Peter P.-Y. Chen

Metal-free arylation of benzene and pyridine promoted by amino-linked nitrogen heterocyclic carbenes

An amino-linked nitrogen heterocyclic carbene (amino-NHC), 1-tBu, has been shown to mediate carbon-carbon coupling through the direct C-H functionalization of benzene and pyridine in the absence of a metal catalyst. Using EPR, the first spectroscopic evidence corroborating the single electron transfer mechanism for the metal-free carbon-carbon coupling manifold, as reported by others, is introduced.

Facile O-atom insertion into C C and C H bonds by a trinuclear copper complex designed to harness a singlet oxene

Two trinuclear copper [CuICuICuI(L)]1+ complexes have been prepared with the multidentate ligands (L) 3,3′-(1,4-diazepane-1,4-diyl)bis(1-((2-(dimethylamino)ethyl)(methyl)amino)propan-2-ol) (7-Me) and (3,3′-(1,4-diazepane-1,4-diyl)bis(1-((2-(diethylamino) ethyl)(ethyl) amino)propan-2-ol) (7-Et) as models for the active site of the particulate methane monooxygenase (pMMO). The ligands were designed to form the proper spatial and electronic geometry to harness a “singlet oxene,” according to the mechanism previously suggested by our laboratory. Consistent with the design strategy, both [CuICuICuI(L)]1+ reacted with dioxygen to form a putative bis(μ3-oxo)CuIICuIICuIII species, capable of facile O-atom insertion across the central CC bond of benzil and 2,3-butanedione at ambient temperature and pressure. These complexes also catalyze facile O-atom transfer to the CH bond of CH3CN to form glycolonitrile. These results, together with our recent biochemical studies on pMMO, provide support for our hypothesis that the hydroxylation site of pMMO contains a trinuclear copper cluster that mediates CH bond activation by a singlet oxene mechanism.

Alkane Oxidation: Methane Monooxygenases, Related Enzymes, and Their Biomimetics

Methane monooxygenases (MMOs) mediate the facile conversion of methane into methanol in methanotrophic bacteria with high efficiency under ambient conditions. Because the selective oxidation of methane is extremely challenging, there is considerable interest in understanding how these enzymes carry out this difficult chemistry. The impetus of these efforts is to learn from the microbes to develop a biomimetic catalyst to accomplish the same chemical transformation. Here, we review the progress made over the past two to three decades toward delineating the structures and functions of the catalytic sites in two MMOs: soluble methane monooxygenase (sMMO) and particulate methane monooxygenase (pMMO). sMMO is a water-soluble three-component protein complex consisting of a hydroxylase with a nonheme diiron catalytic site; pMMO is a membrane-bound metalloenzyme with a unique tricopper cluster as the site of hydroxylation. The metal cluster in each of these MMOs harnesses O2 to functionalize the C-H bond using different chemistry. We highlight some of the common basic principles that they share. Finally, the development of functional models of the catalytic sites of MMOs is described. These efforts have culminated in the first successful biomimetic catalyst capable of efficient methane oxidation without overoxidation at room temperature.

Development of the Tricopper Cluster as a Catalyst for the Efficient Conversion of Methane into MeOH

Following recent progress towards understanding the structure of the particulate methane monooxygenase in methanotrophic bacteria, it is now possible to attempt the development of laboratory catalysts for the conversion of methane into MeOH under ambient conditions. To this end, a class of tricopper complexes that are capable of efficiently oxidizing small hydrocarbon substrates at room temperature has recently been developed. In this Minireview, we describe the development of a tricopper cluster to accomplish the catalytic conversion of methane into MeOH, as well as a number of small n‐alkanes into their corresponding alcohols and ketones, with high efficiencies. The properties of this robust catalytic system are discussed.

Paramagnetic NMR Shifts for Saddle-Shaped Five-Coordinate Iron(III) Porphyrin Complexes with Intermediate-Spin Structure†

