembly. Because the metastable species observed by 1H NMR was revealed to be DWT, the existence ratio of the intermediates not observed by 1H NMR (Int) was quantified (orange line in Figure 4a). DWT (5%) and Int (95%) were quickly produced within 5 min, while Tet began to be produced at 20 min; the yield of Tet was 8%. Tet (25%) and DWT (23%) were formed with a decrease in Int (48%) from 5 to 540 min (stage I: from 0 E

DOI: 10.1021/acs.inorgchem.7b03085 Inorg. Chem. XXXX, XXX, XXX−XXX

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which is understandable because the ligand exchange on palladium(II) centers takes place through an associative mechanism in which an incoming ligand coordinates to a palladium(II) center to form square-pyramidal intermediates and a trigonal-bipyramidal transition state.53−55 Thus, in stage II, the coordination of free pyridyl groups of 1 in IntL and/or Py* to the palladium(II) centers in DWT should trigger the conversion of DWT into Tet. In the presence of Py*, DWT was converted into Tet in only 2 days (Figures 7b, 8a, and S12), which is much faster than the

Figure 6. (a) Possible structures of the intermediates observed by ESITOF-MS at the beginning of the self-assembly (Table 1). (b) cis and trans isomers of [Pd212Py*4]4+.

respectively, through the removal of Py* during the ionization. The observation of such coordinatively unsaturated species suggests the formation of some other species with more Py* ligands than the intermediates listed in Table 1 at the early stage of the self-assembly. After the isolation, DWT was stable without any spectral changes in CD3NO2 at 298 K for 2 weeks (Figures 7a and S11),

Figure 8. (a) Existence ratios of the species for the reaction of DWT ([DWT]0 = 0.38 mM) and Py* ([Py*]0 = 14 mM) in CD3NO2 at 298 K (Figure 7b). (b) Change in the ⟨n⟩ value with time.

conversion of DWT under the self-assembly condition (stage II in Figure 4a). This result indicates that Tet can be produced from DWT and Py* through the coordination of Py* to the palladium(II) centers of DWT but that Tet was not produced through such a pathway under the condition of the selfassembly of Tet from 1 and [PdPy*4]2+. In order to obtain the information about the intermediates for the conversion of DWT into Tet in the presence of Py*, n− k analysis was carried out (Figure 8b). The (⟨n⟩, ⟨k⟩) value stayed around (1.88, 0.5), which indicates that the average composition of the intermediates is expressed as Pd316Py*0.72. Thus, the following reaction mechanism is envisaged. DWT (Pd316 ) + Py* → Pd316 Py*1

(11)

Pd316 Py*1 + DWT (Pd316 ) → Pd6112 Py*1

(12)

Pd6112 Py*1 → Tet (Pd418 ) + Pd 214 Py*1

(13)

Py* coordinates to one of the palladium(II) centers of DWT at first to form a partially broken DWT, Pd316Py*1 (eq 11), and the free pyridyl group of 1 in Pd316Py*1 coordinates to one of the palladium(II) centers of another DWT to form a dimer, Pd6112Py*1 (eq 12). Then the intramolecular ligand exchanges in the dimer afford Tet (eq 13). When one of the products in eq 13, Pd214Py*1, reacts with DWT (Pd316), the resulting Pd5110Py*1 would also be converted into Tet through intramolecular ligand exchanges. In a similar way, Pd418Py*1 should be produced as the intermediate. The coexistence of

Figure 7. Reactions of the component(s) existing in the reaction mixture during the self-assembly of Tet. (a) Conversion of the isolated DWT ([DWT]0 = 0.31 mM) into Tet. (b) Reaction of DWT ([DWT]0 = 0.38 mM) and Py* ([Py*]0 = 14 mM) to lead to Tet. (c) Reaction of DWT and IntL. F

DOI: 10.1021/acs.inorgchem.7b03085 Inorg. Chem. XXXX, XXX, XXX−XXX

Article

Inorganic Chemistry

negative (eq 16), which is consistent with a decrease in the ⟨n⟩ value after 2 weeks (stage III in Figure 4b).

