Pyr Complex Research Articles

The association of π–π stacking and hydrogen bonding interactions in substituted Rebek imide with 2,6-di(isobutyramido)pyridine rings: theoretical insight into X-Rebek imide||pyr complexes

A host–guest model designed between two hemispheres as Rebek imide receptor and different ligands via triple hydrogen bonding and π−π stacking interactions was surveyed to investigate the substituent effects. The association of Rebek imide with 2,6-di(isobutyramido)pyridine (X-Rebek imide||pyr) in the presence of electron donating/withdrawing substituents was studied (X = (NCH3)2, OCH3, CH3, OH, H, F, Cl, Br and CN, CF3 and NO2, where || and ∙∙∙ denote π–π stacking and hydrogen bonding). It was explained the variation in binding energies, energy decomposition, geometries, NMR properties, and electron density of mentioned complexes and effect of different types of the substituents in studied complexes was identified via computational chemistry at M05-2X/6-311++G** level of theory on π–π stacking and hydrogen bonding interactions.

Mutual cooperation of π-π stacking and pnicogen bond interactions of substituted monomeric Lawesson’s reagent and pyridine rings: Theoretical insight into Pyr||X-PhPS2⊥pyr complexes

The simultaneous cooperation of π-π stacking and pnicogen bonding the formation of Pyr||X-PhPS2⊥Pyr ternary complexes has been investigated via a computational chemistry at MP2/aug-cc-pVDZ level of theory. We proved by computational NMR data the effect of electron-withdrawing and donating substituents on 1pJ(N-P) across 15N⋯31P pnicogen bond. The interactionenergy contributions of Pyr||X-PhPS2 and X-PhPS2⊥Pyr dimers have been investigated by symmetry adapted perturbation theory (SAPT) energy decomposition method. In addition, atoms in molecules (AIM), natural bond orbital analysis (NBO) and molecular electrostatic potentials (MEP) have been performed to unveil the mechanism of these interactions in the title complexes.

Effect of Blocking PYR Complex Binding to DNA Site by Peptide Nucleic Acid on γ-Globin Gene Expression

To investigate the effect of blocking polypyrimidine complex binding to DNA site by using peptide nucleic acid (PNA) on γ-globin gene expression. PYR-PNA, β-PNA and RS-PNA (random sequence-PNA) were designed and synthesized, then were transfected into K562 cells with the cationic liposome lipofectamine 2000 used as vector. The expression of γ-globin gene at both the transcriptional and translational level was detected by RT-PCR and the Western blot respectively at 24 h, 48 h and 72 h after transfection with PNAs. Compared with RS-PNA and control groups, the expression of γ-globin gene at mRNA and protein levels in PYR-PNA group was significantly up-regulated(P<0.05), especially at 48 h after tranfection, the levels of mRNA and protein in PYR-PNA group were increased by 2.0 and 2.5 times than those in control group, respectively. PYR-PNA can significantly up-regulate the expression of γ-globin gene in K562 cells, this study may provide a new research idea for gene therapy of β-thalassemia.

Mutual interplay between pnicogen–π and tetrel bond in PF3⊥X–Pyr…SiH3CN complexes: NMR, SAPT, AIM, NBO, and MEP analysis

The mutual interplay between pnicogen–π and tetrel bond in the formation of PF3⊥X–Pyr…SiH3CN ternary complexes has been investigated via a computational chemistry at MP2/aug-cc-pVDZ level of theory. We proved by computational NMR data the effect of electron-withdrawing and electron-donating substituents on 1tJ(N-Si) across 15N...35Si tetrel bonds was investigated at M06-2X/aug-cc-pVDZ levels of theory in PF3⊥CN–Pyr…SiH3CN complex. The nature of the interactions has been studied by means of symmetry-adapted perturbation theory (SAPT) and molecular electrostatic potentials (MEP). The electrostatic interaction played a major role in the change of tetrel bond interaction strength in the X–Pyr…SiH3CN binary systems, whereas the change of pnicogen–π strength in the PF3⊥X–Pyr complexes was caused jointly by the dispersion interactions. Energy decomposition indicates that the percentage of the electrostatic term in the tetrel bond system constitutes in the total attractive binding energies, while the percentage of the dispersion term in the pnicogen bonding constitutes in the attractive binding energies. In addition, atoms in molecules (AIM) and natural bond orbital (NBO) analyses were also performed to unveil the mechanism of these interactions in the title complexes.

