Titanium(II) Porphyrin Complexes: Versatile One- and Two-Electron Reducing Agents. Reduction of Organic Chlorides, Epoxides, and Sulfoxides

Treatment of the well-defined complexes (TTP)Ti(η2-EtC⋮CEt) or trans-(TTP)Ti(THF)2 with vicinal dichloroalkanes or dichloroalkenes results in the production of alkenes or alkynes and 2 equiv of (TTP)TiCl. This net two-electron redox reaction arises from two formal one-electron reduction processes mediated by chlorine atom transfer. Oxygen atom transfer occurs when the Ti(II) porphyrins are treated with several different sulfoxides or epoxides, resulting in two-electron redox products, (TTP)TiO, the sulfide or alkene, and EtC⋮CEt or THF. The electronic properties of the substituents on the sulfoxides or epoxides correlate with the yield and rate of the deoxygenation reactions

Decamethylnickelocenium hydrogen-7,7,8,8-tetracyanoperfluoro-p-quinodimethandiide: isolation of the protonated weak base [HTCNQF4]-

Journal ArticleUnprecedently stable hydrogen-7,7,8,8- tetracyanoperfluoro-p-quinodimethandiide, [HTCNQF4]-, is isolated and crystallographically characterized

Facile Syntheses of Titanium(II), Tin(II), and Vanadium(II) Porphyrin Complexes through Homogeneous Reduction. Reactivity of trans-(TTP)TiL2 (L = THF, t-BuNC)

Facile syntheses of the meso-tetra-p-tolylporphyrin (TTP) complexes trans-(TTP)Ti(THF)2(1), (TTP)Sn (2), and trans-(TTP)V(THF)2 (3) are achieved through homogeneous reduction of high-valent precursors using NaBEt3H. The composition of the new compound trans-(TTP)Ti(THF)2 was determined by spectroscopic and chemical characterization. Ligand displacement reactions of trans-(TTP)Ti(THF)2 with t-BuNC produced a new Ti(II) complex,trans-(TTP)Ti(t-BuNC)2. The ligand-binding preference of (TTP)TiIILn (n = 1, 2) is picoline ∼pyridine \u3e t-BuNC \u3e PhC⋮CPh \u3e EtC⋮CEt \u3e THF

DeepCBS: shedding light on the impact of mutations occurring at CTCF binding sites

CTCF-mediated chromatin loops create insulated neighborhoods that constrain promoter-enhancer interactions, serving as a unit of gene regulation. Disruption of the CTCF binding sites (CBS) will lead to the destruction of insulated neighborhoods, which in turn can cause dysregulation of the contained genes. In a recent study, it is found that CTCF/cohesin binding sites are a major mutational hotspot in the cancer genome. Mutations can affect CTCF binding, causing the disruption of insulated neighborhoods. And our analysis reveals a significant enrichment of well-known proto-oncogenes in insulated neighborhoods with mutations specifically occurring in anchor regions. It can be assumed that some mutations disrupt CTCF binding, leading to the disruption of insulated neighborhoods and subsequent activation of proto-oncogenes within these insulated neighborhoods. To explore the consequences of such mutations, we develop DeepCBS, a computational tool capable of analyzing mutations at CTCF binding sites, predicting their influence on insulated neighborhoods, and investigating the potential activation of proto-oncogenes. Futhermore, DeepCBS is applied to somatic mutation data of liver cancer. As a result, 87 mutations that disrupt CTCF binding sites are identified, which leads to the identification of 237 disrupted insulated neighborhoods containing a total of 135 genes. Integrative analysis of gene expression differences in liver cancer further highlights three genes: ARHGEF39, UBE2C and DQX1. Among them, ARHGEF39 and UBE2C have been reported in the literature as potential oncogenes involved in the development of liver cancer. The results indicate that DQX1 may be a potential oncogene in liver cancer and may contribute to tumor immune escape. In conclusion, DeepCBS is a promising method to analyze impacts of mutations occurring at CTCF binding sites on the insulator function of CTCF, with potential extensions to shed light on the effects of mutations on other functions of CTCF

