Thomas W Stringfield

Preferred exocyclic-amino coordination of W(CO)5 on 2-aminopyrimidine and 4-aminopyrimidine vs. heterocyclic N-1 coordination for 2-aminopyridine

Abstract 2-Aminopyrimidine (2-ampym) and 4-aminopyrimidine (4-ampym) coordinate to W(CO) 5 predominantly via the exocyclic amino group (>91% in 10 min photolysis) rather than to the endocyclic N-1 position as found for 2-aminopyridine (2-ampy). Photolysis of W(CO) 6 in acetone in the presence of these ligands forms amino-bound [W(CO) 5 (2-ampym)] and [W(CO) 5 (4-ampym)] complexes. Secondary photolysis generates 18% (1.0 h photolysis) [W(CO) 4 (2-ampym)] or [W(CO) 4 (4-ampym)], chelated via the exocyclic amine and the adjacent endocyclic position (N-1 and N-3, respectively). Only ca. 10% of the more unhindered N-1-bound W(CO) 5 (4-ampym) was detected compared to virtually complete coordination via the exocyclic amino group for [W(CO) 5 (2-ampym)]. M mff 94 calculations show that the W(CO) 5 coordination to the exocyclic donor is favored by 98.8 and 95.6 kcal/mol over the adjacent endocyclic position in the 2-ampym and 4-ampym complexes, respectively. Calculated W–N bond lengths by the M mff 94 methods gave exo-amine W–N bond distances of 2.24 and 2.26 A and theoretical adjacent endocyclic W–N bond distances of 2.37 and 2.35 A ( isomers not observed from photolysis ) for the 2-ampym and 4-ampym complexes, respectively. A W–(N-1) bond of 2.28 A for this isomer of [W(CO) 5 (4-ampym)] was calculated. All W–N bonds are near the 2.18–2.33 A range (mean of 2.27±0.06) for [W(CO) 5 L] (L=pyridine, piperidine, glycine, 1-(2-py)-1,2,4-triazole, [W(CO) 5 CN] − , 5-MeU − ).

1H NMR and electrospray mass spectrometry of the mono-ionized bis(2,2'-bis(4,5-dimethylimidazole)chloronitrosylruthenium(II) complex ([Ru(NO)Cl(LH2)2]+, LH2 = 2,2'-bis(4,5-dimethylimidazole)

The reaction of RuCl3(NO)(H2O)2 with 2 equiv. of LH2=2,2′-bis(4,5-dimethylimidazole) in refluxing ethanol generates cis-[Ru(NO)Cl(LH2)2]2+ (1), analogous in structure to cis-[Ru(NO)Cl(bpy)2]2+, as the chloride salt. In 1, the methyl groups are differentiated into eight different 1H NMR magnetic environments. Substitution of 4,5-dimethyl-2,2′-biimidazole (L′H2), an 11.1% impurity in commercial LH2, occurred randomly with the undecorated ring diminishing the intensity of all eight resonances equally. The methyl group of the “out-of-plane” ring that hangs over the π orbitals of the NO+ ligand (CH3(6)) is shifted most upfield from 2.19 ppm of free LH2 and is assigned to the 1.23 ppm resonance. With the aid of 2-D NMR methods, we assign the following shifts. The ring donor opposite the {Ru(NO)}3+, CH3(7), should experience the greatest withdrawing influence, and is assigned as the origin of the 2.50 ppm resonance. Its ring partner, CH3(5), placed below another ring current, is assigned to the resonance at 2.13 ppm. 2-D NMR methods support the assignments of 1.39 ppm to CH3(1) and 2.09 ppm to CH3(2), the “in-plane-near” CH3 groups; 2.36 and 2.34 ppm to “in-plane-remote” CH3(3) and CH3(4); a 2.47 ppm shift is assigned to the remaining CH3(8). Because of the presence of the impurity L′H2 which has a substitution rate advantage (ca. 2.14-fold) due to a lower steric barrier for the unmethylated ring, the isolated product contained 62.4% (1a) [Ru(NO)Cl(LH2)2]Cl2, 31.9% (1b) [Ru(NO)Cl(LH2)(L′H2)]Cl2, and 5.7% (1c) [Ru(NO)Cl(L′H2)2]Cl2. The ESI MS spectrum exhibits parent 1+ ions (2a–c) in which one of the imidazole rings has been deprotonated. Thus, eight-line patterns for RuCl-containing fragments appear for m/z with z=1+ centered about 546 (2a), 518 (2b) and 490 (2c) in the intensity ratios of 1.000:0.511:0.091, respectively. The atomic composition for 2a was shown to be RuC20H27N9OCl (m/z=540.109049) by checking the “540” line of the isotopic bundle around m/z=546. The atomic composition of 2b was established from the “512” mass as RuC18H23N9OCl (m/z=512.077748) from the isotopic bundle around m/z=518. 2a–c undergo the loss of LH2 or L′H2 with low efficiency, but few other fragmentations were observed. Notably, the loss of NO or HCl are absent. 2a–c have good π-donating imidazole and imidazolato functionalities which suppress NO loss. IR laser loss experiments on 2a in the mass spectral cavity were unable to identify a frequency value that selectively dissociates NO. Rather, complete fragmentation of the complexes 2a–c occurred at energies sufficient to induce any ligand dissociation; the parent ions being very robust. The 1H NMR data are supported by an MMFF94 energy-minimized structure for 1 and its theoretical trans isomer.

