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Syntheses, structures, and properties of two dinuclear palladium (II) complexes of a single macrocyclic hexaaza ligand with two hydroxyethyl pendants
Inorganic Chemistry Communications 8 (2005) 862–865 www.elsevier.com/locate/inoche
Syntheses, structures, and properties of two dinuclear palladium (II) complexes of a single macrocyclic hexaaza ligand with two hydroxyethyl pendants Gaosheng Yang a
a,b
, Huiwei Tang a, Yizhi Li a, Jing Hong a, Zijian Guo a, Longgen Zhu
a,*
State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, Nanjing University, Nanjing 210093, China b College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241000, China Received 7 June 2005; accepted 21 June 2005 Available online 8 August 2005
Abstract Two dinuclear palladium (II) complexes, trans-[Pd2LCl2](ClO4)2 Æ 2H2O and cis-[Pd2LCl2]Cl2 Æ 2H2O, of a single macrocyclic ligand with two hydroxyethyl pendants, L (L = 3,6,9,16,19,22-hexaaza-6,19-bis(2-hydroxyethyl)tricyclo[22,2,2,211,14]triaconta1,11,13,24,27,29-hexaene), have been synthesized as ‘‘inorganic proteases’’ and analyzed by X-ray diffraction method. The two complexes-mediated hydrolytic cleavage of amide bond in acetyl methionyl alanine has been monitored by 1H NMR, showing a moderate hydrolytic rate at 50 C and pH ca. 1.0. The pendent hydroxyl group is responsible for the hydrolytic reaction. 2005 Elsevier B.V. All rights reserved. Keywords: Dinuclear palladium (II) complex; Macrocyclic hexaaza; ESI–MS; Inorganic proteases
Over the past decade, the site-specific non-enzymatic hydrolysis of amide bond in peptides and proteins has been attracting much attention [1–8]. To the best of our knowledge, the reported Pd(II) [3–7] and Pt(II) [6– 8] complexes, in nature, are mononuclear complexes, and at least an aqua ligand is required for activation of amide bond by delivery mechanism or for replacement of it by carbonyl oxygen via extra water attack mechanism [3a,5b–7,9]. However, in some serinecontaining peptidases, the hydroxyl group of serine plays key role in catalytic hydrolysis of amide bond in proteins [10]. To mimic the function, a single macrocyclic ligand with two hydroxyethyl pendants, L (L = 3,6, 9,16,19,22-hexaaza-6,19-bis(2-hydroxyethyl)tricyclo[22, 2,2,211,14]triaconta-1,11,13,24,27,29-hexaene) was used as ligand to synthesize two new dinuclear palladium *
Corresponding author. Tel.: +86 25 8359 7066; fax: +86 25 8331 4502. E-mail address: [email protected] (L. Zhu). 1387-7003/$ - see front matter 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.inoche.2005.06.022
(II) complexes for investigating their ability to hydrolysis of methionine-containing dipeptide. The ligand L was synthesized based on a published procedure [11]. Complex 1, trans-[Pd2LCl2](ClO4)2 Æ 2H2O, was obtained by reaction of L with two equivalents of K2PdCl4 in water at 60 C and crystallized as yellow block crystals from the aqueous solution after adding NaClO4 saturated solution and stored in a refrigerator [12]. However, reaction of L with two equivalents of trans-Pd(PhCN)2Cl2 [13] in methanol solution under reflux conditions generated complex 2, cis-[Pd2LCl2] Cl2 Æ 2H2O, which was recrystallized as yellow block crystals from a concentrated aqueous solution stored in a refrigerator [14]. ESI mass spectrum [15] of complexes 1 and 2 (Fig. S1) shows that the cations of two complexes have the same composition. The peak at m/z 391.0 with doubly positive charges was observed, corresponding to the species of [Pd2LCl2]2+. This species was confirmed by good agreement between the observed (Fig. S1(A)) and
G. Yang et al. / Inorganic Chemistry Communications 8 (2005) 862–865
