Synthesis, characterization and reactivity of carbohydrate platinum(IV) complexes with thioglycoside ligands

Abstract

Reactions of fac-[PtMe₃(4,4′-R₂bpy)(Me₂CO)][BF₄] (R = H, 1a; ^tBu, 1b) and fac-[PtMe₃-(OAc-κ²O,O′)(Me₂CO)] (2), respectively, with thioglycosides containing thioethyl (ch-SEt) and thioimidate (ch-STaz, Taz = thiazoline-2-yl) anomeric groups led to the formation of the carbohydrate platinum(IV) complexes fac-[PtMe₃(4,4′-R₂bpy)(ch*)][BF₄] (ch* = ch-SEt, 8–14; ch-STaz, 15–23) and fac-[PtMe₃(OAc-κ²O,O′)(ch*)] (ch* = ch-SEt, 24–28; ch-STaz = 29–35), respectively. NMR (¹H, ¹³C, ¹⁹⁵Pt) spectroscopic investigations and a single-crystal X-ray diffraction analysis of 19 (ch-STaz = 2-thiazolinyl 2,3,4,6-tetra-O-benzoyl-1-thio-β-d-galactopyranose) revealed the S coordination of the ch-SEt glycosides and the N coordination of the ch-STaz glycosides. Furthermore, X-ray structure analyses of the two decomposition products fac-[PtMe₃(bpy)(STazH-κS)][BF₄] (21a) and 1,6-anhydro-2,3,4-tri-O-benzoyl-β-d-glucopyranose (23a), where a cleavage of the anomeric C–S bond had occurred in both cases, gave rise to the assumption that this decomposition was mediated due to coordination of the thioglycosides to the high electrophilic platinum(IV) atom, in non-strictly dried solutions. Reactions of fac-[PtMe₃(Me₂CO)₃][BF₄] (3) with ch-SEt as well as with ch-SPT and ch-Sbpy thioglycosides (PT = 4-(pyridine-2-yl)-thiazole-2-yl; bpy = 2,2′-bipyridine-6-yl), having N,S and N,N heteroaryl anomeric groups, respectively, led to the formation of platinum(IV) complexes of the type fac-[PtMe₃(ch*)][BF₄] (ch* = ch-SEt, 36–40, ch-SPT 42–44, ch-Sbpy 45, 46). The thioglycosides were found to be coordinated in a tridentate κS,κ²O,O′, κS,κN,κO and κS,κ²N,N′ coordination mode, respectively. Analogous reactions with ch-STaz ligands succeeded for 2-thiazolinyl 2,3,4-tri-O-benzyl-6-O-(2,2′-bipyridine-6-yl)-1-thio-β-d-glucopyranoside (5h) resulting in fac-[PtMe₃(ch-STaz)][BF₄] (41, ch-STaz = 5h), having a κ³N,N′,N″ coordinated thioglycoside ligand.

1. Introduction

Carbohydrates are one of the most important classes of biomolecules. Attached to lipids, proteins and nucleobases they exert versatile functions in living organisms, ranging from immune defence and cell growth to inflammation and malignant transformations.^1,2 Carbohydrate-based pharmaceuticals have been proven to be promising therapeutics for neurodegenerative diseases, because they can easily pass the blood brain barrier.³ Thiofunctionalized carbohydrates were proved to possess significant bioactivity. It was found that 5-thio-β-d-glucopyranose, where the ring oxygen is replaced by sulfur, can cause temporary diabetes and sterility in rats.⁴ Moreover, this carbohydrate class, having a ring sulfur atom, exhibit cancerostatic properties⁵ and act as enzyme inhibitors.⁶ Up to now, it has also been shown that thioglycosides and carbohydrates with mercapto groups instead of hydroxyl groups are enzyme inhibitors and thereby possess antiproliferative and anti-inflammatory properties.⁷ Metal-coordination of carbohydrates also plays a significant role in biosyntheses, including metal transportation and storage or the regulation of metalloenzymes.^8,9 Furthermore, metal–carbohydrate complexes have been investigated as potent radiopharmaca¹⁰ and cancerostatica, where platinum compounds are of considerable interest.¹¹ From a coordination chemistry perspective the syntheses of carbohydrate platinum(IV) complexes, particularly with non-functionalized carbohydrate ligands, represent a notable challenge, due to their weak donor ability and their propensity to act as reducing agents.¹² On the other hand, platinum(IV) complexes are kinetically inert due to the low-spin d⁶ electron configuration, so substitution reactions are not favored. However, numerous platinum(IV) complexes with neutral carbohydrate ligands have been synthesized using trimethylplatinum(IV) precursor complexes such as fac-[PtMe₃(Me₂CO)₃][BF₄]. Complexes of this type have proven especially useful in this respect because the high donor capability of the methyl ligands stabilizes the platinum(IV) oxidation state. Furthermore, the leaving ligands (acetone) are only weakly coordinated and their substitution is additionally facilitated by the high trans effect of the methyl ligands.¹³ Herein we present the synthesis, characterization and reactivity of various types of trimethylplatinum(IV) complexes with thioglycoside ligands.

2. Results and discussion

2.1. Starting complexes and ligands

For the synthesis of trimethylplatinum(IV) complexes with thioglycoside ligands, starting complexes having up to three substitution-labile ligands were used. Complexes with one substitution-labile acetone ligand, fac-[PtMe₃(Me₂CO)(bpy)][BF₄] (1a) and fac-[PtMe₃(Me₂CO)(4,4′-^tBu₂bpy)][BF₄] (1b; Scheme 1), were prepared by the reaction of fac-[PtMe₃I(bpy)] and fac-[PtMe₃I(4,4′-^tBu₂bpy)], respectively, with Ag[BF₄].¹⁴ The reaction of the tetranuclear heterocubane complex fac-[(PtMe₃I)₄] with AgOAc resulted in the formation of fac-[PtMe₃(OAc)(Me₂CO)_n] (2). The acetato ligand can be bidentately or monodentately coordinated (OAc-κ²O,O′, n = 1; OAc-κO, n = 2). DFT calculations showed that the free energy at 298 K of the reaction

$$\mathit{\text{fac}}-[{\text{PtMe}}_3(\text{OAc}-\mathrm{\kappa }O){({\text{Me}}_2\text{CO})}_2]\rightleftharpoons \mathit{\text{fac}}-[{\text{PtMe}}_3(\text{OAc}-{\mathrm{\kappa }}^{2}O,O\prime )({\text{Me}}_2\text{CO})]+{\text{Me}}_2\text{CO}$$

amounts to be −44 kJ mol⁻¹ in the gas phase and −61 kJ mol⁻¹ in acetone. This gives proof that the acetato ligand is bidentately bound. Nevertheless, both complexes have at their disposal up to three substitution-labile coordination sites, namely one when the acetone ligand is cleaved off and the acetato ligand is still coordinated in a chelating binding fashion, two when the acetone ligand is cleaved off and the acetato ligand remains to be κ¹O coordinated or three in the case of complete cleavage of the acetato ligand.

Scheme 1.

Platinum(IV) precursor complexes and β-D-thioglycosides used as ligands. ^a β-d-Galactose: OR at C4 in axial position. ^b Abbreviations: ch-STaz: Taz = thiazoline-2-yl; ch-SPT: PT = 4-(pyridine-2-yl)-thiazole-2yl; ch-Sbpy: bpy = 2,2′-bipyridine-6-yl. ^c pic: 2-picoline-2-yl. ^d bpy_−H: 2,2′-bipyridine-6-yl.

The analogous reaction of fac-[(PtMe₃I)₄] with Ag[BF₄] led to fac-[PtMe₃(Me₂CO)₃][BF₄] (3; Scheme 1), which possesses three substitution-labile acetone ligands.¹³ It should be noted that all complexes described here were synthesized in situ and used directly for reactions with thioglycosides which are summarized in Scheme 1. Four different classes of thioglycosides have been investigated, namely those with SEt anomeric groups ch-SEt (4a–f) and those having N,S or N,N heterocyclic anomeric groups: ch-STaz (5a–h; Taz = thiazoline-2-yl), ch-SPT (6a–c; PT = 4-(pyridine-2-yl)-thiazole-2-yl) and ch-Sbpy (7a,b; bpy = 2,2′-bipyridine-6-yl).

2.2. Cationic platinum(IV) complexes with monodentately coordinated thioglycoside ligands

Syntheses and X-ray diffraction analysis

Complexes 1a and 1b reacted in acetone with stoichiometric amounts of thioglycosides of type 4 and 5 (Scheme 1) yielding ionic complexes of the type fac-[PtMe₃(4,4′-R₂bpy)(ch-SEt-κS)][BF₄] (R = H: 8–11; R = ^tBu: 13, 14) and fac-[PtMe₃(4,4′-R₂bpy)(ch-STaz-κN)][BF₄] (R = H: 17–23; R = ^tBu: 15, 16), respectively (Scheme 2, Table 1). The complexes were isolated as moderately air-stable yellow and white powders, respectively, in yields of 45–94%. All complexes were characterized by ¹H, ¹³C and ¹⁹⁵Pt NMR spectroscopy as well as by IR spectroscopy, high resolution ESI mass spectrometry and in the case of 19 also by X-ray diffraction analysis.

