Simultaneous N7,O6-Binding of Guanine to Two Zinc Centers and Its Possible Biological Significance

The reaction of ZnCl2 with 9-ethylguanine (9-EtGH) produced a novel dinuclear Zn(II) complex, [Zn2Cl4(H2O)(μ-9-EtGH-N7,O6)(9-EtGH-N7), 1. The X-ray structure analysis (monoclinic, P21 (No. 4), a = 11.0636(6) Å, b = 6.6546(4) Å, c = 15.9630(9) Å, β = 101.069(1)°, V = 1153.4(1) Å3, Z = 2) revealed that one of the tetrahedrally coordinated Zn(II) atoms binds to the N7 site of 9-EtGH and to the exocyclic O6 atom of another 9-EtGH molecule. The remaining Zn(II) atom binds to the N7 site of the second 9-EtGH moiety

Inversion of the Cis Geometry Requirement for Cytotoxicity in Structurally Novel Platinum(II) Complexes Containing the Bidentate N,O-Donor Pyridin-2-yl-acetate

Water soluble platinum(II) complexes have been synthesized that contain the N,O-chelate pyridin-2-yl acetate (PyAc) as a novel structural motif in platinum antitumor complexes. The trans-platinum complex trans-[PtCl(PyAc-N,O)(NH3)] (2) (N-donors are trans) and its isomer cis-[PtCl(PyAc-N,O)(NH3)] (4) (N trans to Cl) were prepared from trans-[PtCl2((NH3)(PyAcH)]·H2O (1·H2O) and cis-[PtCl2(NH3)(PyAcMe) (3), respectively, employing the bidentate ligand as its methylester (PyAcMe). 2 and 4 are readily formed from the respective dichloro species, even at low pH and in the presence of extra chloride, indicating a high thermodynamic stability of the PyAc chelate ring. 1·H2O and 2−4 were characterized by 1H NMR and IR spectroscopy and elemental analyses. The solid-state structure of 2 was determined:  triclinic, P1̄ (no. 2), with a = 8.170(2) Å, b = 9.274(3) Å, c = 7.374(2) Å, α = 108.68(2)°, β = 113.27(2)°, γ = 74.40(2)°, V = 479.7(6) Å3, Z = 2. The six-membered metallacyclus in 2 adopts a “boat” form, allowing a strainless coordination of platinum. The most promising cytotoxic properties in the above series of compounds have been established for 2 (and 1, which rapidly transforms into 2 at 37 °C and neutral pH). Preliminary ID50 values were 0.88 and 1.26 μM, respectively, in cisplatin-sensitive L1210 leukemia. Both compounds proved to be cross-resistant to the clinical drug. Reactions of 2 and 4 with 5‘-guanosine monophosphate (5‘-GMP) under physiological conditions gave the monofunctional adducts trans- and cis-[Pt(5‘-GMP-N7)(PyAc-N,O)(NH3)] (I and II). Chelate-bound carboxylate was not replaced by guanine-N7 when an excess of nucleotide was applied (NMR). In an analogous reaction, 2 reacts with the oligonucleotide d(TCGT) [5‘-T(1)-C(2)-G(3)-T(4)-3‘] to give the adduct d(TCGT)-N7(3)-Pt(PyAc-O,N)(NH3) (III), which was characterized by a combination of total correlation spectroscopy, double-quantum-filtered correlation spectroscopy, nuclear Overhauser effect spectrometry, and rotating-frame Overhauser enhancement spectroscopy experiments. Binding of the [Pt(PyAc-N,O)(NH3)]+ fragment to N7 of G(3) causes an increase of N-type character of the T(4) and G(3) deoxyribose residues relative to the unplatinated sequence, while those of T(1) and C(2) remain S-type. An internucleotide nuclear Overhauser effect between H6(4) and H2‘(3) indicates stacking between guanine and the 3‘-thymine base. The most striking feature proved to be the pronounced upfield shift and broadening of the 1H NMR signals assigned to the base protons H5 and H6 in III. Magnetization transfer between H5(2) and H3 of pyridine suggests that this effect is caused by base−base interactions involving the planar ligand on platinum, which must be situated on the 5‘ face of guanine. Possible implications for the DNA binding and cytotoxic effect of the compounds are discussed

Wired Multidecker Sandwich Assemblies. Stepwise Construction of a Hexanuclear Benzene-Centered Tris(alkynyl triple-decker) Complex¹

