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-kappa2O,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-kappa2O,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-beta-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-kappaS)][BF4] (21a) and 1,6-anhydro-2,3,4-tri-O-benzoyl-beta-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 kappaS,kappa2O,O, kappaS,kappaN,kappaO and kappaS,kappa2N,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-beta-D-glucopyranoside (5h) resulting in fac-[PtMe3(ch-STaz)][BF4] (41, ch-STaz = 5h), having a kappa3N,N',N''coordinated thioglycoside ligand.

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.

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.

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.

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.

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.

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.

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.

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).

Scheme 3

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

Scheme 4

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

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.