calculated isotopic distribution pattern (Fig. S1(B)). Xray analysis [16] indicates that the macrocyclic ligands in the two complexes possess two different conformations, which can only be accomplished by stereochemical inversion at one (or more) of the nitrogen atoms (at least, one of the two tertiary nitrogen atoms) of the free macrocyclic ligand in the formation of the complexes [17]. The dinuclear Pd(II) complex 1 crystallizes in a monoclinic space group P21/c. The crystal structure of 1 consists of cationic unit of trans-[Pd2LCl2]2+, two non-coordinated perchlorate ions and two water molecules. A perspective view of the cationic complex is shown in Fig. 1. In the dinuclear Pd(II) complex, each Pd(II) is coordinated by diethylenetriamine moiety, with bond distances of Pd–N, from 2.031(4) to ˚ which are typical for this type of coordina2.076(4) A tion [18], and each Pd(II) ion adopts a distorted square configurations in the N3Cl environment. The distance ˚ . The two between the two Pd(II) ions is 7.088(2) A non-coordinated hydroxyethyl arms of the macrocycle ligand are located at opposite sides of the plane defined by the nitrogen atoms and the phenyl groups of the macrocyclic ligand. The cationic complex forms a chair-like (anti) conformation. Unlike 1, the dinuclear Pd(II) complex 2 crystallizes in a triclinic P 1. The asymmetric unit consists of a cis[Pd2LCl2]2+ cation, two counterpart chloride anions and two disordered water molecules occupying five positions in occupancy of 0.36(1), 0.40(1), 0.45(1), 0.47(1), 0.32(1), respectively. Fig. 2 shows the ORTEP drawing of the cationic complex. In the cationic complex, each Pd(II) ion has a distorted square configuration in the N3Cl environment. The two palladium ions
Fig. 1. ORTEP drawing of the cationic complex 1 with 30% thermal ellipsoids (the hydrogen atoms are omitted for clarity). Selected bond ˚ ): Pd–N1 2.031(4), Pd–N2 2.072(6), Pd–N3 2.076(4), Pd–Cl1 lengths (A 2.297(2); selected bond angles (): Cl1–Pd–N1 175.3(1), Cl1–Pd–N2 94.2(2), Cl1–Pd–N3 92.3(2), N1–Pd–N2 87.2(2), N1–Pd–N3 85.5(2), N2–Pd–N3 168.5(2).
863
Fig. 2. ORTEP drawing of the cationic complex 2 with 30% thermal ellipsoids (the hydrogen atoms are omitted for clarity). Selected bond ˚ ): Pd1–N1 2.030(4), Pd1–N2 2.024(3), Pd1–N3 2.051(5), lengths (A Pd1–Cl1 2.307(2), Pd2–N4 2.039(5), Pd2–N5 2.015(4), Pd2–N6 2.033(4), Pd2–Cl2 2.308(2); selected bond angles (): Cl1–Pd1–N1 94.6(1), Cl1–Pd1–N2 176.5(1), Cl1–Pd1–N3 94.5(1), N1–Pd1–N2 85.8(2), N1–Pd1–N3 165.1(2), N2–Pd1–N3 84.4(2), Cl2–Pd2–N4 95.8(1), Cl2–Pd2–N5 178.2(1), Cl2–Pd2–N6 94.0(1), N4–Pd2–N5 84.4(2), N4–Pd2–N6 164.8(2), N5–Pd2–N6 85.5(2).
˚ apart from each other. The two nonare 6.813(2) A coordinated hydroxyethyl arms of the macrocycle ligand are located at same sides of a reference plane defined by the nitrogen atoms and the phenyl groups of the macrocyclic ligand, forming a boat-like (syn) conformation. The dinuclear Pd(II) complexes 1 and 2 were treated with AgNO3 to convert into [Pd2L(NO3)2]2+, the interaction of which with AcMet-Ala [6] was studied by ESI mass spectrum, as Figs. S2–S3 show, both [Pd2L(NO3)(AcMet-Ala)]2+ and [Pd2L(AcMet-Ala)2]2+ were formed as mixed in equimolar ratio and the later species was unique one as twofold excess of the AcMet-Ala was used. The hydrolysis of Met-Ala bond in the complexes of [Pd2L(NO3)(AcMet-Ala)]2+ and [Pd2L(AcMet-Ala)2]2+ was monitored by 1H NMR via resonance of CH3 of Ala in AcMet-Ala and free alanine of hydrolytic product. The observed first-order rate constants are given in Table 1. In comparison with control experiment, the accelerated action of the two dinuclear Pd(II) complexes is noteworthy. The hydrolysis of Met-Ala bond in [Pd2L(AcMet-Ala)2]2+ is independently carried out by each Pd(II)-coordinated diethylenetriamine moiety. The effect of pH was examined and shown in Table 2, the observed rate constant for hydrolysis of Met-Ala bond in AcMet-Ala increases remarkably as the solution is more acidic. As previously reported [3b,3e,7], the Pd(trien)(H2O)2+ is unactive towards hydrolysis of methionine-containing peptides, as Scheme 1 shows, the hydrolysis of Met-Ala bond in [Pd2L(AcMetAla)2]2+ is obviously promoted by the pendent hydroxyl
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G. Yang et al. / Inorganic Chemistry Communications 8 (2005) 862–865
Table 1 Hydrolysis of Met-Ala bond in AcMet-Ala, promoted by dinuclear Pd(II) complex cations at pH* 1.0, and 50 ± 0.5 C 103kobsd (h 1)
Molar ratio promoter:AcMet-Ala
1 1:1 0.5:1 0:1 a
2
79.2 ± 0.7 61.2 ± 0.6 65.6 ± 0.4 53.1 ± 0.4 0.67 ± 0.01a
The detail procedures of some experiments concerning the hydrolysis of AcMet-Ala promoted by the two dinuclear Pd(II) complexes and Figs. S1–S5 are given in Supplementary material. Supplementary data associated with this article can be found, in the online version, at doi:10.1016/ j.inoche.2005.06.022.