Scheme 2.

Syntheses of carbohydrate platinum(IV) complexes fac-[PtMe₃(4,4′-R₂bpy)(ch*)][BF₄] (ch* = ch-SEt, R = H 8–11, R = ^tBu 13, 14; ch-STaz, R = H 17–23, R = ^tBu 15, 16).

Table 1.

¹H and ¹³C NMR spectroscopic data (δ in ppm, J in Hz) of the methyl ligands and ¹⁹⁵Pt chemical shifts of the complexes fac-[PtMe₃(bpy)(ch*)][BF₄] (8–12; 17–23) and fac-[PtMe₃(4,4′-^tBu₂bpy)(ch*)][BF₄] (13–16)

		δH		δC		1JPt,C		2JPt,H
Complex	ch*	trans ch*	trans Nbpy	trans ch*	trans Nbpy	trans ch*	trans Nbpy	trans ch*	trans Nbpy	δPt
	ch-SEt
8	4a	0.66	1.09	5.8	−5.0/−5.1	662.0	657.0./658.3	72.0	67.8	−2772
9	4b	0.65	1.09/1.11	5.1	−5.1/−5.4	652.0	662.0/654.5	71.6	69.3/67.8	−2529
10	4c	0.71	1.16	5.4	−4.5/−4.7	660.0	657.3/662.8	72.3	67.5	−2447
11	4d	0.64	1.14/1.16	5.1	−5.1/−5.2	649.5	663.2/662.0	71.0	66.9/66.9	−2446
12	4e	0.68	1.18/1.19	5.2	−4.6/−4.7	648.4	662.2/661.5	71.1	67.4/67.4	−2469
13	4a	0.66	1.03/1.10	5.8	−5.2/−5.3	647.1	659.4/664.6	72.6	66.4/67.1	−2769
14	4c	0.59	1.04	5.8	−5.0/−5.2	658.3	655.8/662.0	72.2	68.2	−2435
	ch-STaz
15	5c	0.53	1.13	−5.4	−3.3	678.2	675.7	71.4	68.1	−2716
16	5g	0.32	0.83/1.02	−6.1	−3.2/−4.7	676.6	667.0/684.4	72.5	67.6/66.9	−2452
17	5a	0.45	1.13/1.17	−5.5	−3.2/−4.2	673.1	677.0/677.8	72.2	68.5/67.2	−2730
18	5b	0.38	0.93/1.08	−5.7	−3.6	672.4	676.2	72.2	67.2/67.2	−2683
19	5c	0.39	0.93/1.08	−5.7	−3.6/−4.2	674.4	678.2/676.9	72.2	67.2/68.1	−2710
20	5d	0.45	1.21/1.23	−5.7	−3.7/−4.0	674.3	679.4/679.3	72.2	67.2/68.1	−2695
21	5e	0.42	1.18/1.19	−5.5	−4.0/−4.1	673.8	680.6/680.7	72.2	67.2/68.1	−2704
22	5f	0.42	1.19	−5.6	−3.7/−4.1	677.5	679.4/679.8	72.2	68.1	−2444
23	5g	0.37	0.93/1.06	−5.7	−3.6/−4.2	678.5	679.4/675.6	72.2	67.2/67.2	−2445

Small colorless needles of fac-[PtMe₃(bpy)(ch-STaz)][BF₄] (19; ch-STaz = 5c) were formed in an acetone solution layered with tetrahydrofuran and diethyl ether. Complex 19 crystallized in the chiral space group P4₁2₁2. The asymmetric unit consists of two symmetry independent fac-[PtMe₃(bpy)(ch-STaz)]⁺ (ch-STaz = 5c) cations, and two [BF₄]⁻ anions, wherein one exhibits a disorder. In Fig. 1, only one of the cations is illustrated, whereas the other one exhibits a similar structure. Selected bond lengths and angles are given in the figure caption. In complex 19 the platinum atom [PtC₃N₃] is octahedrally coordinated by three methyl ligands in facial arrangement, a bipyridine ligand and the thiazoline-2-yl ring, which is coordinated via the nitrogen atom. The angle between the thiazoline-2-yl ring and the equatorial [PtC₂N₂] plane is nearly perpendicular (86.5/89.8°^‡). The Pt–N bond length (2.16(1)/2.17(2) Å) belongs to the longest bonds known for Pt(IV)–N(CH₂)=C complexes (median: 2.139 Å, lower/upper quartile: 2.049/2.163 Å, n = 36; n – number of observations¹⁵), likely due to the high trans influence of the methyl ligands.^13,16 The STaz ring exhibits a distorted half-chair conformation, while the pyranose ring assumes a distorted chair conformation.¹⁷ A complex hydrogen bond network of moderate to weak inter- and intramolecular hydrogen bonds of the types C–H ⋯ O, C–H ⋯ F and C–H ⋯ S, respectively, is found in crystals of 19.

Fig. 1.

Molecular structure of one of the two crystallographically independent cations of fac-[PtMe₃(bpy)(ch-STaz-κN)][BF₄] (19, ch-S-Taz = 5c). Hydrogen atoms are omitted for clarity. The ellipsoids are drawn at the 30% probability level. Selected bond lengths (in Å) and angles (in °)^a: Pt–C1 2.14(2)/2.03(1), Pt–C2 1.98(1)/2.07(2), Pt–C3 2.02(2)/2.05(2), Pt–N3 2.16(1)/2.17(2), N3–C4 1.30(2)/1.33(2), C4–S2 1.73(2)/1.67(2), C1_ch–S2 1.85(2)/1.82(2), C1_ch–C2_ch 1.55(2)/1.64(2), C2_ch–C3_ch 1.51(2)/1.56(2), C3_ch–C4_ch 1.44(2)/1.54(2), C4_ch–C5_ch 1.43(2)/1.70(2), C5_ch–O1 1.41(2)/1.51(2), C1_ch–O1 1.42(2)/1.42(2), C1–Pt1–C2 88.8(6)/84.5(8), C2–Pt1–N3 179.5(6)/174.0(8), C3–Pt1–N2 175.3(6)/177.2(6), C4–S2–C1_ch 104.6(8)/101.8(9), C1_ch–O1–C5_ch 111(1)/117(1), O1–C1_ch–C2_ch 111(2)/111(2), C1_ch–C2_ch–C3_ch 104(1)/107(1), C2_ch–C3_ch–C4_ch 113(2)/117(2), C4_ch–C5_ch–O1 116(1)/104(1).^a The values of the two symmetry independent molecules are given separated by a slash.

NMR spectroscopic characterization of the complexes 8–23

The ¹H and ¹³C NMR spectra of complexes 8–23 showed unambiguously the coordination of the thioglycosides. Due to the coordination of the chiral carbohydrates to the platinum atom the complexes exhibited C₁ symmetry. Thus, a double signal set for the two halves of the bipyridine ligand, as along with the methyl ligands in trans position to the bipyridine ligand could be observed (Table 1). However, the chemical shifts of the methyl ligands were still very similar, leading to coincidence of signals for some compounds (Table 1). Coordination of the carbohydrates in complexes 8–23 led to a partial broadening of the signals of the carbohydrate protons and carbon atoms at room temperature, which has been proven to be characteristic for carbohydrate coordination also in other carbohydrate platinum(IV) complexes.¹³ A general shift of the resonances of the carbohydrate protons to higher field was observed for the complexes 8–23. Furthermore, the shift differences of the signals for the two protons belonging to the CH₂ groups of the SEt and STaz moieties were significantly increased due to the coordination to the platinum atom. On the other hand, only marginal coordination-induced shifts (CIS ≤ 1.6 ppm) for the resonances of the pyranose ring carbon atoms could be found.

In the case of complexes 8–11, 13 and 14 the S coordination of the SEt group gave rise to upfield shifts of the CH₂ proton signals of the SEt group up to 0.32 ppm and of the H1 protons up to 0.11 ppm. Interestingly, the coordination-induced shifts both of the carbon atom resonances of the Et group and of the anomeric C atom resonances were small (≤ 1.0 ppm) with the exception of complex 11, where the carbon atom of the methylene group was shifted upfield by 1.9 ppm. For complex 12, wherein thioglycoside 4e, having an additional N-donor site (picoline-2-yl), was used, the coordination mode could not be unambiguously assigned. On the one hand, the picoline-2-yl resonances in the ¹H and ¹³C NMR spectra are shifted downfield up to 0.2 and 2.4 ppm, respectively, which indicated an N coordination. Conversely, the broadening and increase of the shift differences for the signals of the CH₂ group of the SEt moiety in the ¹H NMR spectrum, as well as the ¹J_Pt,C coupling constant of the methyl ligand in trans position to the thioglycoside ligand of 648.4 Hz, indicated an S coordination.