The five-coordinate saddle-shaped iron(III) porphyrin complex, Fe(OETPP)Cl, has been identified as an admixed (S = 3/ 2, 5/2) spin electronic structure which can be used as a model for cytochrome c’ (OETPP = dianion of 2,3,7,8,12,13,17,18octaethyl-5,10,15,20-tetraphenylporphyrin). It has also been conjectured that a saddle deformation of the macrocycle results in a symmetry reduction, that is, a C2v local symmetry, to raise the dx2 y2 orbital energy by spatial mixing of the dx2 y2 and dz2 orbitals as shown by early spin-restricted ZINDO calculations. Nevertheless, the definite composition, which is a mixture of the S = 3/2 and S = 5/2 spin states, still remains debatable. When the axial ligand is changed from the Cl ion to a weaker ligand ClO4 , Fe(OETPP)ClO4 recently has been characterized by a pure intermediate-spin state (S = 3/2) electronic structure. 6] Generally, the properties determined by Mçssbauer spectroscopy, EPR and magnetic susceptibility measurements in the series of Fe(OETPP)X (X = Cl, Br, I, ClO4) complexes are similar to planar five-coordinate iron(III) porphyrin complexes. However, with careful examination of their paramagnetic NMR shifts, they exhibit a distinct difference in the C NMR shifts at the meso-C position, which is important for analyzing the bonding interactions between a metal center and a porphyrin macrocycle. For planar porphyrin ligands, such as high-spin FeTPPCl (or FeOEPCl), the meso-C signal appears at a downfield position of 500 ppm (or 380 ppm), and 368 ppm (or 246 ppm) for the admixed (5/2, 3/2) FeTPPClO4 (or FeOEPClO4), respectively (see Table 1; TPP = dianion of 5,10,15,20-tetraphenylporphyrin and OEP = dianion of 2,3,7,8,12,13,17,18-octaethylporphyrin). 12] These downfield shifts at the meso-C atoms have been attributed by Cheng et al. to interactions between the iron(III) dz2 and the porphyrin a2u orbitals. [13] However, for saddled porphyrin ligands, considering the main skeleton of the macrocycle, the five-coordinate saddleshaped Fe(OETPP)Cl has a local C2v symmetry, which is lower than the C4v symmetry of five-coordinate planar iron(III) porphyrin complexes. Theoretically, Fe(OETPP)Cl shall have similar bonding interactions as found for a C4v symmetry. For example, the downfield shifts of 450 ppm for the meso-C atom, 525, 642 ppm for a-C atoms, and 973 ppm for b-C atoms of saddled Fe(OETPP)Cl are similar to those of planar five-coordinate iron(III) porphyrin complexes with admixed intermediate-spin states. The concept of dz2 –a2u interactions seems to apply to the case of Fe(OETPP)Cl for its downfield-shifted meso-C signal as well. Yet, in the case of Fe(OETPP)ClO4, the meso-C signal was found at an unusual upfield position at 47 ppm. 15] The C NMR signal for the meso-C atoms shifted upfield about 500 ppm as the axial ligand was changed from Cl to ClO4 . This shift is much larger than the average change of 132 ppm in planar fivecoordinate iron(III) porphyrin complexes bearing the same axial ligands (see Table 1). This characteristic for the saddled porphyrin ligand implies that the dz2 –a2u interaction vanishes or is greatly weakened when the spin state changes to a pure S = 3/2 state. Normally, the disappearance of bonding interactions was found when the coordination number was altered as, for example, from a fiveto a six-coordinate iron(III) porphyrin complex. However, although the crystal structure of Fe(OETPP)ClO4 still shows the five-coordinate saddled shape with a C2v local symmetry which resembles Fe(OETPP)Cl, obviously the dz2 –a2u interaction is not sufficient to simultaneously interpret both saddled complexes. This difference between Fe(OETPP)Cl and Fe(OETPP)ClO4 has not been observed for five-coordinate planar iron(III) Table 1: C NMR chemical shifts dobs and (isotropic shifts, diso) [a] of fivecoordinate complexes.

The MoMo Quintuple Bond as a Ligand to Stabilize Transition-Metal Complexes†

Herein, we report the employment of the Mo-Mo quintuple bonded amidinate complex to stabilize Group 10 metal fragments {(Et3P)2M} (M=Pd, Pt) and give rise to the isolation of the unprecedented δ complexes. X-ray analysis unambiguously revealed short contacts between Pd or Pt and two Mo atoms and a slight elongation of the Mo-Mo quintuple bond in these two compounds. Computational studies show donation of the Mo-Mo quintuple-bond δ electrons to an empty σ orbital on Pd or Pt, and back-donation from a filled Pd or Pt dπ orbital into the Mo-Mo δ* level (LUMO), consistent with the Dewar-Chatt-Duncanson model.

Copper–obatoclax derivative complexes mediate DNA cleavage and exhibit anti-cancer effects in hepatocellular carcinoma

Obatoclax is an indole-pyrrole compound that induces cancer cell apoptosis through targeting the anti-apoptotic Bcl-2 protein family. Previously, we developed a series of obatoclax derivatives and studied their STAT3 inhibition-dependent activity against cancer cell lines. The obatoclax analog, prodigiosin, has been reported to mediate DNA cleavage in cancer cells by coordinating with copper complexes. To gain an understanding of copper-obatoclax complex activity, we applied obatoclax derivatives to examine their copper-mediated nuclease activity as a means to establish a basis for structure activity relationship. Replacement of the indole ring of obatoclax with furanyl, thiophenyl or Boc-indolyl rings reduced the DNA cleavage ability. The same effect was achieved through the replacement of the obatoclax pyrrolyl ring with thiazolidinedione and thioacetal. Among the compounds tested, we demonstrated that the complex of obatoclax or compound 7 with copper exhibited potent DNA strand scission which correlated with HCC cell growth inhibition.