Followed less than three half-lives.
Table 2 Effect of pH on hydrolysis of Met-Ala bond in AcMet-Ala, promoted by 0.5 eq. dinuclear Pd(II) complex cations at 50 ± 0.5 C 103kobsd (h 1)
pH*
1.5 1.0
1
2
25.5 ± 0.2 65.6 ± 0.4
18.9 ± 0.4 53.1 ± 0.4
O
H3C +
H3C
CH
HO
O H N
C
C
C
OH
NH
CH
H O
CH2 NH
H2C S H3C
Pd
N
NH
Scheme 1.
group and probably catalyzed by general acid. This investigation provides a clue to design new cleavage agents of peptides and proteins.
Acknowledgments This work was supported by the National Natural Science Foundation of China (Nos. 20271027 and 20231010).
Appendix A. Supplementary data Crystallographic data have been deposited in the Cambridge Crystallographic Data Centre with Deposition Nos. 273327 for 1 and 273328 for 2. Copies of the information can be obtained from the director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (fax: +44 1223 336 033; e-mail: [email protected] or www: http://www.ccdc.cam.ac.uk).
References [1] M.A. Smith, M. Easton, P. Everett, G. Lewis, M. Payne, V. Riveros-Moreno, G. Allen, Int. J. Pept. Protein Res. 48 (1996) 48. [2] W. Bal, R. Liang, J. Lukszo, S.-H. Lee, M. Dizdaroglu, K.S. Kasprzak, Chem. Res. Toxicol. 13 (2000) 616. [3] (a) L. Zhu, N.M. Kostic´, J. Am. Chem. Soc. 115 (1993) 4566; (b) X. Chen, L. Zhu, H. Yan, X. You, N.M. Kostic´, J. Chem. Soc., Dalton Trans. (1996) 2653; (c) G.B. Karet, N.M. Kostic´, Inorg. Chem. 37 (1998) 1021; (d) X. Chen, L. Zhu, X. You, N.M. Kostic´, J. Biol. Inorg. Chem. 3 (1998) 1; (e) X. Chen, X. Luo, Y. Song, S. Zhou, L. Zhu, Polyhedron 17 (1998) 2271. [4] (a) T.N. Parac, N.M. Kostic´, J. Am. Chem. Soc. 118 (1996) 5946; (b) T.N. Parac, G.M. Ullmann, N.M. Kostic´, J. Am. Chem. Soc. 121 (1999) 3127; (c) M.I. Djuran, S.U. Milinkovic´, Polyhedron 18 (1999) 3611; (d) X. Sun, L. Zhang, Y. Zhang, G. Yang, Z. Guo, L. Zhu, New J. Chem. 27 (2003) 818. [5] (a) N.M. Milovic´, N.M. Kostic´, J. Am. Chem. Soc. 124 (2002) 4759; (b) N.M. Milovic´, N.M. Kostic´, J. Am. Chem. Soc. 125 (2003) 781; (c) N.M. Milovic´, N.M. Kostic´, Inorg. Chem. 41 (2002) 7053; (d) L. Zhu, L. Qin, T.N. Parac, N.M. Kostic´, J. Am. Chem. Soc. 116 (1994) 5218; (e) L. Zhu, R. Bakhtiar, N.M. Kostic´, J. Biol. Inorg. Chem. 3 (1998) 383; (f) F. Qiao, J. Hu, H. Zhu, X. Luo, L. Zhu, D. Zhu, Polyhedron 18 (1999) 1629. [6] L. Zhu, N.M. Kostic´, Inorg. Chem. 31 (1992) 3994. [7] N.M. Milovic´, L.-M. Dutca˜, N.M. Kostic´, Inorg. Chem. 42 (2003) 4036. [8] (a) I.E. Burgeson, N.M. Kostic´, Inorg. Chem. 30 (1991) 4299; (b) M. Hahn, M. Kleine, W.S. Sheldrick, J. Biol. Inorg. Chem. 6 (2001) 556; (c) N.M. Milovic´, L.