In the case of complexes 15–23 the κN coordination of the STaz moiety has been proven unambiguously by the X-ray structure analysis of complex 19. Comparison of ¹H and ¹³C NMR data of complex 19 with those of the other complexes clearly demonstrated that the complexes 15–18 and 20–23 also possess bound κN coordinated ligands. Without the structural information on complex 19 it would be impossible to derive the coordination mode solely based on the NMR data. The signals for the NCH₂ and H1 protons showed the greatest CIS’s (up to 0.98 ppm and 0.57 ppm, respectively). On the other hand, the carbon atom resonances of the SCH₂ groups were strongly shifted upfield (up to 3.4 ppm), whereas the carbon atom resonances of the NCH₂ groups were only marginally shifted (up to 0.4 ppm).

The ¹H and ¹³C NMR signals of the methyl ligands trans to the thioglycoside ligands of type 4 were found in the range of 0.59–0.71 and 5.1–5.8 ppm, respectively. The requisite signals in complexes 15–23 with carbohydrate ligands of type 5 were found upfield shifted, with the shifts ranging from 0.32–0.53 ppm and −5.4 to −6.1 ppm, respectively. It had been shown, that the ¹J_Pt,C coupling constants in complexes of this type can be regarded to be a measure for the trans influence.¹⁶ The comparison of the ¹J_Pt,C couplings constants of the methyl ligands trans to the carbohydrate ligands in complexes 8–14 (647.1–662.0 Hz) with those in complexes 15–23 (672.4–678.5 Hz) indicated a higher trans influence of the thioglycosides with the SEt group than that of the respective STaz functionalized glycosides. Comparison with data given in the literature revealed that SEt carbohydrates in 8–14 possess a similar trans influence like in analogous platinum(IV) complexes having thionucleobase ligands fac-[PtMe₃(bpy)L][BF₄] (L = SCy, 1-MeSCy, s⁴Ura, s²s⁴Ura; ¹J_Pt,C: 642.1–651.5 Hz).¹⁸ The respective values in the complexes 15–23 were also found in accordance with those observed for trimethyl platinum(IV) complexes having N-bound ligands like 2-(methylthio)-2-thiazoline and pyrrazole in trans position (¹J_Pt,C: 675.4, 682.3 Hz).^{19 195}Pt chemical shifts for complexes 8–23 (Table 1) were found to be in the same range as for other trimethyl(bipyridine)platinum(IV) complexes.^16,18 Between complexes 8–14 (−2435 to −2772 ppm) and 15–23 (−2444 to −2730 ppm) no distinct shift differences were found. Thus, differences in the donor strength of the carbohydrate ligands seems to be too small to be clearly reflected in the δ_Pt values.

On the decomposition of the carbohydrate platinum(IV) complexes

Under strictly dehydrated conditions solutions of the complexes 8–23 were stable over weeks. Within two to three months only a slow decomposition with formation of platinum black took place, as indicated by NMR spectroscopy. In contrast, solutions in acetone, which were not strictly dehydrated, were found to be less stable. Thus, a solution of fac-[PtMe₃(bpy)(ch-STaz-κN)][BF₄] (21, ch-STaz = 5e) was found to decompose with the formation of well-shaped crystals, which were suitable for X-ray diffraction analysis. The compound 21a crystallized in the space group P2₁/c. The asymmetric unit consists of a fac-[PtMe₃(bpy)(STazH-κS)]⁺ cation and a disordered tetrafluoroborate anion. The molecular structure of the cation of 21a is shown in Fig. 2. Selected bond lengths and angles are given in the figure caption. The primary donor set [PtC₃N₂S] of the octahedrally coordinated platinum atom is built up by three methyl ligands in facial arrangement, the bipyridine ligand and the thiazolidine-2-thione (STazH) ligand, which is coordinated via the exocyclic sulfur atom to the platinum atom. The five membered heterocycle possesses a distorted half chair conformation along the C12–C13 bond, based on the torsion angle concept.¹⁷ Compared to the C=S bond in the free ligand (1.671–1.680 Ų⁰) no significant coordination-induced lengthening can be observed. Thus, the C11–S bond (1.683(4) Å) in complex 21a exhibits double bond character. In accordance with the high trans influence of the methyl ligands, the Pt1–S1 bond length (2.4818(9) Å) belongs to the longest ones known, as compared with thioketone platinum(IV) complexes (median: 2.372 Å, lower/upper quartile: 2.312/2.474 Å n = 9,¹⁵). The interplanar angle between the STazH ligand and the equatorial [PtC₂N₂] plane is 75.7°. As shown in Fig. 3, cation–anion interactions in crystals of 21a are related to hydrogen bond interactions of the type N3–H ⋯ F2 (N3 ⋯ F2 2.854(4) Å). Furthermore, molecules of 21a are packed like a “staircase” in infinite columns (Fig. 3). The distances between the bpy ligands (3.79/3.81 Å) together with the displacement^§ angle of 26.2° and 25.1°, respectively, indicated a weak stabilization through π–π and/or σ–π (C–H ⋯ π) interactions.²¹

Fig. 2.

Molecular structure of the cation of fac-[PtMe₃(bpy)-(STazH-κS)][BF₄] (21a). The ellipsoids are drawn at the 30% probability level. Selected bond lengths (in Å) and angles (in °): Pt–C15 2.050(3), Pt–C16 2.048(3), Pt–C14 2.046(3), Pt–N1 2.155(2), Pt–N2 2.163(3), Pt–S1 2.4818(9), C11–S1 1.683(4), N1–Pt–N2 76.4(1), C15–Pt–C16 85.5(2), C14–Pt–N2 90.0(1), S1–Pt–C14 172.12(9), C15–Pt–N1 173.9(1), C11–S1–Pt 117.0(1).

Fig. 3.

Solid state structure of fac-[PtMe₃(bpy)(STazH-κS)][BF₄] (21a) showing the packing of the cations by π–π stacking (---) and the hydrogen bonds (⋯) between cations and anions. Hydrogen atoms are omitted for clarity. Only one of the two disordered positions of the fluorine atoms are shown.

Most likely, complex 21a is a product of the hydrolysis of 21, which was induced by traces of water in the reaction mixture, followed by an isomerization (Scheme 3(a)). The cleavage of the glycosidic bond in 21 gave proof for the platinum mediated activation of the glycosidic bond due to coordination to the electrophilic cationic Pt(IV) center. Another indication for this is the product of hydrolysis, obtained in the reaction of complex 1a with 2-thiazolinyl 2,3,4-tri-O-benzoyl-1-thio-β-d-glucopyranose (5g). Crystals of a decomposition product (1,6-anhydro-2,3,4-tri-O-benzoyl-β-d-glucopyranose, 23a) were obtained from the acetone mother liquor. X-Ray diffraction analysis revealed that 23a crystallizes in the space group P1. The unit cell consists of two symmetry independent, but structurally very similar, molecules. The molecular structure of one molecule is depicted in Fig. 4. Selected bond lengths and angles are given in the figure caption. The pyranose ring possesses a distorted chair conformation on O1 and C3, while the five membered ring exhibits an envelope conformation on O1.¹⁷ The anhydro moiety was most likely formed due to an intramolecular nucleophilic attack of the oxygen atom O6 belonging to the unprotected hydroxyl group at C6, whereas the glycosidic bond was activated by platinum coordination, as discussed above (Scheme 3(b)).

Scheme 3.

Possible mechanisms for the decomposition of 21 to 21a (a) and 23 to 23a (b).

Fig. 4.

Molecular structure of one of the two symmetry independent molecules of 1,6-anhydro-2,3,4-tri-O-benzoyl-β-d-glucopyranose (23a). Hydrogen atoms are omitted for clarity. Ellipsoids are drawn at the 30% probability level. Selected bond lengths (in Å) and angles (in °)^a: O1–C5 1.425(5)/1.433(1), O1–C1 1.423(4)/1.417(5), O2–C1 1.417(4)/1.417(4), O2–C6 1.436(5)/1.439(4), C5–C6 1.533(5)/1.516(4), C1–C2 1.541(6)/1.507(7), C2–C3 1.513(6)/1.505(6), C3–C4 1.559(6)/1.554(6), C4–C5 1.523(6)/1.507(5), O1–C5–C6 102.2(3)/101.7(2), O2–C6–C5 103.5(3)/104.0(3), C1–O2–C6 107.1(3)/106.1(3), O1–C1–O2 106.1(3)/106.2(3), C1–O1–C5 102.2(3)/101.2(2), C2–C3–C4 113.4(4)/112.7(4), O1–C5–C4 108.7(3)/109.2(2), C5–C4–C3 111.7(3)/111.0(3), C3–C2–C1 112.2(3)/113.2(3), C2–C1–O1 109.3(3)/110.5(3). ^a The values of the two symmetry independent molecules are given separated by a slash.

