Mono- and Binuclear Copper(I) Complexes of Thionucleotide Analogues and Their Catalytic Activity on the Synthesis of Dihydrofurans

Abstract

The reaction of copper(I) halides with 2-thiouracil (TUC), 6-methyl-2-thiouacil (MTUC), and 4-methyl-2-mercaptopyrimidine (MPMTH) in the presence of triphenylphosphine (tpp) in a 1:1:2 molar ratio results in a mixed-ligand copper(I) complex with the formulas [Cu2(tpp)4(TUC)Cl] (1), [Cu2(tpp)4(MTUC)Cl] (2), [Cu(tpp)2(MPMTH)Cl]·(1)/2CH3OH (3), [Cu(tpp)2(MTUC)Br] (4), and [Cu(tpp)2(MTUC)I]·(1)/2CH3CN (5). The complexes have been characterized by FT-IR, (1)H NMR, and UV-vis spectroscopic techniques and single-crystal X-ray crystallography. Complexes 1 and 2 are binuclear copper(I) complexes. Two phosphorus atoms from tpp ligands are coordinated to the copper(I) ions, forming two units that are linked to each other by a deprotonated TUC or MTUC chelating ligand through a sulfur bridge. A linear Cu-S-Cu moiety is formed. The tetrahedral geometry around the metal centers is completed by the nitrogen-donor atom from the TUC or MTUC ligand for the one unit, while for the other one, it is completed by the chloride anion. Two phosphorus atoms from two tpp ligands, one sulfur atom from MPMTH or MTUC ligand, and one halide anion (Cl, Br, and I) form a tetrahedron around the copper ion in 3-5 and two polymorphic forms of 4 (4a and 4b). In all of the complexes, either mono- or binuclear intramolecular O-H···X hydrogen bonds enhance the stability of the structures. On the other hand, in almost all cases of mononuclear complexes (with the exception of a symmetry-independent molecule in 4a), intermolecular NH···O hydrogen-bonding interactions lead to dimerization. Complexes 1-5 were studied for their catalytic activity for the intermolecular cycloaddition of iodonium ylides toward dihydrofuran formation by HPLC, (1)H NMR, and LC-HRMS spectroscopic techniques. The results show that the geometry and halogen and ligand types have a strong effect on the catalytic properties of the complexes. The highest yield of dihydrofurans was obtained when "linear" complexes 1 and 2 were used as the catalysts. The activity of the metal complexes on the copper(I)-catalyzed and uncatalyzed intramolecular cycloaddition of iodonium ylide is rationalized through electronic structure calculation methods, and the results are compared with the experimental ones.

Synthesis, Structural Studies, and Anticancer Properties of [CuBr(PPh3)2(4,6-Dimethyl-2-Thiopyrimidine-κS]

“…For the title compound, τ 4 = 0.93 is slightly higher than the τ 4 = 0.90 of the [CuBr(PPh 3 ) 3 ] complex, which means that the overall tetrahedral character around the Cu-atom was not substantially altered by the substitution of the PPh 3 group by the -thione ligand. In general, all the interatomic distances are comparable to the corresponding distances reported in identical Cu-complexes [14,28,[48][49][50]52]. In the title compound, the Cu-Br distance (2.5412(2) Å) is slightly longer, while the Cu-P average distance of 2.275 Å became shorter compared to the respective distances (2.497(1) Å and 2.333 Å) observed in the parent compound, which is related to the thione-S donor substitution in the title compound.…”

“…shows the molecular structure of [CuBr(PPh3)2(C6H8N2S)]. The geomet rical feature of the molecule resembles the parent [CuBr(PPh3)3] complex and other simila Cu(I) halide complexes with CuXSP2 cores[14,28,[48][49][50]. The heavily distorted tetrahedra coordination of the copper compound is realized by the S-atom of the -thione, the P-atom of phosphine, and bromo ligands.…”

New Apoptosis Inducers Containing Anti-inflammatory Drugs and Pnictogen Derivatives: A New Strategy in the Development of Mitochondrial Targeting Chemotherapeutics

“…The resonance signals at 7.899–7.873 ppm (d) (H­[C 3 ]), 7.328–7.286 ppm (t) (H­[C 6 ]), 7.140–7.096 ppm (m) (H­[C 4 ]), 7.050–7.008 ppm (m) (H­[C 5 ], H­[C 5′ ], H­[C 4′ ]), and 6.711–6.674 (t) ppm (H­[C 6′ ]) (Chart ) are attributed to the aromatic H located in mefH (Figures S9–S12). Moreover, the 1 H NMR spectra of the pnictogen derivatives tpE are dominated by the presence of two multiplet signals that are attributed to the phenyl at 7.376–7.354 ppm (t) (H­[C a ]) and 7.239–7.171 ppm (m) (H­[C c ] and H­[C d ]) (tpP), , 7.366–7.341 ppm (t) (H­[C a ]) and 7.260–7.221 ppm (m) (H­[C c ] and H­[C d ]) (tpAs), , and 7.394–7.312 ppm (m) (H­[C a ], H­[C c ], and H­[C d ]) (tpSb) (Chart ). These signals are observed at 7.957–7.933 ppm (H­[C 3 ]), 7.153–7.110 ppm (H­[C 6 ]), 7.053–7.014 ppm (H­[C 4 ], 6.863–6.836 ppm (H­[C 5 ], H­[C 5′ ], H­[C 4′ ]), and 6.635–6.596 ppm (H­[C 6′ ]) in the spectrum of 1 (Figure S9).…”

Ruthenium(II) complexes with 6-methyl-2-thiouracil selectively reduce cell proliferation, cause DNA double-strand break and trigger caspase-mediated apoptosis through JNK/p38 pathways in human acute promyelocytic leukemia cells

“…The antineoplastic potential of the metal-based complexes dependent on the nature of the ligands, and metallodrugs complexes containing nucleobases and their derivatives have been previously explored. These include ruthenium(II) complexes with thymine and 5-fluorouracil 9,11 ; palladium(II) complexes with 2-thiouracil ligands 17 ; gold(I) complexes with 2-thiouracil, 2-thiocytosine and 2-mercaptopyridine 18 ; and copper(I) complexes with 2-thiouracil, 6-methyl-2-thiouacil and 4-methyl-2-mercaptopyrimidine 19 . Recently, we synthesized four ruthenium(II) complexes with thiouracil derivatives using [RuCl 2 (PPh 3 ) 3 ] and [RuCl 2 (PPh 3 ) 2 (dppb)] complexes as precursors.…”