-M. Dutca˜, N.M. Kostic´, Chem. Eur. J. 9 (2003) 5097. [9] J. Chin, Acc. Chem. Res. 24 (1991) 145. [10] (a) D.F. Elliott, Biochem. J. 50 (1952) 542; (b) D.R. Corey, C.S. Craik, J. Am. Chem. Soc. 114 (1992) 1784. [11] S.-A. Li, J. Xia, D.-X. Yang, Y. Xu, D.-F. Li, M.-F. Wu, W.-X. Tang, Inorg. Chem. 41 (2002) 1807. [12] Synthesis of complex 1: A solution of 0.149 g (0.3 mmol) L and 15 mL water was added dropwise to an aqueous solution (25 mL) of K2PdCl4 (0.178 g, 0.6 mmol) with stirring. The reaction solution was heated at 60 C for 30 min, and then was filtered. To the filtrate was added 5 mL of NaClO4 saturated solution. After the resultant solution was stored in a 4 C refrigerator for 4 d, yellow block crystals were obtained and washed with water, yield 63%. Found (calcd.) % for C28H50Cl4N6O12Pd2: C, 33.29 (33.06); H, 4.76 (4.95); N, 8.46 (8.26). 1H NMR (d/ppm): 8.93 (br, 2.7H), 8.24 (s, 2.6H), 7.44
G. Yang et al. / Inorganic Chemistry Communications 8 (2005) 862–865 (br, 2.7H), 4.22–4.14 (m, 4H), 3.57–2.83 (m, 26H), 2.11 (t, J = 5.90 Hz, 2H). [13] M.S. Kharasch, R.C. Seyler, F.R. Mayo, J. Am. Chem. Soc. 60 (1938) 882. [14] Synthesis of complex 2: To a methanol solution of (50 mL) containing Pd(PhCN)2Cl2 (0.385 g, 1.0 mmol) was added a solution of 0.25 g (0.5 mmol) L in 15 mL methanol dropwise with stirring. The mixture was refluxed for 14 h. A solid was filtered off and a yellow solution was obtained. After removal of solvent in vacuo, the solid residue was dissolved in water, and the aqueous solution was filtered again. Then the filtrate was evaporated. After the concentrated solution was stored in a refrigerator for 10 days, yellow block crystals were obtained and washed with water, yield 79%. Found (calcd.) % for C28H50Cl4N6O4Pd2: C, 37.88 (37.81); H, 5.72 (5.67); N, 9.29 (9.45). 1H NMR (d/ppm): 8.93 (br, 4H), 7.44 (br, 4H), 4.20 (d, J = 13.07 Hz, 4H), 3.42–3.40 (m, 4H), 3.35 (t, J = 6.21 Hz, 4H), 3.23 (d, J = 13.14 Hz, 4H), 3.11 (m, 4H), 3.02–2.92 (m, 4H), 2.85 (m, 4H), 2.10 (t, J = 6.18 Hz, 4H). [15] Electrospray ionization (ESI) mass spectra were recorded using LCQ electrospray mass spectrometer (ESI–MS, Finnigan) by loading 1.0 lL solution into the injection valve of the LCQ unit and then injecting into the mobile phase solution (50% of aqueous methanol), which was carried through the electrospray interface into the mass analyzer at a rate of 200 lL min 1. The voltage employed at the electrospray needles was 4.5 kV, and the capillary was heated to 200 C. Positive ion mass spectra were obtained. Zoom scan and simulation of isotope distribution patterns using IsoPro 3.0 program were performed for each of the major species detected.