A complex containing three multidecker sandwich units anchored to a central benzene ring, 1,3,5-[Cp*Co(2,3-Et2C2B3H2-5-C⋮C)CoCp*]3C6H3 (8), has been synthesized via two different routes starting with the monomeric precursors closo-Cp*Co(Et2C2B4H3-5-I) or nido-Cp*Co(Et2C2B3H4-5-I), requiring four steps in each case. In both methods, the ethynyl-substituted species nido-Cp*Co(Et2C2B3H4-5-C⋮CH) was generated and treated with 1,3,5-triiodobenzene to give [nido-Cp*Co(2,3-Et2C2B3H5-5-C⋮C)]3C6H3, which was bridge-deprotonated and reacted with (Cp*CoCl)2 in THF solution to afford the target compound 8, which was characterized from multinuclear NMR, IR, UV−visible, and mass spectra, electrochemical data, and an X-ray diffraction study

(1,3-Dimethyluracil-5-yl)mercury(II): Preparative, Structural, and NMR Spectroscopic Studies of an Analog of CH₃Hg^II

The solution behavior of (1,3-DimeU-C5)Hg(CH3COO) (1a) (1,3-DimeU = 1,3-dimethyluracil) with regard to acetate replacement by anions X (Cl-, Br-, I-, NO3-, SCN-, CN-) and by other model nucleobases (1-methylcytosine, 1-MeC, 1-methyluracil, 1-MeUH, 1-methylthymine, 1-MeTH, 9-ethylguanine, 9-EtGH, and 2-thiouracil, 2-ThioUH) has been studied, primarily by means of 1H and 199Hg NMR spectroscopy. Moreover, the bis(1,3-DimeU-C5) complex of Hg has been crystallized and studied by X-ray crystallography. 7a:  orthorhombic system, space group Fdd2, a = 14.185(4) Å, b = 25.275(7) Å, c = 7.924(2) Å, V = 2840(2) Å3, Z = 8. The acetato ligand of 1a is readily displaced by anions X, frequently followed by disproportionation reactions leading to HgX2 and 7a. The donor atom X trans to C(5) has an effect on 3J coupling between 199Hg and H(6) of the 1,3-DimeU ligand according to NO3- > OAc- > Cl- ∼ Br- > I- > SCN- > CN- > 1,3-DimeU-C5 with extremes being 222 (X = NO3-) and 107 Hz (7a). In the presence of excess metal ions (Ag+, Hg2+), 1a forms hetero- and homonuclear derivatives with the second metal ion probably sitting at O(4). The mixed nucleobase complexes have the second base bound to Hg via N(3) (1-MeU (2a), 1-MeT (3a)), N(4) (1-MeC- (4a), 1-MeC (4b)), N(1) (9-EtG (5a)), N(7) (9-EtGH (5b)), and N(1), N(7) (9-EtG (5c)), as well as S(2) (2-ThioU (6a)). With the exception of the 9-ethylguanine complexes 5b and 5c, all the other complexes are inert on the 1H time scale. In several cases, e.g. 2a, 3a, 4a, and 5a, formation of dinuclear Hg or heteronuclear Ag and Pt derivatives has been established by multinuclear NMR spectroscopy

Organotransition-Metal Metallacarboranes. 59. Synthesis and Linkage of Boron-Functionalized Ferracarborane Clusters

Negishi cross-coupling has been applied to B−I and B−Br bonds in small closo-ferracarboranes as a means of effecting controlled substitution at boron, with subsequent linkage to form polymetallacarborane systems. Reaction of (η6-C6H6)Fe(2,3-Et2C2B4H3-5-I) (2) with vinyl−, butyl−, (trimethylsilyl)ethynyl−, and phenyl−organozinc reagents (RZnCl) in the presence of catalytic amounts of palladium(0) catalyst produced the corresponding B-functionalized derivatives (3−5 and 8, respectively) in moderate to good yields. Similarly, (η6-C6H6)Fe(Et2C2B4H3-7-C⋮CSiMe3) (12) was prepared from the B(7)−Br (11a) or B(7)−I derivative (11b). A second alkynyl fragment was introduced at B(5) on 12 to yield the B(5,7)-diethynyl-substituted compound 16. Treatment of (η6-C6H6)Fe(2,3-Et2C2B4H3-5-Ph) (8) with Cr(CO)6 in refluxing n-butyl ether gave the heterodimetallic complex (η6-C6H6)Fe[Et2C2B4H3-5-{(η6-C6H5)Cr(CO)3}] (9). A series of diferracarboranes bridged by thiophene (18), dihydrophenanthrene (19), or mono-, di-, or triphenylene (22−24) linking groups was generated via reaction of 2 with bis(chlorozinc) reagents and palladium(0) catalyst, as were B(5)−ferrocenyl derivatives (20, 21). Reaction of the known complex (η6-C8H10)Fe(Et2C2B4H4) with 8 at 180 °C formed (η6-C6H6)Fe(Et2C2B4H3-5-Ph)Fe(Et2C2B4H4) (25) via displacement of cyclooctatriene. Electrophilic B-iodination on the unsubstituted C2B4 cage of 25 afforded a dark red air-stable crystalline B(5)−iodo complex (26). Pd-catalyzed cross-coupling of 26 with PhZnCl, followed by cyclooctatriene displacement from (η6-C8H10)Fe(Et2C2B4H4), produced the triferracarborane-linked oligomer (η6-C6H6)Fe(Et2C2B4H3-5-Ph)Fe(Et2C2B4H3-5‘-Ph)Fe(Et2C2B4H4) (28) in an overall yield from 8 of 40% in this four-step sequence. Deprotection of 5 and 12 with fluoride gave the B(5)− and B(7)−C⋮CH derivatives 6 and 13, respectively. Homocoupling of these terminal alkynes with Pd/Cu catalyst afforded the linked isomers [(η6-C6H6)Fe(Et2C2B4H3-n-C⋮C)]2 (29, n = 5; 31, n = 7). Alternatively, 6 and 13 were treated with 1,3,5-C6H3I3 under similar conditions to form the benzene-centered triferracarborane complexes [(η6-C6H6)Fe(Et2C2B4H3-n-C⋮C)]3C6H3 (30, n = 5; 32, n = 7). X-ray diffraction analyses confirmed the structures of 9, 18, 24, and 26