2.3. Neutral platinum(IV) complexes with monodentately coordinated thioglycoside ligands

Synthesis and NMR spectroscopic characterization

The reaction of fac-[PtMe₃(OAc-κ²O,O′)(Me₂CO)] (2) with carbohydrate ligands of type 4 and 5 (Scheme 1) led to the formation of the complexes fac-[PtMe₃(OAc-κ²O,O′)(ch*)] (ch* = ch-SEt 24–28; ch-STaz 29–35) (Scheme 4, Table 2). The yellow, white and beige powders, respectively, are moderately air stable and were isolated in yields of 35–89%. The identities of the complexes 24–35 were confirmed by ¹H, ¹³C and ¹⁹⁵Pt NMR spectroscopy as well as by IR spectroscopy and high resolution ESI mass spectrometry.

Scheme 4.

Syntheses of carbohydrate platinum(IV) complexes fac-[PtMe₃(OAc-κ²O,O′)(ch*)] (ch* = ch-SEt, 24–28; ch-STaz, 29–35).

Table 2.

Selected NMR and IR spectroscopic data (δ in ppm, J in Hz, ν in cm⁻¹) of the complexes fac-[PtMe₃(OAc-κ²O,O′)(ch*)] (24–35)

Complex	ch*	δHa	δCa	2JPt,Ha	δPt	νsym. (CO2)	νasym. (CO2)	ΔνCO2
	ch-SEt
24	4a	1.08	−11.2	77.2	−2175	1411	1535	124
25	4b	1.07	−11.7	78.0	−2174	1411	1560	149
26	4c	1.10	−11.4	77.2	−2173	1409	1550	141
27	4d	0.96	−11.3	75.1	−2149	1404	1571	167
28	4e	1.15b	−10.3	76.4	−2444	1402	1568	166
	ch-STaz
29	5a	1.00	−11.7	77.8	−1910		1534
30	5b	0.91c	−11.1	77.2c	−1921	1411
31	5c	0.87	−11.3	73.0	−1918	1409	1535	126
32	5d	1.17	−11.3	74.4	−1907	1418	1552	134
33	5e	1.07	−11.4	75.6	−1904		1533
34	5f	1.08	−11.3	76.4	−1911	1411
35	5g	0.91	−11.5	76.4	−1916		1531

^aChemical shifts and coupling constants refer to the methyl ligands.

^bAt −80 °C: 0.98/0.92 ppm.

^cAt −50 °C: 0.72/0.78 ppm (74.4/70.4 Hz).

In the ¹H NMR spectra, the signals of the PtMe₃ protons exhibited broad mean signals at 0.87–1.17 ppm flanked by platinum satellites (singlet plus doublet). The requisite signals in the ¹³C NMR spectra for 24–35 were found as broad mean singlets. The chemical shifts (δ_H/δ_C) and coupling constants (²J_Pt,H) are assembled in Table 2. ¹H NMR measurements at −50 °C of the selected samples 28 and 30 showed that the expected split into three separate signals becomes apparent, although a broadening of the signals can be still observed. In the case of trimethylplatinum(IV) complexes with non-functionalized carbohydrate ligands at lower temperatures, three separated sharp signals were observed.¹³ As discussed in the previous section, some ¹H and ¹³C NMR signals of the carbohydrate ligands in the complexes 24–35 are also broadened. In contrast to the previously discussed fac-[PtMe₃(4,4′-R₂bpy)(ch-SEt-κS)][BF₄] (8–11, 13, 14) complexes, only marginal CIS’s up to 0.12 ppm could be observed for the signals of the CH₂ groups of the SEt moieties in the ¹H NMR spectra of the complexes 24–27, having ch-SEt ligands. The chemical shifts for the signals of H1 of the carbohydrate backbones were shifted up to 0.10 ppm. The corresponding CIS’s for the carbon atoms of the SEt groups and C1 resonances in the ¹³C NMR spectra amount up to 1.3 ppm and 1.7 ppm, respectively. For complex 28, where the ch-SEt ligand 4e possesses at C6 an additional N-donor-site (picoline-2-yl), NOE experiments at −80 °C were performed to examine whether the nitrogen atom is involved in the coordination to platinum. Irradiation into the resonance for H6 of the picoline-2-yl group led to an increase of intensity for one signal of the PtMe₃ moiety, stating the spatial surrounding. Thus, a coordination of the nitrogen atom of picoline-2-yl to the platinum atom is likely. In accordance with this, signals of the picoline-2-yl groups were shifted downfield in ¹H and ¹³C NMR spectra up to 0.24 and 2.1 ppm, respectively. Furthermore, the ¹⁹⁵Pt chemical shift of complex 28 was found to be about 270 ppm highfield shifted compared to those of complexes 24–27 (−2444 ppm versus −2149 to −2175 ppm, Table 2). However, a fast exchange between N and S coordination in solution could not be definitely ruled out, as indicated by the resonance downfield shift of 0.8 ppm for the CH₂ carbon atom signal of the SEt moiety.

The complexes with type 5 ligands fac-[PtMe₃(OAc-κ²O,O′)(ch-STaz)] (29–35) showed remarkable upfield shifts for the signals of H1 (0.34–0.50 ppm). The shift differences in ¹H NMR spectra of the two methylene proton resonances of the SCH₂ (up to 0.21 ppm) and NCH₂ (up to 0.30 ppm) were increased in complexes 24–28. Furthermore, upfield shifts ranging from 2.5–3.2 ppm were observed in the ¹³C NMR spectra for the signals of the carbon atoms of the SCH₂ groups (except 35). This indicated an N coordination of the STaz groups, because the complexes fac-[PtMe₃(bpy)(ch-STaz-κN)][BF₄] (15–23), where this coordination mode could be unambiguously proved, showed analogous features. ¹⁹⁵Pt NMR chemical shifts of all these complexes between −1910 and −2444 ppm (Table 2) are in the expected range for trimethylplatinum(IV) complexes.^13,16

High resolution ESI mass spectrometry

High resolution ESI mass spectrometric measurements were performed for complexes 24–35, which showed in all cases the existence of the molecular cation fac-[PtMe₃(ch*)]⁺_−OAc (ch* = ch-SEt, 4a–4e; ch-STaz; 5a–5g), exhibiting an isotopic envelope characteristic for monocations containing one platinum atom [natural isotopic composition: ¹⁹⁰Pt (0.01%), ¹⁹²Pt (0.79%), ¹⁹⁴Pt (32.9%), ¹⁹⁵Pt (33.8%), ¹⁹⁶Pt (25.3%) and ¹⁹⁸Pt (7.2%)]. The observed isotopic patterns of the molecular cations were in very good agreement with the calculated values. In Fig. 5, the full scan mass spectrum and the expanded spectrum of fac-[PtMe₃(ch-SEt)]⁺ (complex [28 − OAc]⁺; ch-SEt = 4e) is shown as an example. Furthermore, other peaks could be detected, which were assigned to be dinuclear complexes fac-[(PtMe₃)₂(OAc)(4e)]⁺ at 1124.3432 m/z, fac-[PtMe₃(4e)₂]⁺ at 1410.5450 m/z and fac-[(PtMe₃)₂(OAc)(4e)₂]⁺ at 1708.5787 m/z. According to the NMR spectra, in which the presence of such species can be clearly excluded, these species are formed during the ionization process and/or result from thermal decomposition during the ESI experiment.

Fig. 5.

(a) Positive ESI-mass spectrum of fac-[PtMe₃(ch-SEt)]⁺ (complex [28 − OAc]⁺; ch-SEt = 4e). (b) Isotopic pattern of the molecular ion fac-[PtMe₃(4e)]⁺ at 825.2871 m/z showing the expected intensity due to the isotopic composition given by horizontal bars.