865
[16] Crystallographic data for 1: [C28H46Cl2N6O2Pd2](ClO4)2 Æ 2H2O, M = 1017.34, monoclinic, space group P21/c, a = 13.890 (3), ˚ , b = 98.99 (3), V = 1993.5 (7) A ˚ 3, b = 10.950 (2), c = 13.270 (3) A Z = 2, T = 293(2) K, Dc = 1.695 mg/m3, l = 1.233 mm 1, F(0 0 0) = 1032, crystal size = 0.20 · 0.20 · 0.30 mm. A total of 4052 reflections (1.5 6 h P 25.9) were collected, of which 3872 unique reflections were used for structural elucidation (Rint = 0.025). The final R1 was 0.0547 (all data). 2: [C28H46Cl2N6O2Pd2]Cl2 Æ 2H2O, M = 889.34, triclinic, space ˚, group P 1, a = 9.997(3), b = 13.719(3), c = 15.838 (4) A a = 108.254 (4), b = 91.181 (5), c = 106.224 (4), V = 1966.7(9) ˚ 3, Z = 2, T = 293 (2) K, Dc = 1.502 mg/m3, l = 1.224 mm 1, A F(0 0 0) = 904, crystal size = 0.22 · 0.24 · 0.33 mm. A total of 20,390 reflections (2.1 6 h P 25.5) were collected, of which 7151 unique reflections were used for structural elucidation (Rint = 0.013). The final R1 was 0.0452 (all data). The crystal data were collected on a Bruker-SMART CCD diffractometer equipped with graphite monochromatized Mo Ka radiation ˚ ). The structures were solved by direct methods, (k = 0.71073 A and refined by least-squares treatment on F2 using the SHELXTL software package. All non-hydrogen atoms were refined anisotropically by full-matrix least squares. All the H atoms were computed and refined isotropically using a riding model. [17] (a) S.-A. Li, D.-F. Li, D.-X. Yang, Y.-Z. Li, J. Huang, K.-B. Yu, W.-X. Tang, Chem. Commun. (2003) 880; (b) D.-F. Li, S.-A. Li, D.-X. Yang, J.-H. Yu, J. Huang, Y.-Z. Li, W.-X. Tang, Inorg. Chem. 42 (2003) 6071. [18] W. He, F. Liu, C. Duan, Z. Guo, S. Zhou, Y. Liu, L. Zhu, Inorg. Chem. 40 (2001) 7065.
Syntheses, structures, and properties of two dinuclear palladium (II) complexes of a single macrocyclic hexaaza ligand with two hydroxyethyl pendants Gaosheng Yang a
a,b
, Huiwei Tang a, Yizhi Li a, Jing Hong a, Zijian Guo a, Longgen Zhu
a,*
State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, Nanjing University, Nanjing 210093, China b College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241000, China Received 7 June 2005; accepted 21 June 2005 Available online 8 August 2005
Abstract Two dinuclear palladium (II) complexes, trans-[Pd2LCl2](ClO4)2 Æ 2H2O and cis-[Pd2LCl2]Cl2 Æ 2H2O, of a single macrocyclic ligand with two hydroxyethyl pendants, L (L = 3,6,9,16,19,22-hexaaza-6,19-bis(2-hydroxyethyl)tricyclo[22,2,2,211,14]triaconta1,11,13,24,27,29-hexaene), have been synthesized as ‘‘inorganic proteases’’ and analyzed by X-ray diffraction method. The two complexes-mediated hydrolytic cleavage of amide bond in acetyl methionyl alanine has been monitored by 1H NMR, showing a moderate hydrolytic rate at 50 C and pH ca. 1.0. The pendent hydroxyl group is responsible for the hydrolytic reaction. 2005 Elsevier B.V. All rights reserved. Keywords: Dinuclear palladium (II) complex; Macrocyclic hexaaza; ESI–MS; Inorganic proteases
Over the past decade, the site-specific non-enzymatic hydrolysis of amide bond in peptides and proteins has been attracting much attention [1–8]. To the best of our knowledge, the reported Pd(II) [3–7] and Pt(II) [6– 8] complexes, in nature, are mononuclear complexes, and at least an aqua ligand is required for activation of amide bond by delivery mechanism or for replacement of it by carbonyl oxygen via extra water attack mechanism [3a,5b–7,9]. However, in some serinecontaining peptidases, the hydroxyl group of serine plays key role in catalytic hydrolysis of amide bond in proteins [10]. To mimic the function, a single macrocyclic ligand with two hydroxyethyl pendants, L (L = 3,6, 9,16,19,22-hexaaza-6,19-bis(2-hydroxyethyl)tricyclo[22, 2,2,211,14]triaconta-1,11,13,24,27,29-hexaene) was used as ligand to synthesize two new dinuclear palladium *