Metal Complexes with Cis α Topology from Stereoselective Quadridentate Ligands with Amine, Pyridine, and Quinoline Donor Groups

Though the principles governing quadridentate topology and metal stereochemistry have been known for some time, the cis α topology has been little exploited in designing catalysts for asymmetric reactions. Investigation of the inorganic chemistry of labile metal cis α complexes was undertaken as a prelude to exploring their potential to serve as catalysts for a variety of different reactions. The synthesis of a series of first row transition metal complexes of quadridentate ligands with ethylenediamine (en) and S-propylenediamine (S-pn) backbones that have been alkylated at nitrogen with either pyridine (py) or quinoline (qn) donor groups as well as with noncoordinating benzyl (Bn) or pentafluorobenzyl (F5Bn) groups was undertaken. The steric and electronic properties vary throughout the ligand series, en(Bn)py, 1, en(F5Bn)py, 2, S-pn(F5Bn)py, 3, and S-pn(F5Bn)qn, 4. These ligands were reacted with MCln salts (n = 2, M = Mn, Fe, Co, Ni, Cu, Zn; n = 3, M = Fe) to generate, in most cases, octahedral complexes with the targeted cis α topology. UV/vis, NMR, IR, cyclic voltammetry (CV), and conductivity analysis are described for the metal compounds. X-ray structural analysis of [Cu{en(F5Bn)py}Cl]Cl reveals a five coordinate square pyramidal geometry. Single or major diastereomers were obtained for all diamagnetic Zn(II) complexes as well as for Co(III) analogues that were prepared by oxidation of Co(II) species using Br2 as the oxidant. Electronic differences among ligands are reflected in the oxidation potentials of the respective metal complexes as determined by CV, with fluorinated systems showing greater resistance to oxidation, as expected

Metal Complexes with Cis α Topology from Stereoselective Quadridentate Ligands with Amine, Pyridine, and Quinoline Donor Groups

Though the principles governing quadridentate topology and metal stereochemistry have been known for some time, the cis α topology has been little exploited in designing catalysts for asymmetric reactions. Investigation of the inorganic chemistry of labile metal cis α complexes was undertaken as a prelude to exploring their potential to serve as catalysts for a variety of different reactions. The synthesis of a series of first row transition metal complexes of quadridentate ligands with ethylenediamine (en) and S-propylenediamine (S-pn) backbones that have been alkylated at nitrogen with either pyridine (py) or quinoline (qn) donor groups as well as with noncoordinating benzyl (Bn) or pentafluorobenzyl (F5Bn) groups was undertaken. The steric and electronic properties vary throughout the ligand series, en(Bn)py, 1, en(F5Bn)py, 2, S-pn(F5Bn)py, 3, and S-pn(F5Bn)qn, 4. These ligands were reacted with MCln salts (n = 2, M = Mn, Fe, Co, Ni, Cu, Zn; n = 3, M = Fe) to generate, in most cases, octahedral complexes with the targeted cis α topology. UV/vis, NMR, IR, cyclic voltammetry (CV), and conductivity analysis are described for the metal compounds. X-ray structural analysis of [Cu{en(F5Bn)py}Cl]Cl reveals a five coordinate square pyramidal geometry. Single or major diastereomers were obtained for all diamagnetic Zn(II) complexes as well as for Co(III) analogues that were prepared by oxidation of Co(II) species using Br2 as the oxidant. Electronic differences among ligands are reflected in the oxidation potentials of the respective metal complexes as determined by CV, with fluorinated systems showing greater resistance to oxidation, as expected