IR spectroscopy

IR spectra were recorded to examine the coordination mode of the acetato ligand. The separation (Δν_CO2) between the symmetric and asymmetric stretching band is a suitable tool to distinguish between the different coordination modes.²² Typical Δν_CO2 values for a monodentate coordination are in general much higher (215–565 cm^{−1 22}) than those observed in ionic acetates (164–171 cm⁻¹ in MOAc, M = alkaline metal²²). On the other hand, a chelating coordination mode gives rise to Δν_CO2 values, which are similar or significantly lower (65–175 cm^{−1 22}) in comparison to those for ionic compounds. The stretching frequencies for the asymmetric and symmetric vibrational bands and the differences of those frequencies (Δν_CO2) for the complexes 24–35 are given in Table 2. For the fac-[PtMe₃(OAc-κ²O,O′)(ch-SEt)] complexes 24–28, Δν_CO2 amounts to 124–167 cm⁻¹, indicating a chelating coordination mode of the acetato ligand. In the case of the fac-[PtMe₃(OAc-κ²O,O′)(ch-STaz)] complexes 29–35, the assignment of the carboxyl stretching bands is often difficult because of the overlap with the absorption bands of the STaz moiety. Only for complexes 31 and 32 have both the symmetric and asymmetric vibrational bands been assigned unambiguously. The separation by 126 (31) and 134 cm⁻¹ (32), respectively, indicated a chelating coordination mode of the acetato ligand. As shown in Table 2, in the other complexes (29, 30, 33–35) the position of either ν_asym or ν_sym is in the same range as that observed in complexes 24–28, 31 and 32. Hence, the analogous coordination mode is likely.

2.4. Cationic platinum(IV) complexes with tridentately coordinated thioglycoside ligands

Syntheses and NMR spectroscopic investigations

Complex fac-[PtMe₃(Me₂CO)₃][BF₄] (3) reacted in anhydrous acetone with ligands of type 4 to give mononuclear complexes fac-[PtMe₃(ch-SEt)][BF₄] (36–40) in good yields of 62–87% (Scheme 5, Table 3), where the carbohydrate ligands could coordinate in a tridentate binding fashion. The colorless and beige powders are highly (36–38) and moderately (39, 40) air and moisture sensitive, respectively. All complexes were fully characterized by NMR (¹H, ¹³C, ¹⁹⁵Pt) spectroscopy, IR spectroscopy and high resolution mass spectroscopy.

Scheme 5.

Syntheses of carbohydrate platinum(IV) complexes fac-[PtMe₃(ch*)][BF₄] (ch* = ch-SEt, 36–40; ch-STaz, 41; ch-SPT, 42–44; ch-Sbpy, 45, 46). N_pic = picoline-2-yl.

Table 3.

¹H and ¹³C NMR spectroscopic data (δ in ppm, J in Hz) of the methyl ligands and ¹⁹⁵Pt chemical shifts of the complexes fac-[PtMe₃(ch*)][BF₄] (36–46)

Complex	ch*	δH	δC	2JPt,H	δPt
	ch-SEt
36	4a	1.28	−11.2	73.9	−2673
37	4c	1.26	−11.7	74.0a	−2442
38	4d	1.18a	−11.3	75.9	−2610
39	4e	1.06/1.12	−5.4/−8.6	69.8/72.8	−2068
40	4f	0.89/1.26/1.65	4.5/−1.3/−3.8	72.9/69.3/71.1	−2679
	ch-STaz
41	5h	0.81/1.31/1.75	0.2/−4.9/−8.1	73.0/71.4/70.5	−2377
	ch-SPT
42	6a	1.47	−5.8	br	−2154
43	6b	1.32	−5.9	br	−2158
44	6c	1.41	−5.7	br	−2151
	ch-Sbpy
45	7a	1.45b	−3.4	70.5b	−2123
46	7b	1.33	−3.5	br	−2120

^aAt −50 °C: 0.94/1.07/1.33 ppm (76.9/80.6/79.3 Hz).

^bAt −80 °C: 0.94/1.27/1.31 ppm (79.2/65.9/68.4 Hz).

In the ¹H NMR spectra of 36–38 the methyl ligands possessed broad mean signals in a range of 1.18–1.28 ppm flanked by platinum satellites. Chemical shifts and coupling constants are given in Table 3. Measurements at −50 °C using complex 38 as an example, showed the expected split into three separate, sharp signals, revealing the non-equivalence of the methyl ligands. For complexes 39 and 40 having protecting groups at C6 with additional N-donor sites (picoline-2-yl, bipyridine-6-yl), the ¹H NMR spectra showed two slightly broadened (39) and three separate sharp signals (40) for the methyl ligands, respectively, flanked by platinum satellites (Table 3). For the signals of the carbohydrate protons in the complexes 36–40, a broadening of all signals was found for 36–38. For complexes 39 and 40 only partial broadening was observed. The respective signals for the carbon atoms are partially broadened in all complexes 36–40. Coordination-induced shifts (Δδ_H/Δδ_C) for the methylene group resonances of the SEt moiety (0.16–0.52/0.5–3.2 ppm) and H1 (0.17–0.43/1.3–3.1 ppm) gave evidence that the sulfur atom is coordinated to the platinum atom. The two remaining coordination sites of the platinum atom in 36–38 are, most likely, occupied by any of the following: ring, ether or ester oxygen donor atoms of the carbohydrates. Thus, an κS,κ²O,O′ coordination mode of the carbohydrate ligands in complexes 36–38 can be assumed. In complexes 39 and 40, the coordination of the picoline-2-yl and bipyridine-6-yl moiety could be clearly seen by a significant downfield shift of the appropriate signals in ¹H and ¹³C NMR spectra up to 0.67 and 5.8 ppm, respectively. This corresponds to an κS,κN,κO (39) and κS,κ²N,N′ (40) coordination mode of the carbohydrate ligands.

Surprisingly, reactions of fac-[PtMe₃(Me₂CO)₃][BF₄] (3) with ligands of type 5 led to no isolable products. After adding a solution of 3 in acetone to the thioglycoside, in contrast to the common reactions, white precipitates were formed. ¹H NMR spectra of the reaction mixtures showed a multitude of products in the carbohydrate area, including the α-hemiacetal. This indicated that a cleavage of the C1–S bonds had occurred in a similar fashion to the decomposition reactions shown in Scheme 3.

To succeed in the formation of fac-[PtMe₃(ch-STaz)][BF₄] complexes, carbohydrate 5h having a stabilizing bipyridine-6-yl moiety at C6 (as in 4f) was selected. In the reaction of fac-[PtMe₃(Me₂CO)₃][BF₄] (3) with 5h the complex fac-[PtMe₃(ch-STaz)][BF₄] (41; ch-STaz = 5h) was isolated as a moderately air stable, yellow powder in a yield of 60%. ¹H and ¹³C NMR spectra showed unambiguously the coordination of the bipyridine-6-yl moiety with chemical shift differences of the bipyridine resonances shifted downfield up to 0.92 ppm and 7.1 ppm, respectively. Furthermore, remarkable CIS’s of the signals of H1 and C1, which amount to 0.23 (¹H NMR) and 4.9 ppm (¹³C NMR), respectively, are observed. The identity of 41 was also confirmed by high resolution mass spectrometry (Fig. 6). The isotopic pattern of the molecular cation is in a very good agreement with the calculated values.

Fig. 6.

Isotopic pattern of the cation fac-[PtMe₃(5h)]⁺ of complex 41 at 945.2684 m/z, showing the expected intensity due to the isotopic composition given by horizontal bars.

Obviously, carbohydrates possessing chelating donor groups are the key to yield stable fac-[PtMe₃(ch*)][BF₄] complexes. Therefore, the carbohydrate classes ch-SPT (type 6, Scheme 1) and ch-Sbpy (type 7, Scheme 1), having a chelating group in the aglycone moiety, were included in the subsequent investigations. Reactions of fac-[PtMe₃(Me₂CO)₃][BF₄] (3) with ligands of type 6 and 7 led to the formation of complexes 42–46, which were isolated as yellow and beige powders, respectively, in yields of 54–75% (Scheme 5). These complexes are stable in anhydrous acetone solutions over a few weeks, without any evidence of decomposition. In chloroform, however, decomposition was observed within 4 days, which might be caused by the presence of traces of hydrochloric acid. The identities of the complexes were confirmed by ¹H, ¹³C and ¹⁹⁵Pt NMR spectroscopy, IR spectroscopy and high resolution ESI mass spectrometry.

The methyl ligands gave broad mean signals in the ¹H NMR spectra at 1.32–1.47 ppm, flanked by platinum satellites (Table 3). ¹H NMR experiments performed at −80 °C with complex 45 as an example showed the expected split into three separate signals due to the non-equivalence of the methyl ligands. The SPT and Sbpy moieties were unambiguously found to be coordinated to the platinum atom. This was verified by remarkable downfield shifts of the related signals of the protons and carbon atoms up to 1.0 ppm (¹H NMR) and 5.1 ppm (¹³C NMR). The carbohydrate proton resonances are shifted up to 0.41 ppm and are partially broadened, whereas the ¹³C NMR spectra of compounds 45 and 46 only showed a significant shift of 2.4 (45) and 2.9 (46) ppm for the signals of C1. Also, a broadening of the resonances of C1 and C2 (42–46) and C4 (44) can be observed. This indicates that the exocyclic sulfur of the SPT and Sbpy moieties might be the third donor atom coordinated to the platinum atom.