Pdx12xPy*1 (x = 3−6) as the intermediates is consistent with the (⟨n⟩, ⟨k⟩) value of (1.88, 0.5). Next, the possibility of conversion from DWT and IntL into Tet was examined (Figure 7c). Et2O was added to the reaction mixture of the self-assembly of Tet from 1 and [PdPy*4]2+ at 5 h to selectively solubilize Py* in Et2O, and a mixture of DWT, Tet, and IntL was obtained as a precipitate. 1H NMR monitoring of the mixture in CD3NO2 at 298 K showed no further formation of Tet (Figures S13 and S14), indicating that Tet was not produced from DWT and IntL even though IntL has free pyridyl groups of 1. This result implies that coordination of the free pyridyl groups of 1 in IntL is prevented probably because these free pyridyl groups are sterically covered. To check the reactivity of the free pyridyl groups of 1 in IntL, PdPy*4(BF4)2 was added in a mixture of DWT, Tet, and IntL, but no release of Py* was observed (Figures S15 and S16), indicating that the coordination ability of the free pyridyl groups of 1 in IntL is not strong enough to bring about the formation of Tet. These results indicate that Py* is essential for the conversion of DWT into Tet. Indeed, when the self-assembly of Tet was carried out from 1 and Pd(CH3CN)4(BF4)2 in CD3NO2 and CD2Cl2 (4/1, v/v) at 298 K, DWT was produced in 17% yield, but no conversion of DWT into Tet took place for 4 weeks under this condition (Figures S17 and S18).56 On the other hand, the addition of Py* in the reaction mixture at 12 h brought about the conversion of DWT and IntL into Tet in 2 weeks (Figures S19 and S20). This result indicates that, although Py* is not a component of Tet, the conversion of metastable DWT into Tet is catalytically assisted by Py*. When all of the results are gathered, the conversion of DWT into Tet under the self-assembly condition (stage II) should take place through the following pathway: DWT (Pd316 ) + Py* → Pd316 Py*1

Δn =

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(11)

(14)

The coordination of Py* to one of the palladium(II) centers of DWT leads to Pd316Py*1 (eq 11), of which the free pyridyl group of 1 next reacts with IntL, followed by intramolecular ligand exchanges to produce Tet and other intermediates not observed by 1H NMR (eq 14). Because 45% of Tet was produced in stage II, the reaction of DWT and IntL in the presence of Py* is the dominant pathway in the self-assembly of Tet. After complete consumption of DWT (2 weeks), IntL slowly converted into Tet (stage III). Considering that the coordination ability of the free pyridyl groups of 1 in IntL is too weak to coordinate to even the more reactive palladium(II) center of [PdPy*4]2+, the conversion of IntL into Tet should be triggered by the coordination of Py* to the palladium(II) centers in IntL, followed by intramolecular ligand exchanges. In addition, the constant value of the existence ratio of Py* indicates that Py* is involved in the conversion of IntL into Tet as the catalyst (eq 15).

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(a ̅ ≫ 4)

(16)

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.inorgchem.7b03085. Further figures and tables and NMR and MS data (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Shuichi Hiraoka: 0000-0002-9262-4747 Notes

The authors declare no competing financial interest.

■

IntL (Pd a ̅ 12a ̅ Py* c ̅ ) + d Py* → Pd418 + Pd a ̅ − 412a ̅ − 8 Py* c ̅ + d Py*

(a ̅ ≫ 4, c ̅ > 0)

CONCLUSIONS In conclusion, the self-assembly process of a tetrahedronshaped Pd418 complex (Tet) was revealed by QASAP. Tet is assembled mainly through three pathways in three stages. In stage I (2 weeks), the remaining IntL is slowly converted to Tet, initiated by the coordination of Py* to the palladium(II) center(s) of IntL (path 3). Such multiple pathways in the self-assembly process of Tet suggest that, like protein folding, molecular self-assembly takes place going down on an energy landscape of a funnel starting from a mixture of components to the thermodynamically most stable state (Figure 1b). It was also found that Py*, which is not a component of the final assembly, plays an important role in the self-assembly of Tet (paths 2 and 3). In the absence of Py*, metastable DWT and IntL could not be transformed into Tet at 298 K. Once the metastable DWT is isolated, such a kinetically trapped species is stable under ambient condition but is converted into Tet in the presence of a molecule possessing coordination ability. If a kinetically trapped species is mixed with some other components in a certain stoichiometry under mild condition, another self-assembly would take place on a new energy landscape, leading to other self-assembled species that cannot be accessed under thermodynamic control, which must be a novel approach in molecular self-assembly.

Pd316 Py*1 + IntL (Pda12a Py*c )→ Tet (Pd418 ) + Pd a ̅ − 112a ̅ − 2 Py* c ̅ + 1 − d + d Py*

−8 c ̅