Absence of 1,3-metallotropic shifts in M(CO)5 complexes of pyrimidine and 1,3,5-triazine (M=W, Mo, Cr)

Abstract M(CO) 5 L complexes with M=W 0 , Mo 0 and Cr 0 and L=pyrimidine and 1,3,5-triazine were prepared by photochemical generation from the parent M(CO) 6 complexes in acetone. All six complexes are not fluxional among available N-donor sites from room temperature up to ca. 60°C in CDCl 3 , and do not undergo rapid exchange with external excess free ligand. Thus, as in the case of the W(CO) 5 L complexes, a one-bond migration between N sites in a diazine occurs readily for pyridazine (e.g. a 1,2-metallotropic shift has been reported), but two-bond migrations for a 1,3-metallotropic shift is not seen with pyrimidine or triazine, just as the three-bond migration for a 1,4-metallotropic shift was not observed previously for the pyrazine complexes. The decomposition processes of the M(CO) 5 L complexes in CDCl 3 with pyrazines is known to follow the order Cr (minutes lifetime)⪢Mo (several hours)>W (days to weeks duration), but for the pyrimidine and 1,3,5-triazine complexes Cr and W are of comparable stability (stable for 1–2 weeks), and more so than the Mo analogue (stable for about 7–8 h). 1 H NMR data on all six complexes show that protons α to the site of metallation are shifted downfield by 0.27–0.36 ppm compared to the free ligand. The magnitude of Δ δ for the effect of metals on the chemical shift follow the order W>Mo>Cr. The more remote H4 protons of pyrimidine or triazine exhibit the smallest downfield shift upon metallation by the M(CO) 5 moiety. For the Cr(CO) 5 derivative the H4 proton of pyrimidine and H5 of triazine are shifted upfield. The upfield shift effect for the H5, near absence of a net effect for H4 of pyrimidine, and the upfield shift observed for H4 of the triazine complex of the Cr series are attributed mainly to a strong resonance component with dπ back-donation for the Cr derivative, as well as a possible TIP influence on the chemical shift parameter, contributions that are attenuated for the Mo and W complexes with higher energy excited states. No evidence for η 2 -type coordination for these d 6 complexes was obtained in contrast to Ru(II) d 6 chemical relatives which adopt η 2 coordination to pyrimidines.

Coordination of W(CO)5 to DNA and RNA nucleobases: development of a possible heavy-metal labeling complex

Photolysis of W(CO)6 in acetone solvent in the presence of DNA/RNA nucleobases attached to their ribose sugars has revealed attachment of the W(CO)5 moiety at N-7, N-1 and N-3 for both guanosine (G) and adenosine (A). Cytidine (C) coordinates only at N-3. Thymidine (T) and uridine (U) do not coordinate via a pyrimidine site, but engage in attack at the C3′ ribose position to form a carbene. The isomer distribution of W(CO)5 to G and A follows a pattern recently discovered for RuII of [Ru(hedta)]− in that the softer metal centers (compared to PtII agents) favor binding at N-3 over N-7 in a ratio close to 70:30 for RuII on G, matched by a 72:28 ratio for W(CO)5 with G and 78:22 with A where the ratio represents N-3 plus N-1 coordination : N-7 coordination for the W(CO)5 series. The results indicate the possibility of developing a water-soluble L′W(CO)4 heavy atom attachment for X-ray structural uses or as a metallo-drug wherein L′ serves as a solubilizing, trans directing agent in the photolysis of W(CO)5L′.