The ESI mass spectra for complexes 42–46 showed the presence of a mononuclear cation fac-[PtMe₃(ch*)]⁺ (ch* = ch-SPT, 42–44; ch-Sbpy, 45, 46) containing one platinum atom. The full scan mass spectrum of 43, depicted in Fig. 7, shows no other platinum-containing cations. The isotopic pattern of the fac-[PtMe₃(ch-SPT)]⁺ (ch-SPT = 6b) cation at 1012.1890 m/z is in very good agreement with the calculated values.

Fig. 7.

(a) Positive ESI-mass spectrum of the cation fac-[PtMe₃(6b)]⁺ of complex 43. (b) Isotopic pattern of the molecular ion fac-[PtMe₃(6b)]⁺ at 1012.1890 m/z showing the expected intensity due to the isotopic composition given by horizontal bars.

3. Conclusion

Platinum(IV) complexes with thioglycoside ligands of the types fac-[PtMe₃(4,4′-R₂bpy)(ch*)][BF₄] (ch* = ch-SEt, 8–14; ch-STaz, 15–23), fac-[PtMe₃(OAc-κ²O,O′)(ch*)] (ch* = ch-SEt, 24–28; ch-STaz, 29–35) and fac-[PtMe₃(ch*)][BF₄] (ch* = ch-SEt, 36–40; ch-STaz, 41; ch-SPT, 42–44; ch-Sbpy, 45, 46), with the thioglycosides coordinated in a mono- (8–35) and tridentate (36–46) binding fashion have been synthesized. Despite the kinetic inertness of platinum(IV) complexes due to their low spin d⁶ electron configuration, it could be shown that in trimethylplatinum(IV) complexes weakly coordinating ligands like acetone could be smoothly substituted by thioglycosides. These ligand exchange reactions are further supported by the high trans effect of the methyl ligands. Furthermore, platinum mediated decomposition of thioglycosides in complexes 21 and 23 involving the cleavage of the C–S glycosidic bonds, yielded the corresponding products 21a and 23a (Scheme 3). This result is in accordance with common glycosylation procedures, wherein the glycosidic bond of the glycosyl donor is activated in the first step by adding an electrophilic promoter, such as MeOTf or NIS/TfOH.²

As expected from the coordination chemistry perspective, complexes of platinum(IV) in which the thioglycoside ligands have three coordination sites at their disposal (i.e. using fac-[PtMe₃(Me₂CO)₃][BF₄] (3) as starting complex) proved to be more air and moisture sensitive than the cationic complexes with bipyridine and the neutral complexes with acetato ligands. Thus, complexes with thioglycoside ligands having only the SEt group as strong donor site could be prepared and characterized (36–38), whereas it was not possible with complexes having only the STaz group as the strongest donor site. In the latter cases, a partial cleavage of the glycosidic bonds instead of the anticipated complex formation took place. These cleavage reactions are promoted by the STaz coordination to Pt, as discussed before being a further example for the cleavage of glycosidic bonds by electrophilic promoters.² However, it can’t be strictly ruled out that these reactions are also influenced by traces of water and/or Ag[BF]₄ (present in the reaction mixtures despite using strictly anaerobic conditions and from the in situ synthesis of complex 3, respectively).^23,24 Analogous platinum-mediated reactions, such as cleavage and formation of isopropylidene protecting groups and Schiff bases, were frequently observed in carbohydrate trimethylplatinum(IV) complexes, with non-functionalized carbohydrate ligands.^12,13 In full accord with these findings, we succeeded to get stable complexes of the type fac-[PtMe₃(ch-STaz)][BF₄] with a derivative having additional strong donor sites in form of a 2,2′-bipyridine-6-yl protecting group at C6 of the carbohydrate moiety (41).

For the first time the investigations presented in this study give a deeper insight into the coordination chemistry of thioglycosides to platinum(IV) being a coordination center in a relatively high oxidation number. It has been shown that these ligands can be coordinated not only monodentately through a relatively strong donor site (κS or κN) but also facial tridentately using donor sets consisting of one stronger and two weaker donor sites (κS,κ²O,O′; O = oxygen atom from the carbohydrate backbone), two stronger and one weaker donor sites (κS,κN,κO) or three stronger donor sites (κS,κ²N,N′ or κ³N,N′,N″). Furthermore, coordination of thioglycosides to the highly electrophilic platinum center may give rise to platinum-assisted cleavage of glycosidic C–S bonds, which creates a basis to a deeper understanding of stereocontrolled chemical glycosylations, mediated by metal coordination.¹⁴

4. Experimental

4.1. General considerations

General considerations

Syntheses were performed, in general, under strictly dehydrated conditions in an argon atmosphere using standard Schlenk techniques. As precipitates, the carbohydrate platinum complexes are stable for a few hours (2–4 h) even in open air, whereas a strictly anhydrous environment was required for handling their solutions in acetone. Acetone and pentane were dried over phosphorus pentoxide followed by 4 Å molecular sieves and LiAlH₄, respectively. Diethyl ether was dried over Nabenzophenone. All solvents were distilled prior to use. NMR spectra were obtained with Varian UNITY 500, Gemini 2000 and Bruker 800 spectrometers using solvent signals (¹H and ¹³C NMR spectroscopy) as internal references and Na₂[PtCl₆] (δ(¹⁹⁵Pt) = 0 ppm) as external reference. IR spectra were recorded on a Galaxy Mattson FT IR spectrometer, using KBr pellets. The positive ion high resolution ESI mass spectra were obtained from a Bruker Apex III Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer (Bruker Daltonics, Billerica, USA) equipped with an Infinity cell, a 7.0 Tesla superconducting magnet (Bruker), a RF-only hexapole ion guide and an external electron spray ion source (Agilent, off axis spray, voltages: endplate, −3.700 V; capillary, −4.200 V; capillary exit, 100 V; skimmer 1, 15.0 V; skimmer 2, 6.0 V). Nitrogen was used as drying gas at 150 °C. The sample solutions were introduced continuously via a syringe pump with a flow rate of 120 µl h⁻¹. The data were acquired with 512 k data points and zero filled to 2048 k by averaging 64 scans. fac-[(PtMe₃I)₄]^14,25 and fac-[PtMe₃I(bpy)]²⁰ were prepared according to literature methods. All other materials were purchased from commercial sources. Synthesis of fac-[PtMe₃I(4,4′-^tBu₂bpy)] and its analytical data as well as the NMR and IR spectroscopic data of the carbohydrate platinum complexes 1–46 are available as ESI.^† Selected spectroscopic data of complexes 1–46 are given in Table 1–3.

General method for the synthesis of the complexes fac-[PtMe₃(4,4′-R₂bpy)(ch*)][BF₄](ch* = ch-SEt, R = H: 8–12; R = ^tBu: 13, 14; ch-STaz, R = H: 17–23, R = ^tBu: 15, 16)

A suspension of fac-[PtMe₃I(bpy)] (70.0 mg, 0.14 mmol) or fac-[PtMe₃I(4,4′-^tBu₂bpy)] (88.9 mg, 0.14 mmol) and Ag[BF₄] (26.5 mg, 0.14 mmol) in acetone (10 ml) was stirred for 30 min under the absence of light. Precipitated AgI was removed by filtration and the clear, colorless solution of fac-[PtMe₃(Me₂CO)(4,4′-R₂bpy)][BF₄] (R = H, 1a; R = ^tBu, 1b) was added to the respective β-d-thiopyranoside (0.14 mmol). After 5 h the volume of the solution was reduced in vacuo to 3 ml and pentane (10 ml) was added. The precipitated solid was filtered, washed with pentane (2 × 2 ml) and dried in vacuo.

• fac-[PtMe₃(bpy)(ch-SEt)][BF₄] (8, ch-SEt = 4a). (88 mg, 72%); m/z (ESI) 788.2192 ([PtMe₃(bpy)(4a)]⁺. C₂₉H₄₁N₂O₉PtS requires 788.2181).

• fac-[PtMe₃(bpy)(ch-SEt)][BF₄] (9, ch-SEt = 4b). (115 mg, 73%); m/z (ESI) 788.2193 ([PtMe₃(bpy)(4b)]⁺. C₂₉H₄₁N₂O₉PtS requires 788.2181).

• fac-[PtMe₃(bpy)(ch-SEt)][BF₄] (10, ch-SEt = 4c). (102 mg, 65%); m/z (ESI) 1036.2805 ([PtMe₃(bpy)(4c)]⁺. C₄₉H₄₉N₂O₉PtS requires 1036.2807).

• fac-[PtMe₃(bpy)(ch-SEt)][BF₄] (11, ch-SEt = 4d). (107 mg, 78%); m/z (ESI) 980.3623 ([PtMe₃(bpy)(4d)]⁺. C₄₉H₄₉N₂O₉PtS requires 980.3636).