Titanium(II) Porphyrin Complexes: Versatile One- and Two-Electron Reducing Agents. Reduction of Organic Chlorides, Epoxides, and Sulfoxides

Treatment of the well-defined complexes (TTP)Ti(η2-EtC⋮CEt) or trans-(TTP)Ti(THF)2 with vicinal dichloroalkanes or dichloroalkenes results in the production of alkenes or alkynes and 2 equiv of (TTP)TiCl. This net two-electron redox reaction arises from two formal one-electron reduction processes mediated by chlorine atom transfer. Oxygen atom transfer occurs when the Ti(II) porphyrins are treated with several different sulfoxides or epoxides, resulting in two-electron redox products, (TTP)TiO, the sulfide or alkene, and EtC⋮CEt or THF. The electronic properties of the substituents on the sulfoxides or epoxides correlate with the yield and rate of the deoxygenation reactions.Reprinted (adapted) with permission from Journal of Organic Chemistry 63 (1998): 356, doi:10.1021/jo971893p. Copyright 1998 American Chemical Society.</p

Does the Ruthenium Nitrato Catalyst Work Differently in <i>Z</i>‑Selective Olefin Metathesis? A DFT Study

In the new class of N-heterocyclic carbene (NHC) chelated ruthenium catalysts for <i>Z</i>-selective olefin metathesis, the nitrato-supported complex <b>3cat</b> appears distinct from all the other carboxylato-supported analogues. We have performed DFT calculations (B3LYP and M06) to elucidate the mechanism of <b>3cat</b>-catalyzed metathesis homodimerization of 3-phenyl-1-propene. The six-coordinate <b>3cat</b> transforms via initial dissociation and isomerization into a trigonal-bipyramidal intermediate (<b>5</b>), from which two consecutive metathesis reactions via the side-bound mechanism lead to (<i>Z</i>)-PhCH₂CHCHCH₂Ph (major) and (<i>E</i>)-PhCH₂CHCHCH₂Ph (minor). In the overall mechanism, <b>3cat</b> functions similarly to the pivalate-supported analogue <b>1cat</b>. The substitution of a smaller nitrato group does not change the side-bound olefin attack mechanism for either the initiation or homocoupling metathesis. The chelation of the NHC ligand causes this class of Ru catalysts to favor the side-bound over the bottom-bound mechanism. The calculated energetics corroborate the experimental observation that <b>3cat</b> is somewhat more active than <b>1cat</b> in catalyzing the homodimerization of 3-phenyl-1-propene

Facile Syntheses of Titanium(II), Tin(II), and Vanadium(II) Porphyrin Complexes through Homogeneous Reduction. Reactivity of trans-(TTP)TiL2 (L = THF, t-BuNC)

Facile syntheses of the meso-tetra-p-tolylporphyrin (TTP) complexes trans-(TTP)Ti(THF)2(1), (TTP)Sn (2), and trans-(TTP)V(THF)2 (3) are achieved through homogeneous reduction of high-valent precursors using NaBEt3H. The composition of the new compound trans-(TTP)Ti(THF)2 was determined by spectroscopic and chemical characterization. Ligand displacement reactions of trans-(TTP)Ti(THF)2 with t-BuNC produced a new Ti(II) complex,trans-(TTP)Ti(t-BuNC)2. The ligand-binding preference of (TTP)TiIILn (n = 1, 2) is picoline ∼pyridine > t-BuNC > PhC⋮CPh > EtC⋮CEt > THF.Reprinted (adapted) with permission from Inorganic Chemistry 37 (1998): 5, doi:10.1021/ic970961n. Copyright 1998 American Chemical Society.</p

A Thorough DFT Study of the Mechanism of Homodimerization of Terminal Olefins through Metathesis with a Chelated Ruthenium Catalyst: From Initiation to <i>Z</i> Selectivity to Regeneration