Cyclization of Synthetic seco‐Proansamitocins to Ansamitocin Macrolactams by Actinosynnema pretiosum as Biocatalyst

Cyclization of Synthetic <i>seco</i>‐Proansamitocins to Ansamitocin Macrolactams by <i>Actinosynnema pretiosum</i> as Biocatalyst

Degradation of atrazine photoinduced by Fe(III)–pyruvate complexes in the aqueous solution

The composition and photochemical properties of the Fe(III)–Pyr complexes in the aqueous solution was studied in this work. Fe(III) was complexed by Pyr in the ratio of 1:3. The photochemical processes occurred in the Fe(III)–Pyr system was studied in detail. Fe(II) was the main intermediate product. DMPO was used as scavenger to determine the active radicals, such as OH, CO 3 −, CO 2 −, H and RCO 2 by ESR. Photodegradation of atrazine induced by the photolysis of Fe(III)–Pyr was studied and the reaction kinetics fitted the first order reaction. Parameters such as pH, the initial concentrations of Fe(III), pyruvate (Pyr) and atrazine were all investigated. Photoproducts were detected by the LC–MS and the photodegradation scheme was proposed. OH radical was the main pathway of atrazine degradation.

Cooperativity of π-stacking and hydrogen bonding interactions and substituent effects on X-ben‖pyr⋯H–F complexes

Quantum chemical calculations have been performed to gauge the effect of pi-stacking and hydrogen bonding interactions on each other in X-ben//pyr...H-F (X = NO(2), CF(3), CN, F, Cl, CH(3) and OH) complexes. The results indicate the cooperativity of interactions in these complexes where face-to-face aromatic interactions and hydrogen bonding interactions coexist. The effects of substituents on the X-ben//pyr...H-F complexes have also been studied with the MP2 method using 6-31G** basis set. The total binding energy increases in both electron-donating and withdrawing substituents. Herein, computational results indicate an enhanced pi-stacking interaction for all substituted complexes related to an unsubstituted case. On the other hand, H...N hydrogen bond interaction is declined by strong electron withdrawing substituents (NO(2) and CN) only. The cooperativity of pi-stacking and H...N hydrogen bond interaction has also been studied by using the atoms in molecules (AIM), natural bond orbital (NBO) and molecular electrostatic potential (MEP) analyses. There are good relationships between the Hammett constants and energy data, geometrical parameters, and the results of population analysis in X-ben//pyr...H-F and X-ben//pyr complexes. The characteristics of interactions are directly related to the electrostatic interaction between the rings.

Syntheses and structural characterization of mononuclear Rh–Cp* and Ir–Cp* complexes with η 6-phenanthrene, η 6-pyrene and η 6-triphenylene

Four novel mononuclear Rh–Cp* and Ir–Cp* complexes with polycyclic aromatic hydrocarbons (PAHs), [M(Cp*)(η 6-PAHs)](BF 4) 2 (M = Rh and Ir; Cp* = η 5-C 5Me 5; PAHs = phenanthrene (phn), pyrene (pyr) and triphenylene (triph)), were prepared by the reactions of the intermediate [M(Cp*)(Me 2CO) 3] 2+ with appreciable PAHs. Their structures were characterized by a single crystal X-ray analysis, 1H, 13C { 1H} NMR and 2D NMR techniques. The X-ray crystallographic studies showed that the [M(Cp*)] 2+ fragment is η 6-coordinated to one terminal benzene ring in each PAH. In particular, it is interesting to note that the partial π/π/π/π interaction was formed in the Ir–pyr complex [Ir(Cp*)(η 6-pyr)](BF 4) 2. The 1D and 2D NMR studies described that the Rh–Cp* and Ir–Cp* complexes with PAHs gave unique 1H and 13C { 1H} NMR spectra with positive coordination shifts (Δ δ( 1H, 13C)) in (CD 3) 2CO at 23 °C, which are likely induced by the local effect and the non-local effect on the coordination of the [M(Cp*)] 2+ fragment to PAHs. The decreasing of the coupling constants ( 3 J H–H) in the η 6-coordinated benzene ring is also induced, with no changes in the uncoordinated benzene rings. The time-course of 1H NMR spectra showed that Rh–Cp* and Ir–Cp* complexes with PAHs are partially dissociated to [M(Cp*)(Me 2CO) 3] 2+ and metal-free PAHs in (CD 3) 2CO at 23 °C. It was demonstrated that their stabilities are in the order of Ir–triph, Ir–phn, Ir–pyr and Rh–triph complexes in (CD 3) 2CO.