• fac-[PtMe₃(bpy)(ch-SEt)][BF₄] (12, ch-SEt = 4e). (90 mg, 68%); m/z (ESI) 981.3586 ([PtMe₃(bpy)(4e)]⁺. C₄₈H₅₆N₃O₅PtS requires 981.3588).

• fac-[PtMe₃(4,4′-^tBu₂bpy)(ch-SEt)][BF₄] (13, ch-SEt = 4a). (82 mg, 65%); m/z (ESI) 900.3437 ([PtMe₃(4,4′-^tBu₂bpy)(4a)]⁺. C₃₇H₅₇N₂O₉PtS requires 900.3432).

• fac-[PtMe₃(4,4′-^tBu₂bpy)(ch-SEt)][BF₄] (14, ch-SEt = 4c). (72 mg, 54%); m/z (ESI) 1148.4030 ([PtMe₃(4,4′-^tBu₂bpy)(6c)]⁺. C₃₇H₅₇N₂O₉PtS requires 1148.4058).

• fac-[PtMe₃(4,4′-^tBu₂bpy)(ch-STaz)][BF₄] (15, ch-STaz = 5c). (82 mg, 45%); m/z (ESI) 1205.3743 ([PtMe₃(5c)(4,4′-^tBu₂bpy]⁺. C₅₈H₆₄N₃O₉PtS₂ requires 1205.3732).

• fac-[PtMe₃(4,4′-^tBu₂bpy)(ch-STaz)][BF₄] (16, ch-STaz = 5g). (108 mg, 76%); m/z (ESI) 1101.3480 ([PtMe₃(4,4′-^tBu₂bpy)(5g)]⁺. C₅₈H₆₄N₃O₉PtS₂ requires 1101.3470).

• fac-[PtMe₃(bpy)(ch-STaz)][BF₄] (17, ch-STaz = 5a). (130 mg, 85%); m/z (ESI) 845.1841 ([PtMe₃(bpy)(5a)]⁺. C₃₀H₄₀N₃O₉PtS₂ requires 845.1854).

• fac-[PtMe₃(bpy)(ch-STaz)][BF₄] (18, ch-STaz = 5b). (76 mg, 64%); m/z (ESI) 1093.2478 ([PtMe₃(bpy)(5b)]⁺. C₅₀H₄₈N₃O₉PtS₂ requires 1083.2480).

• fac-[PtMe₃(bpy)(ch-STaz)][BF₄] (19, ch-STaz = 5c). (115 mg, 73%); m/z (ESI) 1093.2479 ([PtMe₃(bpy)(5c)]⁺. C₅₀H₄₈N₃O₉PtS₂ requires 1093.2480).

• fac-[PtMe₃(bpy)(ch-STaz)][BF₄] (20, ch-STaz = 5d). (72 mg, 72%); m/z (ESI) 1037.3305 ([PtMe₃(bpy)(5d)]⁺. C₅₀H₄₈N₃O₉PtS₂ requires 1037.3309).

• fac-[PtMe₃(bpy)(ch-STaz)][BF₄] (21, ch-STaz = 5e). (91 mg, 83%); m/z (ESI) 733.2074 ([PtMe₃(bpy)(5e)]⁺. C₂₆H₄₀N₃O₅PtS₂ requires 733.2057).

• fac-[PtMe₃(bpy)(ch-STaz)][BF₄] (22, ch-STaz = 5f). (112 mg, 94%); m/z (ESI-MS) 893.2203 ([PtMe₃(bpy)(5f)]⁺. C₃₅H₄₄N₃O₈PtS₂ requires 893.2218).

• fac-[PtMe₃(bpy)(ch-STaz)][BF₄] (23, ch-STaz = 5g). (91 mg, 83%); m/z 989.2243 (ESI) ([PtMe₃(bpy)(5g)]⁺. C₄₃H₄₄N₃O₈PtS₂ requires 989.2218).

General method for the synthesis of the complexes [PtMe₃(OAc-κ²O, O′)(ch*)] (ch* = ch-SEt, 24–28; ch-STaz, 29–35)

A suspension of fac-[(PtMe₃I)₄] (50.0 mg, 0.04 mmol) and AgOAc (23.0 mg, 0.14 mmol) in acetone (10 ml) was stirred for 12 h under the absence of light. Precipitated AgI was removed by filtration and the clear, colorless solution of fac-[PtMe₃(OAc-κ²O,O′)(Me₂-CO)] (2) was directly added to the respective β-d-thiopyranoside (0.14 mmol). After 5 h the volume of the solution was reduced in vacuo to 3 ml and pentane (6 ml) was added. The precipitated solid was filtered, washed with pentane (2 × 2 ml) and dried in vacuo.

• fac-[PtMe₃(OAc-κ²O,O′)(ch-SEt)] (24, ch-SEt = 4a). (55 mg, 57%); m/z (ESI) 632.1498 ([PtMe₃(OAc-κ²O,O′)(4a)]⁺_−OAc. C₃₀H₄₀N₃O₉PtS₂ requires 632.1493).

• fac-[PtMe₃(OAc-κ²O,O′)(ch-SEt)] (25, ch-SEt = 4b). (62 mg, 70%); m/z (ESI) 632.1498 [PtMe₃(OAc-κ²O,O′)(4b)]⁺_−OAc. C₃₀H₄₀N₃O₉PtS₂ requires 632.1493).

• fac-[PtMe₃(OAc-κ²O,O′)(ch-SEt)] (26, ch-SEt = 4c). (64 mg, 54%); m/z (ESI) 880.2108 ([PtMe₃(OAc-κO,O′)(4c)]⁺_−OAc. C₃₀H₄₀N₃O₉PtS₂ requires 880.2119).

• fac-[PtMe₃(OAc-κ²O,O′)(ch-SEt)] (27, ch-SEt = 4d). (64 mg, 54%); m/z 824.2939 ([PtMe₃(OAc-κ²O,O′)(4d)]⁺_−OAc. C₃₉H₄₉O₅PtS requires 824.2948).

• fac-[PtMe₃(OAc-κ²O,O′)(ch-SEt)] (28, ch-SEt = 4e). (75 mg, 58%); m/z (ESI) 825.2871 ([PtMe₃(OAc-κ²O,O′)(4e)]⁺_−OAc. C₃₈H₄₈NO₅PtS requires 825.2901).

• fac-[PtMe₃(OAc-κ²O,O′)(ch-STaz)] (29, ch-STaz = 5a). (93 mg, 89%); m/z (ESI) 689.1172 ([PtMe₃(OAc-κ²O,O′)(5a)]⁺_−OAc. C₂₀H₃₂NO₉PtS₂ requires 689.1166).

• fac-[PtMe₃(OAc-κ²O,O′)(ch-STaz)] (30, ch-STaz = 5b). (120 mg, 86%); m/z (ESI) 937.1753 ([PtMe₃(OAc-κ²O,O′)(5b)]⁺_−OAc. C₄₀H₄₀NO₉PtS₂ requires 937.1792).

• fac-[PtMe₃(OAc-κ²O,O′)(ch-STaz)] (31, ch-STaz = 5c). (86 mg, 68%); m/z (ESI) 937.1789 ([PtMe₃(OAc-κ²O,O′)(4e)]⁺_−OAc. C₁₆H₃₂NO₅PtS₂ requires 937.1792).

• fac-[PtMe₃(OAc-κ²O,O′)(ch-STaz)] (32, ch-STaz = 5d). (102 mg, 80%); m/z (ESI) 881.2630 ([PtMe₃(OAc-κ²O,O′)(5d)]⁺_−OAc. C₄₀H₄₈NO₅PtS₂ requires 881.2622).

• fac-[PtMe₃(OAc-κ²O,O′)(ch-STaz)] (33, ch-STaz = 5e). (30 mg, 35%); m/z (ESI) 577.1368 [PtMe₃(OAc-κ²O,O′)(5e)]⁺_−OAc. C₁₆H₃₂NO₅PtS₂ requires 577.1370).

• fac-[PtMe₃(OAc-κ²O,O′)(ch-STaz)] (34, ch-STaz = 5f). (67 mg, 60%); m/z (ESI) 737.1525 ([PtMe₃(OAc-κ²O,O′)(5f)]⁺_−OAc. C₂₅H₃₆NO₈PtS₂ requires 737.1530).

• fac-[PtMe₃(OAc-κ²O,O′)(ch-STaz)] (35, ch-STaz = 5g). (44 mg, 35%); m/z (ESI) 833.1553 ([PtMe₃(OAc-κ²O,O′)(5g)]⁺_−OAc. C₃₃H₃₆NO₈PtS₂ requires 833.1530).