Density functional theory (DFT) calculations (B3LYP, M06, and M06-L) have been performed to investigate the mechanism and origins of <i>Z</i> selectivity of the metathesis homodimerization of terminal olefins catalyzed by chelated ruthenium complexes. The chosen system is, without any simplification, the experimentally performed homocoupling reaction of 3-phenyl-1-propene with <b>1cat</b>, a pivalate and N-heterocyclic carbene (NHC) chelated Ru precatalyst. The six-coordinate <b>1cat</b> converts to a trigonal-bipyramidal intermediate (<b>3</b>) through initial dissociation and isomerization. The metathesis reaction of complex <b>3</b> with 3-phenyl-1-propene occurs in a side-bound mechanism and generates the trigonal-bipyramidal Ru–benzylidene complex <b>6</b>. Complex <b>6</b> is the active catalyst for the subsequent side-bound metathesis with 3-phenyl-1-propene, which forms metallacyclobutanes that lead to the (<i>Z</i>)- and (<i>E</i>)-olefin homodimers. The transition states of cycloreversion leading to the (<i>Z</i>)- and (<i>E</i>)-olefins differ in energy by 2.2 kcal/mol, which gives rise to a calculated <i>Z</i> selectivity that agrees with experimental results. The <i>Z</i> selectivity stems from reduced steric repulsion in the transition state. The regeneration of complex <b>6</b> occurs along with the formation of the gaseous byproduct ethylene, whose evolution drives the overall reaction. As our results indicate, the chelating ligands are crucial for this new class of Ru catalysts to achieve <i>Z</i>-selective olefin metathesis, because they direct olefin attack, differentiate energies of the transition states and intermediates, and support the complexes in certain coordination geometries

Mechanism and Origins of <i>Z</i> Selectivity of the Catalytic Hydroalkoxylation of Alkynes via Rhodium Vinylidene Complexes To Produce Enol Ethers

We report the first theoretical study of transition-metal-catalyzed hydroalkoxylation of alkynes to produce enol ethers. The study utilizes density functional theory calculations (M06) to elucidate the mechanism and origins of <i>Z</i> selectivity of the anti-Markovnikov hydroalkoxylation of terminal alkynes with a Rh­(I) 8-quinolinolato carbonyl chelate (<b>1cat</b>). The chosen system is, without any truncation, the realistic reaction of phenylacetylene and methanol with <b>1cat</b>. Initiation of <b>1cat</b> through phenylacetylene substitution for carbonyl generates the active catalyst, a Rh­(I) η²-alkyne complex (<b>3</b>), which tautomerizes via an indirect 1,2-hydrogen shift to the Rh­(I) vinylidene complex <b>4</b>. The oxygen nucleophile methanol attacks the electrophilic vinylidene C_α, forming two stereoisomeric Rh­(I) vinyl complexes (<b>15</b> and <b>16</b>), which ultimately lead to the (<i>Z</i>)- and (<i>E</i>)-enol ether products. These complexes undergo two ligand-mediated proton transfers to yield Rh­(I) Fischer carbenes, which rearrange through a 1,2-β-hydrogen shift to afford complexes with π-bound product enol ethers. Final substitution of phenylacetylene gives (<i>Z</i>)- and (<i>E</i>)-PhCHCHOMe and regenerates <b>3</b>. The anti-Markovnikov regioselectivity stems from the Rh­(I) vinylidene complex <b>4</b> with reversed C_α and C_β polarity. The stereoselectivity arises from the turnover-limiting transition states (TSs) for the Rh­(I) carbene rearrangement: the <i>Z</i>-product-forming <b>TS24</b> is sterically less congested and hence more stable than the <i>E</i>-product-forming <b>TS25</b>. The difference in energy (1.2 kcal/mol) between <b>TS24</b> and <b>TS25</b> gives a theoretical <i>Z</i> selectivity that agrees well with the experimental value. Calculations were also performed on the key TSs of reactions involving two other alkyne substrates, and the results corroborate the proposed mechanism. The findings taken together give an insight into the roles of the rhodium–quinolinolato chelate framework in directing phenylacetylene attack by trans effect, mediating hydrogen transfers through hydrogen bonding, and differentiating the energies of key TSs by steric repulsion