Corresponding author. Tel.: +86 25 8359 7066; fax: +86 25 8331 4502. E-mail address: [email protected] (L. Zhu). 1387-7003/$ - see front matter 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.inoche.2005.06.022
(II) complexes for investigating their ability to hydrolysis of methionine-containing dipeptide. The ligand L was synthesized based on a published procedure [11]. Complex 1, trans-[Pd2LCl2](ClO4)2 Æ 2H2O, was obtained by reaction of L with two equivalents of K2PdCl4 in water at 60 C and crystallized as yellow block crystals from the aqueous solution after adding NaClO4 saturated solution and stored in a refrigerator [12]. However, reaction of L with two equivalents of trans-Pd(PhCN)2Cl2 [13] in methanol solution under reflux conditions generated complex 2, cis-[Pd2LCl2] Cl2 Æ 2H2O, which was recrystallized as yellow block crystals from a concentrated aqueous solution stored in a refrigerator [14]. ESI mass spectrum [15] of complexes 1 and 2 (Fig. S1) shows that the cations of two complexes have the same composition. The peak at m/z 391.0 with doubly positive charges was observed, corresponding to the species of [Pd2LCl2]2+. This species was confirmed by good agreement between the observed (Fig. S1(A)) and
G. Yang et al. / Inorganic Chemistry Communications 8 (2005) 862–865
calculated isotopic distribution pattern (Fig. S1(B)). Xray analysis [16] indicates that the macrocyclic ligands in the two complexes possess two different conformations, which can only be accomplished by stereochemical inversion at one (or more) of the nitrogen atoms (at least, one of the two tertiary nitrogen atoms) of the free macrocyclic ligand in the formation of the complexes [17]. The dinuclear Pd(II) complex 1 crystallizes in a monoclinic space group P21/c. The crystal structure of 1 consists of cationic unit of trans-[Pd2LCl2]2+, two non-coordinated perchlorate ions and two water molecules. A perspective view of the cationic complex is shown in Fig. 1. In the dinuclear Pd(II) complex, each Pd(II) is coordinated by diethylenetriamine moiety, with bond distances of Pd–N, from 2.031(4) to ˚ which are typical for this type of coordina2.076(4) A tion [18], and each Pd(II) ion adopts a distorted square configurations in the N3Cl environment. The distance ˚ . The two between the two Pd(II) ions is 7.088(2) A non-coordinated hydroxyethyl arms of the macrocycle ligand are located at opposite sides of the plane defined by the nitrogen atoms and the phenyl groups of the macrocyclic ligand. The cationic complex forms a chair-like (anti) conformation. Unlike 1, the dinuclear Pd(II) complex 2 crystallizes in a triclinic P 1. The asymmetric unit consists of a cis[Pd2LCl2]2+ cation, two counterpart chloride anions and two disordered water molecules occupying five positions in occupancy of 0.36(1), 0.40(1), 0.45(1), 0.47(1), 0.32(1), respectively. Fig. 2 shows the ORTEP drawing of the cationic complex. In the cationic complex, each Pd(II) ion has a distorted square configuration in the N3Cl environment. The two palladium ions
Fig. 1. ORTEP drawing of the cationic complex 1 with 30% thermal ellipsoids (the hydrogen atoms are omitted for clarity). Selected bond ˚ ): Pd–N1 2.031(4), Pd–N2 2.072(6), Pd–N3 2.076(4), Pd–Cl1 lengths (A 2.297(2); selected bond angles (): Cl1–Pd–N1 175.3(1), Cl1–Pd–N2 94.2(2), Cl1–Pd–N3 92.3(2), N1–Pd–N2 87.2(2), N1–Pd–N3 85.5(2), N2–Pd–N3 168.5(2).
863
Fig. 2. ORTEP drawing of the cationic complex 2 with 30% thermal ellipsoids (the hydrogen atoms are omitted for clarity). Selected bond ˚ ): Pd1–N1 2.030(4), Pd1–N2 2.024(3), Pd1–N3 2.051(5), lengths (A Pd1–Cl1 2.307(2), Pd2–N4 2.039(5), Pd2–N5 2.015(4), Pd2–N6 2.033(4), Pd2–Cl2 2.308(2); selected bond angles (): Cl1–Pd1–N1 94.6(1), Cl1–Pd1–N2 176.5(1), Cl1–Pd1–N3 94.5(1), N1–Pd1–N2 85.8(2), N1–Pd1–N3 165.1(2), N2–Pd1–N3 84.4(2), Cl2–Pd2–N4 95.8(1), Cl2–Pd2–N5 178.2(1), Cl2–Pd2–N6 94.0(1), N4–Pd2–N5 84.4(2), N4–Pd2–N6 164.8(2), N5–Pd2–N6 85.5(2).