General method for the synthesis of the complexes [PtMe₃(ch*)]-[BF₄] (ch* = ch-SEt, 36–40; ch-STaz, 41, ch-SPT, 42–44, ch-Sbpy, 45, 46)

A suspension of fac-[(PtMe₃I)₄] (70.0 mg, 0.04 mmol) and Ag[BF₄] (26.5 mg, 0.14 mmol) in acetone (10 ml) was stirred for 30 min under the absence of light. Precipitated AgI was removed by filtration and the clear, colorless solution of fac-[PtMe₃(Me₂CO)₃][BF₄] (3) was directly added to the respective β-d-thiopyranoside (0.14 mmol). After 5 h the volume of the solution was reduced in vacuo to 3 ml and pentane (10 ml) was added. The precipitated solid was filtered, washed with pentane (2 × 2 ml) and dried in vacuo.

• fac-[PtMe₃(ch-SEt)][BF₄] (36, ch-SEt = 4a). (42 mg, 87%); m/z (ESI) 632.1492 [PtMe₃(4a)]⁺. C₁₉H₃₃O₉PtS requires 632.1493).

• fac-[PtMe₃(ch-SEt)][BF₄] (37, ch-SEt = 4c). (40 mg, 62%); m/z (ESI) 880.2115 ([PtMe₃(4c)]⁺. C₃₉H₄₁O₉PtS requires 880.2119).

• fac-[PtMe₃(ch-SEt)][BF₄] (38, ch-SEt = 4d). (53 mg, 70%); m/z (ESI) 824.2948 ([PtMe₃(4d)]⁺. C₃₉H₄₉O₅PtS requires 824.2948).

• fac-[PtMe₃(ch-SEt)][BF₄] (39, ch-SEt = 4e). (92 mg, 72%); m/z (ESI) 825.2903 ([PtMe₃(4e)]⁺. C₃₈H₄₈NO₅PtS requires 825.2901).

• fac-[PtMe₃(ch-SEt)][BF₄] (40, ch-SEt = 4f). (118 mg, 85%); m/z (ESI) 888.2940 ([PtMe₃(4f)]⁺. C₄₃H₄₈N₃O₅PtS₂ requires 888.3010).

• fac-[PtMe₃(ch-STaz)][BF₄] (41, ch-STaz = 5h). (87 mg, 60%); m/z (ESI) 945.2684 ([PtMe₃(5h)]⁺. C₄₃H₄₈N₃O₅PtS₂ requires 945.2683).

• fac-[PtMe₃(ch-SPT)][BF₄] (42, ch-SPT = 6a). (77 mg, 65%); m/z (ESI) 764.1262 ([PtMe₃(6a)]⁺. C₂₅H₃₃N₂O₉PtS₂ requires 764.1275).

• fac-[PtMe₃(ch-SPT)][BF₄] (43, ch-SPT = 6b). (83 mg, 54%); m/z (ESI) 1012.1890 ([PtMe₃(6b)]⁺. C₄₅H₄₁N₂O₉PtS₂ requires 1012.1901).

• fac-[PtMe₃(ch-SPT)][BF₄] (44, ch-SPT = 6c). (98 mg, 67%); m/z (ESI) 956.2702 ([PtMe₃(6c)]⁺. C₄₅H₄₉N₂O₅PtS₂ requires 956.2731).

• fac-[PtMe₃(ch-Sbpy)][BF₄] (45, ch-Sbpy = 7a). (89 mg, 75%); m/z (ESI) 758.1679 ([PtMe₃(7a)]⁺. C₂₇H₃₅N₂O₉PtS requires 758.1711).

• fac-[PtMe₃(ch-Sbpy)][BF₄] (46, ch-Sbpy = 7b). (101 mg, 66%); m/z (ESI) 1006.2331 ([PtMe₃(7b)]⁺. C₄₇H₄₃N₂O₉PtS requires 1006.2337).

4.2. X-Ray crystallography^†

Single crystals of fac-[PtMe₃(bpy)(ch-STaz-κN)][BF₄] (ch-STaz = 5c, 19), fac-[PtMe₃(bpy)(STazH-κS)][BF₄] (21a) and 1,6-anhydro-2,3,4-tri-O-benzoyl-glucopyranose (23a) for X-ray diffraction measurements were obtained from acetone/ether/THF (1 : 1 : 1) (19) and acetone/ether/pentane solutions (1 : 1 : 1) (21a, 23a), respectively. Intensity data were collected on a Oxford Gemini S diffractometer with Cu-Kα radiation (λ = 1.54184 Å, graphite monochromator) at 100(2) K (19) and on a Bruker Apex II Kappa diffractometer with Mo-Kα radiation (λ = 0.71073 Å, graphite monochromator) at 100(2) K (21a, 23a). A summary of the crystallographic data, the data collection parameters and the refinement parameters is given in Table 4. Numerical (21a) and multiscan (23a) absorption corrections were applied (T_min/T_max 0.18/0.55, 21a; T_min/T_max 0.97/0.98, 23a). The structures were solved by direct methods with SHELXS-97²⁶ and refined using full matrix least square routines against F² with SHELXL-97.²⁶ Non-hydrogen atoms were refined with anisotropic displacement parameters. The hydrogen atom attached to nitrogen in 21a was found in the difference Fourier map and refined freely. All other hydrogen atoms were positioned geometrically and refined with isotropic displacement parameters according to the “riding model”. Although measured at 100 K with Cu-Kα radiation the small sized needle-like crystals (0.3 × 0.03 × 0.03 mm) of complex 19 showed only a weak reflectivity resulting in a limited quality of the structure solution. The required fixing of disordered groups (phenyl rings and [BF₄]⁻ anions) for the refinement of 19, led to the comparatively high number of restraints. The fluoroatom F4 of the tetrafluoroborate anion in complex 21a was found to be disordered over two equally occupied positions.

Table 4.

Crystal data, data collection and refinement parameters of fac-[PtMe₃(bpy)(ch-STaz-κN)][BF₄] (19, ch-STaz = 5c), fac-[PtMe₃(bpy)(STazH-κS)][ BF₄] (21a) and 1,6-anhydro-2,3,4-tri-O-benzoyl-β-d-glucopyranose (23a)

	19	21a	23a
Formula	C50H48BF4N3O9PtS2	C16H22BF4N3PtS2	C27H22O8
FW	1180.94	602.39	474.45
Crystal system	Tetragonal	Monoclinic	Triclinic
Space group	P41212	P21/c	P1
a/Å	22.1611(9)	13.2216(5)	9.6936(8)
b/Å	22.1611(9)	12.6149(5)	11.011(1)
c/Å	43.735(2)	12.8474(5)	11.449(1)
α/°			66.414(4)
β/°		115.776(2)	89.999(4)
γ/°			89.894(4)
V/Å 3	21479(2)	1929.6(1)	1119.9(2)
Z	16	4	2
Dcalc./g cm−3	1.461	2.074	1.407
T/K	100(2)	100(2)	100(2)
µ/mm−1	6.194	7.532	0.104
θ/°	4.47–61.49	1.71–36.00	1.94–26.44
F(000)	9472	1160	496
Index ranges	−23 ≤ h ≤ 20	−21 ≤ h ≤ 21	−11 ≤ h ≤ 12
	−25 ≤ k ≤ 25	−19 ≤ k ≤ 20	−13 ≤ k ≤ 13
	−49 ≤ l ≤ 47	−21 ≤ l ≤ 21	−14 ≤ l ≤ 14
Reflns collected	66857	56461	28835
Reflns obs [I > 2σ(I)]	4582	7098	6186
Reflns independent	16385 (Rint = 0.1328)	9070 (Rint = 0.0643)	8089 (Rint = 0.0699)
Data/restraints/parameters	16385/1332/1103	9070/1/257	8089/3/604
GOF(F2)	0.617	1.034	1.003
R1, wR2 (I > 2 σ)	0.0481/0.0785	0.0347/0.0757	0.0602/0.1447
R1, wR2 (all data)	0.1755/0.0966	0.0529/0.0828	0.0810/0.1593
Largest diff. peak and hole/e Å −3	1.009 and −0.519	1.958 and −1.058	0.358 and −0.350
Flack parameter	−0.044(9)		0.4(10)

4.3. Computational details

DFT calculations of compounds were carried out by the Gaussian 03 program package²⁷ using the hybrid functional B3LYP.²⁸ The 6-311G(d,p) basis sets as implemented in Gaussian 03 were employed for main group atoms. The valence shell of platinum has been approximated by a split valence basis set too; for its core orbitals an effective core potential in combination with consideration of relativistic effects has been used.²⁹ The appropriateness of the functional in combination with the basis sets and effective core potential used for reliable interpretation of structural and energetic aspects of related platinum complexes has been demonstrated.³⁰ All systems were fully optimized without any symmetry restrictions. The resulting geometries were characterized as equilibrium structures by the analysis of the force constants of normal vibrations. Solvent effects were considered according to the polarized continuum model as implemented in Gaussian 03.³¹