Tipping the energy balance toward exocyclic-amino coordination of W(CO)5 by methylation of the amino group of 2- and 4-aminopyridines, but not with adenosine

Abstract 2-Aminopyridine (2-ampy) substitutes on [W(CO) 5 (acetone)] or [W(CO) 5 (thf)] to produce 100% endocyclic N-1 coordinated [W(CO) 5 (2-ampy)]. Both N-1 coordinated and exocyclic-amine-bound isomers of [W(CO) 5 (4-ampy)] are formed by the substitution of 4-aminopyridine (4-ampy) on [W(CO) 5 (acetone)] in the ratio of 58% exo-amine coordination: 42% endocyclic amine under kinetic control. The distribution adjusts by linkage isomerism over 15 days to >86% exo-amine bound for the thermodynamic distribution. Within limit of 1 H NMR detection >95% exo-amine coordination occurs for 4-(dimethylamino)pyridine (4-Me 2 ampy), in spite of increased steric hindrance. Coordination of 2-(dimethylamino)pyridine to W(CO) 5 occurs only as the exo-amine donor, reversing the observations of the 2-ampy case. Coordination of W(CO) 5 with adenosine takes place with purine ring N donors (45% N-1, 33% N-3, and 22% N-7). The monomethylated N 6 -methyladenosine produced only N-1 coordination in low yield. Apparently steric blocking by the N 6 -methyl group retards coordination at N-7, and hydrogen bonding of the 5′- alcohol to N-3 of the purine ring in response to enhanced basicity of the N-3 site upon methylation of the exo-amine retards addition at N-3 for [W(CO) 5 ( N 6 -methyladenosine)]. Surprisingly in relation to the effects of amino methylation for the simple aminopyrimidines where W(CO) 5 adopts >91% of 2-ampym and 100% of 4-ampym coordination via the exo-amine, N-1 is the preferred site of coordination for adenosines over the exo-amine position. The known releasing effect of the five-member portion of the adenine ring, enhancing σ basicity at N-1 is not overcome by N 6 -methylation which directs much of its enhancement of ring basicity to N-3. N 6 , N 6 -Dimethyladenosine produced no coordination with W(CO) 5 under equivalent photosynthetic conditions; the second methyl group only provides additional steric hindrance to coordination at N-1, showing the powerful influence of conjugation of the amino lone pair with the purine ring in preventing a sufficiently basic exo-amine that can coordinate W(CO) 5 in contrast to the outcome with the analogous pyridine (2-Me 2 ampy). Acetylation of 4-ampy (4-acetamidopyridine=4-Acampy) should favor the pyridyl coordination; however, coordination to the carbonyl group is observed for [W(CO) 5 (4-Acampy)].

Formation of a W(CO)5–furanosylidene complex from ribose without the use of protective groups

Abstract [W(CO)5(acetone)], formed by photolysis of W(CO)6, undergoes a spontaneous reaction at the C-1 position of d -ribose in d6-acetone in 24 h in quantitative yield to form water and the W(CO)5–furanosylidene complex, exhibiting a characteristic carbene 13C resonance at 427 ppm. The reaction proceeds without protection of any of the ribose hydroxyl groups, and occurs only at the C-1 position. The same reaction does not occur for fructose, d (+)-ribonic γ-lactone, or 2-deoxy- d -ribose. No reaction occurred with the pyranose sugars, d -glucose or d -galactose. A pathway via oxidative addition to CH of the open chain aldehyde form of ribose is proposed. Insertion of W(CO)5 into the CH bond, followed by rearrangement of the W(II)(CO)5–acyl hydride to a hydroxy carbene that recyclizes to the coordinated furanosylidene accounts for the reactivity of d -ribose and the absence of reactivity for the other sugars. Molecular mechanics calculations were carried out using spartan and mmff 94 programs for the free sugars d -ribose and d -glucose and their C-1-coordinated carbenes of W(CO)5. The carbene complexes are energetically uphill of the free sugars by 54.8 and 63.3 kcal mol−1 for ribose and glucose, respectively. Therefore, elimination of water is a key factor in the net driving force to form the coordinated carbene of d -ribose. The structures reveal a useful planarity at C-1 which places the filled p-orbital on the O atom alpha to the carbene in the proper perpendicular arrangement to maximize resonance with the carbene carbon. The theoretical structure for the d -glucose analogue adopts sufficient puckering of the chair arrangement of the glucose to cause a misalignment of the alpha O p-orbital, which would decrease the inherent stablity, consistent with the absence of forming such a species.