Studies for Intramolecular Ring Closure of Amino Vinyl Epoxides. Stereoselective Synthesis of Piperidine and Pyrrolidine Systems.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Studies for Intramolecular Ring Closure of Amino Vinyl Epoxides. Stereoselective Synthesis of Piperidine and Pyrrolidine Systems

Hydroxylated piperidine or pyrrolidine systems are indeed a useful building block for the nucleus present in several major classes of pyrrolizidine, indolizidine, and quinolizidine alkaloids. One most reliable methodology to access those systems is a regioand stereoselective ring closure of epoxides by internal nitrogen nucleophile. According to Baldwin rules, ring closure of epoxides generally proceeds via the favored 5-exo mode rather than the 6-endo mode as shown in Scheme 1. In order to reverse this tendency, the introduction of vinyl group adjacent to epoxide is one of the widely employed methods. In contrast to the numerous reports for the ring closure of vinyl epoxides with the internal oxygen nucleophile, there have been only handful examples in the intramolecular ring closure of vinyl epoxides by nitrogen nucleophiles. Moreover, to our best knowledge, there has been no report for acid-induced ring closure of vinyl epoxides with deactivated nitrogen nucleophiles, e.g. protected by Cbz group. Herein we wish to report our results of the ring closure of a number of vinyl epoxides under acidic conditions and its application to the synthesis of alkaloids. In order to explore the scope of the ring closure of the vinyl epoxides, we synthesized various substrates from the corresponding NCbz protected aminoalcohols as shown in Scheme 2. Swern oxidation of the alcohols 1a-c and subsequent HornerWadsworth-Emmons olefination of aldehydes using LiOH, triethyl 4-phosphonocrotonate, and 4 A-MS furnished the (E,E)-dienoates 2a-c in 73-80% yields. Regioselective epoxidation of 2a-c using mCPBA and Na2HPO4 afforded the desired amino epoxy alkenes 3a-c in 80-93% yields. To obtain the epoxy dibromoalkene 6, Swern oxidation of 1b, followed by Wittig olefination (PPh3=CHCO2Et) afforded the unsaturated ester 4 in 68% overall yield. DIBAL reduction and subsequent epoxidation using mCPBA gave the epoxy alcohol 5 in 68% overall yield, which was oxidized with SO3·pyr complex and subsequent dibromoolefination (CBr4, PPh3) to afford the epoxy dibromoolefin 6 in 55% overall yield. Partial reduction of 7 in the presence of Lindlar catalyst and quinoline furnished the (Z)-olefin 8 in 85% yield, which was then subjected to dephthaloylation using excess NH2NH2 and subsequent Cbz protection reaction to afford 9 in 54% yield. Epoxidation of 9 afforded the epoxy alcohol 10 (81%), which was transformed to the vinyl cis-epoxide 11 by oxidation (SO3·pyr complex) and Wittig olefination (PPh3= CHCO2Et) in 61% yield. Our initial task was to find an active acid system in the intramolecular ring closure (Table 1). Thus, the trans-epoxide 3b was treated with various acids (0.1 eq.), such as ZnCl2, Cu(OTf)2, MgBr2, CuBr2, LiClO4, BF3·OEt2, and camphorsulfonic acid (CSA), in methylene chloride at 0 °C. Cu(OTf)2 gives very little cyclized products (< 5%) and MgBr2 (1 eq.) resulted in undesired side reaction to give trans-γ-bromo-δ-hydroxy-α,β-unsatutrated ester (structure not shown) in 89% yield, which was generated by attack of Scheme 1 Scheme 2. (a) (COCl)2, DMSO, Et3N, -78 °C; (b) (E)-(EtO)2P(O)CH2CH=CHCO2Et, LiOH, 4 A-MS, THF, reflux; (c) mCPBA, Na2HPO4, CH2Cl2, r.t; (d) PPh3=CHCO2Et, benzene, reflux; (e) DIBAL, CH2Cl2, -78 °C; (f) SO3·pyridine, CH2Cl2 : DMSO (4 : 1); (g) PPh3, CBr4, CH2Cl2, 0 °C.