˚ apart from each other. The two nonare 6.813(2) A coordinated hydroxyethyl arms of the macrocycle ligand are located at same sides of a reference plane defined by the nitrogen atoms and the phenyl groups of the macrocyclic ligand, forming a boat-like (syn) conformation. The dinuclear Pd(II) complexes 1 and 2 were treated with AgNO3 to convert into [Pd2L(NO3)2]2+, the interaction of which with AcMet-Ala [6] was studied by ESI mass spectrum, as Figs. S2–S3 show, both [Pd2L(NO3)(AcMet-Ala)]2+ and [Pd2L(AcMet-Ala)2]2+ were formed as mixed in equimolar ratio and the later species was unique one as twofold excess of the AcMet-Ala was used. The hydrolysis of Met-Ala bond in the complexes of [Pd2L(NO3)(AcMet-Ala)]2+ and [Pd2L(AcMet-Ala)2]2+ was monitored by 1H NMR via resonance of CH3 of Ala in AcMet-Ala and free alanine of hydrolytic product. The observed first-order rate constants are given in Table 1. In comparison with control experiment, the accelerated action of the two dinuclear Pd(II) complexes is noteworthy. The hydrolysis of Met-Ala bond in [Pd2L(AcMet-Ala)2]2+ is independently carried out by each Pd(II)-coordinated diethylenetriamine moiety. The effect of pH was examined and shown in Table 2, the observed rate constant for hydrolysis of Met-Ala bond in AcMet-Ala increases remarkably as the solution is more acidic. As previously reported [3b,3e,7], the Pd(trien)(H2O)2+ is unactive towards hydrolysis of methionine-containing peptides, as Scheme 1 shows, the hydrolysis of Met-Ala bond in [Pd2L(AcMetAla)2]2+ is obviously promoted by the pendent hydroxyl
864
G. Yang et al. / Inorganic Chemistry Communications 8 (2005) 862–865
Table 1 Hydrolysis of Met-Ala bond in AcMet-Ala, promoted by dinuclear Pd(II) complex cations at pH* 1.0, and 50 ± 0.5 C 103kobsd (h 1)
Molar ratio promoter:AcMet-Ala
1 1:1 0.5:1 0:1 a
2
79.2 ± 0.7 61.2 ± 0.6 65.6 ± 0.4 53.1 ± 0.4 0.67 ± 0.01a
The detail procedures of some experiments concerning the hydrolysis of AcMet-Ala promoted by the two dinuclear Pd(II) complexes and Figs. S1–S5 are given in Supplementary material. Supplementary data associated with this article can be found, in the online version, at doi:10.1016/ j.inoche.2005.06.022.
Followed less than three half-lives.
Table 2 Effect of pH on hydrolysis of Met-Ala bond in AcMet-Ala, promoted by 0.5 eq. dinuclear Pd(II) complex cations at 50 ± 0.5 C 103kobsd (h 1)
pH*
1.5 1.0
1
2
25.5 ± 0.2 65.6 ± 0.4
18.9 ± 0.4 53.1 ± 0.4
O
H3C +
H3C
CH
HO
O H N
C
C
C
OH
NH
CH
H O
CH2 NH
H2C S H3C
Pd
N
NH
Scheme 1.
group and probably catalyzed by general acid. This investigation provides a clue to design new cleavage agents of peptides and proteins.
Acknowledgments This work was supported by the National Natural Science Foundation of China (Nos. 20271027 and 20231010).
Appendix A. Supplementary data Crystallographic data have been deposited in the Cambridge Crystallographic Data Centre with Deposition Nos. 273327 for 1 and 273328 for 2. Copies of the information can be obtained from the director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (fax: +44 1223 336 033; e-mail: [email protected] or www: http://www.ccdc.cam.ac.uk).