Covalent and Noncovalent Interactions for [Metal(dien)nucleobase]²⁺ Complexes with l-Tryptophan Derivatives: Formation of Palladium−Tryptophan Species by Nucleobase Substitution under Biologically Relevant Conditions

The interaction of the complexes [Pd(dien)(1-MeCyt)]2+ (2) and [Pd(dien)(9-EtGH)]2+ (3) with the amino acids l-tryptophan (Trp) and N-acetyltryptophan (N-AcTrp) was studied and compared with the previously studied platinum analogues [Pt(dien)(1-MeCyt)]2+ (4) and [Pt(dien)(9-EtGH)]2+ (5). Solid-state structures for 2 and 4 are reported. For the palladium complexes, the interaction is pH sensitive. Below pH 5, the noncovalent interaction with stacking between the aromatic amino acid residue and the metalated nucleobase was observed. Fluorescence quenching experiments indicated similar association constants for platinum and palladium derivatives 2−5. Unusual substitution of the model nucleobases 1-methylcytosine (1-MeCyt) and 9-ethylguanine (9-EtGH) by tryptophan was observed in the range of pH 5−11. The resulting species [Pd(dien)(Trp)]+ (6) and [Pd(dien)(N-AcTrp)]+ (7) were characterized using 1H NMR, 13C NMR, and ESI-MS spectroscopy with coordination indicated through the amino and deprotonated amido nitrogens, respectively. Complexes 6 and 7 were also obtained from a solution of [Pd(dien)Cl]+ (1) incubated with either Trp or N-AcTrp, respectively

“Recapitation” of <i>nido</i>-Metallacarboranes as a Synthetic Tool: Preparation of Apically Substituted CoC₂B₄ Clusters via Boron Insertion¹

Derivatives of Cp*Co(2,3-Et2C2B4H4) containing substituents at the apex boron atom [B(7)], the first examples of apically functionalized small metallacarborane clusters, have been prepared in good yield via boron insertion into the nido-Cp*Co(2,3-Et2C2B3H3)2- dianion. Reaction of this substrate with BX3 (X = Cl, Br, I) or PhBCl2 in toluene at room temperature gave the corresponding Cp*Co(2,3-Et2C2B4H3-7-X) derivatives (2a−c and 3 in which X = Cl, Br, I, and Ph, respectively), all of which were isolated via column chromatography as air-stable yellow solids and characterized via 1H, 11B, and 13C NMR, infrared, UV−visible, and mass spectra. Treatment of the same dianion with 1,4-(Br2B)2C6H4 afforded air-stable orange crystalline [Cp*Co(2,3-Et2C2B4H3-7)]2C6H4 (4). The structure of this compound was defined via spectroscopy and X-ray crystallography as a bis(cobaltacarborane) complex linked at the apex borons via a 1,4-phenylene bridge. Crystal data for 4:  space group Pbca; a = 15.056(7) Å, b = 21.612 (8) Å, c = 11.641 (3) Å; Z = 4; R = 0.045 for 1582 independent reflections having I > 3σ(I)

Stereoselective Dihapto-Binding of Prochiral Aromatic Compounds by {TpRe(CO)(PMe₃)}: Synthesis, Characterization, Stability, and Enantiofacial Discrimination (Tp = Hydrido(tris)pyrazolylborate)

Synthetic access to {TpRe(CO)(PMe3)} and the ability of this fragment to bind unsaturated compounds are reported. A variety of complexes of the type TpRe(CO)(PMe3)(η2-L) (L = cyclohexene, cyclopentene, naphthalene, phenanthrene, thiophene, 2-methylthiophene, furan, or acetone) have been isolated and characterized, and stereochemical and stability issues of aromatic molecules bound to {TpRe(CO)(PMe3)} are discussed in detail. In particular, a solid-state structural study of TpRe(CO)(PMe3)(η2-cyclohexene) has provided a foundation for a discussion of the stereoelectronic features of the Re(I) fragment, and substitution reactions of an aromatic ligand by acetone provide insight into the stability of these aromatic complexes. In addition, a solid-state X-ray diffraction study of the Re(II) complex TpRe(CO)(PMe3)(OTf) (OTf = trifluoromethanesulfonate) is presented