Multiple hematopoietic defects and delayed globin switching in Ikaros null mice.

We have previously reported the structure of a chromatin remodeling complex (PYR complex) with Ikaros as its DNA binding subunit that is specifically present in adult murine and human hematopoietic cells. We now show that homozygous Ikaros "knockout" (null) mice lack the PYR complex, demonstrating the requirement for Ikaros in the formation of the complex on DNA. Heterozygous Ikaros null mice have about half as much PYR complex, indicating a dosage effect for both Ikaros and PYR complex. We also show that Ikaros null mice have multiple hematopoietic cell defects including anemia and megakaryocytic abnormalities, in addition to previously reported lymphoid and stem cell defects. The null mice also have a delay in murine embryonic to adult beta-globin switching and a delay in human gamma to beta switching, consistent with a previously suggested role for PYR complex in this process. Lastly, cDNA array analyses indicate that several hematopoietic cell-specific genes in all blood lineages are either up- or down-regulated in 14-day embryos from Ikaros null as compared with wild-type mice. These results indicate that Ikaros and PYR complex function together in vivo at many adult hematopoietic cell-specific genes and at intergenic sites, affecting their expression and leading to pleiotropic hematopoietic defects.

An ikaros-containing chromatin-remodeling complex in adult-type erythroid cells.

We have previously described a SWI/SNF-related protein complex (PYR complex) that is restricted to definitive (adult-type) hematopoietic cells and that specifically binds DNA sequences containing long stretches of pyrimidines. Deletion of an intergenic DNA-binding site for this complex from a human beta-globin locus construct results in delayed human gamma- to beta-globin switching in transgenic mice, suggesting that the PYR complex acts to facilitate the switch. We now show that PYR complex DNA-binding activity also copurifies with subunits of a second type of chromatin-remodeling complex, nucleosome-remodeling deacetylase (NuRD), that has been shown to have both nucleosome-remodeling and histone deacetylase activities. Gel supershift assays using antibodies to the ATPase-helicase subunit of the NuRD complex, Mi-2 (CHD4), confirm that Mi-2 is a component of the PYR complex. In addition, we show that the hematopoietic cell-restricted zinc finger protein Ikaros copurifies with PYR complex DNA-binding activity and that antibodies to Ikaros also supershift the complex. We also show that NuRD and SWI/SNF components coimmunopurify with each other as well as with Ikaros. Competition gel shift experiments using partially purified PYR complex and recombinant Ikaros protein indicate that Ikaros functions as a DNA-binding subunit of the PYR complex. Our results suggest that Ikaros targets two types of chromatin-remodeling factors-activators (SWI/SNF) and repressors (NuRD)-in a single complex (PYR complex) to the beta-globin locus in adult erythroid cells. At the time of the switch from fetal to adult globin production, the PYR complex is assembled and may function to repress gamma-globin gene expression and facilitate gamma- to beta-globin switching.

Tissue-specific and developmental stage-specific DNA binding by a mammalian SWI/SNF complex associated with human fetal-to-adult globin gene switching

SWI/SNF complexes in yeast and higher eukaryotes are thought to facilitate gene activation and transcription factor binding by disrupting repressive chromatin structures. Little is known, however, about how these complexes target specific genes for activation. We now have purified a specialized SWI/SNF-related complex (PYR complex) from murine erythroleukemia (MEL) cell nuclear extract that binds pyrimidine-rich elements at the human and murine beta-globin loci. PYR complex DNA-binding activity is restricted to definitive hematopoietic cells and is both DNA sequence- and length-dependent. Mass spectrometric identification of purified peptides and antibody supershift assays indicate that PYR complex contains at least four known mammalian SWI/SNF subunits: BAF57, INI1, BAF60a, and BAF170. PYR complex broadly footprints a 250-bp pyrimidine-rich element between the human fetal and adult beta-globin genes. A short intergenic deletion that removes this element from a human globin locus cosmid construct results in delayed human fetal-to-adult globin gene switching in transgenic mice. Taken together, the data suggest that PYR complex may act through this intergenic element to facilitate human fetal-to-adult globin gene switching, presumably by opening the locus in the region of the adult genes to permit the binding of beta-globin transcriptional activators.