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G. Yang et al. / Inorganic Chemistry Communications 8 (2005) 862–865 (br, 2.7H), 4.22–4.14 (m, 4H), 3.57–2.83 (m, 26H), 2.11 (t, J = 5.90 Hz, 2H). [13] M.S. Kharasch, R.C. Seyler, F.R. Mayo, J. Am. Chem. Soc. 60 (1938) 882. [14] Synthesis of complex 2: To a methanol solution of (50 mL) containing Pd(PhCN)2Cl2 (0.385 g, 1.0 mmol) was added a solution of 0.25 g (0.5 mmol) L in 15 mL methanol dropwise with stirring. The mixture was refluxed for 14 h. A solid was filtered off and a yellow solution was obtained. After removal of solvent in vacuo, the solid residue was dissolved in water, and the aqueous solution was filtered again. Then the filtrate was evaporated. After the concentrated solution was stored in a refrigerator for 10 days, yellow block crystals were obtained and washed with water, yield 79%. Found (calcd.) % for C28H50Cl4N6O4Pd2: C, 37.88 (37.81); H, 5.72 (5.67); N, 9.29 (9.45). 1H NMR (d/ppm): 8.93 (br, 4H), 7.44 (br, 4H), 4.20 (d, J = 13.07 Hz, 4H), 3.42–3.40 (m, 4H), 3.35 (t, J = 6.21 Hz, 4H), 3.23 (d, J = 13.14 Hz, 4H), 3.11 (m, 4H), 3.02–2.92 (m, 4H), 2.85 (m, 4H), 2.10 (t, J = 6.18 Hz, 4H). [15] Electrospray ionization (ESI) mass spectra were recorded using LCQ electrospray mass spectrometer (ESI–MS, Finnigan) by loading 1.0 lL solution into the injection valve of the LCQ unit and then injecting into the mobile phase solution (50% of aqueous methanol), which was carried through the electrospray interface into the mass analyzer at a rate of 200 lL min 1. The voltage employed at the electrospray needles was 4.5 kV, and the capillary was heated to 200 C. Positive ion mass spectra were obtained. Zoom scan and simulation of isotope distribution patterns using IsoPro 3.0 program were performed for each of the major species detected.
865
[16] Crystallographic data for 1: [C28H46Cl2N6O2Pd2](ClO4)2 Æ 2H2O, M = 1017.34, monoclinic, space group P21/c, a = 13.890 (3), ˚ , b = 98.99 (3), V = 1993.5 (7) A ˚ 3, b = 10.950 (2), c = 13.270 (3) A Z = 2, T = 293(2) K, Dc = 1.695 mg/m3, l = 1.233 mm 1, F(0 0 0) = 1032, crystal size = 0.20 · 0.20 · 0.30 mm. A total of 4052 reflections (1.5 6 h P 25.9) were collected, of which 3872 unique reflections were used for structural elucidation (Rint = 0.025). The final R1 was 0.0547 (all data). 2: [C28H46Cl2N6O2Pd2]Cl2 Æ 2H2O, M = 889.34, triclinic, space ˚, group P 1, a = 9.997(3), b = 13.719(3), c = 15.838 (4) A a = 108.254 (4), b = 91.181 (5), c = 106.224 (4), V = 1966.7(9) ˚ 3, Z = 2, T = 293 (2) K, Dc = 1.502 mg/m3, l = 1.224 mm 1, A F(0 0 0) = 904, crystal size = 0.22 · 0.24 · 0.33 mm. A total of 20,390 reflections (2.1 6 h P 25.5) were collected, of which 7151 unique reflections were used for structural elucidation (Rint = 0.013). The final R1 was 0.0452 (all data). The crystal data were collected on a Bruker-SMART CCD diffractometer equipped with graphite monochromatized Mo Ka radiation ˚ ). The structures were solved by direct methods, (k = 0.71073 A and refined by least-squares treatment on F2 using the SHELXTL software package. All non-hydrogen atoms were refined anisotropically by full-matrix least squares. All the H atoms were computed and refined isotropically using a riding model. [17] (a) S.-A. Li, D.-F. Li, D.-X. Yang, Y.-Z. Li, J. Huang, K.-B. Yu, W.-X. Tang, Chem. Commun. (2003) 880; (b) D.-F. Li, S.-A. Li, D.-X. Yang, J.-H. Yu, J. Huang, Y.-Z. Li, W.-X. Tang, Inorg. Chem. 42 (2003) 6071. [18] W. He, F. Liu, C. Duan, Z. Guo, S. Zhou, Y. Liu, L. Zhu, Inorg. Chem. 40 (2001) 7065.