Spectroscopic and electrochemical properties of Pt(II) complexes with aromatic terdendate (C^N^C) cyclometallating ligands

Absorption spectra, emission spectra, emission lifetime and electrochemical behavior of the complexes c-Pt(Hdpbhq) 2, t-Pt(dpbhq)S(Et) 2, t-Pt(dpbhq)py, and t-Pt(dpbhq)pyr (where dpbhq 2− is the C − deprotonated form of 5,6-dihydro-2,4-diphenylbenzo(h)quinoline (H 2dpbhq) and py and pyr are pyridine and pyrazine) have been studied. The structured luminescence spectra observed at 77 K have been assigned to transitions having: (i) metal-to-ligand charge transfer (MLCT) character in the case of Pt(H-dpbhq) 2 and mainly MLCT character with some ligand-centered (LC) contribution for the three terdentate trans Pt(II) complexes. The luminescence emission in all cases involves the dpbhq ligand even though the electrochemical results suggest a lowest unoccupied molecular orbital (LUMO) centered on the pyrazine ligand in the Pt(dpbhq)pyr complex.

Spectroscopic properties of Pt(II) and Pd(II) complexes with aromatic terdendate (C″>N^C) cyclometallating ligands

Emission spectra, emission lifetime and electrochemical behavior of the complexes Pt(H-dppy) 2, Pt(dppy)S(Et) 2, Pt(dppy)py, Pt(dppy)pyr, (dppy)Pt-pyr-Pt(dppy), and Pd(dppy)py (where dppy 2− is the C − deprotonated form of 2,6-di-phenylpyridine and py and pyr are pyridine and pyrazine) have been studied. The structured luminescence spectra observed at 77 K have been assigned to transitions having i) MLCT character in the case of Pt(H-dppy) 2, ii) mainly MLCT character with some LC contribution for the four tridentate trans Pt(II) complexes and iii) almost pure LC character for the Pd(II) complex. The luminescence emission involves in all cases the dppy ligand even though the electrochemical results suggest a LUMO orbital centred on the pyrazine ligand in the Pt(dppy)pyr complex and on the metal in the Pd(dppy)py complex.

The lactate dehydrogenase catalyzed pyruvate adduct reaction: simultaneous general acid-base catalysis involving an enzyme and an external catalyst.

The pH dependence of the reaction catalyzed by lactate dehydrogenase, where pyruvate adds covalently to NAD to yield a NAD-Pyr adduct, together with published data on the pH dependence of parameters in the normal redox reaction suggests similar binding modes for enolpyruvate and lactate in their complexes with E X NAD (where E is one-fourth of the tetramer), for ketopyruvate in its complexes with the protonated species, E X H X NAD and E X H X NADH, and for the NAD--Pyr adduct and NADH plus pyruvate in their complexes with E X H. These similarities, together with previous data, suggest a reaction scheme for the formation of the enzyme-adduct complex that includes the relevant proton-transfer steps. Seven different amine chloride buffers were used in a study of the reverse adduct reaction, i.e., the decomposition of E X H X NAD--Pyr. These act with varying efficiencies as external general acid catalysts; the enzyme apparently acts as a (internal) general base. The involvement of the amine chloride buffers as external general catalysts is supported by the concentration dependence of the buffer effect, by a Brönsted plot, and by solvent deuterium isotope effects. The involvement of the enzyme as an internal general catalyst is inferred from the pH dependence of the reaction and the identities of the nearby groups in the E X H X NAD--Pyr complex (from crystallographic studies). The dependence of the adduct reaction on chloride concentration indicates the presence of dead-end inhibitor complexes of E X H X Cl and E X H X NAD X Cl. Chloride also accelerates the decomposition of the adduct in the complex E X H X NAD--Pyr by binding to this complex.