MC Form Research Articles

Evolution of microstructure and 800 °C/294 MPa stress rupture property of cast Ni-based superalloys during long-term thermal exposure: Role and behavior of primary MC carbide

The role and behavior of primary MC carbide and their effects on the microstructure and stress rupture property of the cast Ni-based superalloys during long-term thermal exposure at elevated temperature are systemically investigated in this work. It is found that the chemical compositions of primary MC are proportional to the Nb/Ti and (Ti + Nb)/(Mo + W) ratios of alloys. During long-term thermal exposure, the thermal stability of primary MC can be quantitatively evaluated by its decomposition degree defined as Dt=(V0-Vt)/V0 × 100%, which is closely associated with the Nb/Ti and (Mo + W)/Cr ratios of alloys. The decomposition process, degree, form and mechanism of primary MC are revealed in detail. The STEM observations with the EDS analyses show that primary MC decomposition is an inter-diffusion process of elements between the primary MC carbide and γ matrix, which can increase the volume fraction of γ' phase, restrain the precipitation of topologically close-packed (TCP) phases and promote the coarsening of grain boundaries (GBs). The combination of these microstructural evolutions, together with the appropriate Al + Ti + Nb and W + Mo contents in the matrix, eventually results in a remarkable improvement in the stress rupture property of long-term thermally exposed cast Ni-based superalloys.

Microstructural Changes and Determination of a Continuous Cooling Transformation (CCT) Diagram Using Dilatometric Analysis of M398 High-Alloy Tool Steel Produced by Microclean Powder Metallurgy.

The paper deals with the dilatometric study of high-alloy martensitic tool steel with the designation M398 (BÖHLER), which is produced by the powder metallurgy process. These materials are used to produce screws for injection molding machines in the plastic industry. Increasing the life cycle of these screws leads to significant economic savings. This contribution focuses on creating the CCT diagram of the investigated powder steel in the range of cooling rates from 100 to 0.01 °C/s. JMatPro® API v7.0 simulation software was used to compare the experimentally measured CCT diagram. The measured dilatation curves were confronted with a microstructural analysis, which was evaluated using a scanning electron microscope (SEM). The M398 material contains a large number of carbide particles that occur in the form of M7C3 and MC and are based on Cr and V. EDS analysis was used to evaluate the distribution of selected chemical elements. A comparison of the surface hardness of all samples in relation to the given cooling rates was also carried out. Subsequently, the nanoindentation properties of the formed individual phases as well as the carbides, where the nanohardness and reduced modulus of elasticity (carbides and matrix) were evaluated.

Spiropyran-Based Soft Substrate with SPR, Anti-Reflection and Anti-NRET for Enhanced Visualization/Fluorescence Dual Response to Metal Ions.

The photoluminescence of modified spiropyran on solid surfaces is poor, and the fluorescence intensity of its MC form is weak, which affects its application in the field of sensing. In this work, a PMMA layer containing Au nanoparticles and a spiropyran monomolecular layer are coated on the surface of a PDMS substrate with inverted micro-pyramids successively by means of interface assembly and soft lithography, and the overall structure is similar to insect compound eyes. The anti-reflection effect of the bioinspired structure, the SPR (surface plasmon resonance) effect of the Au nanoparticles and the anti-NRET (non-radiation energy transfer) effect of the PMMA isolation layer raise the fluorescence enhancement factor of the composite substrate vs. the surface MC form of spiropyran to 5.06. In the process of metal ion detection, the composite substrate can achieve both colorimetric and fluorescence response, and the detection limit for Zn2+ can reach 0.281 μM. However, at the same time, the lack of the ability to recognize specific metal ions is expected to be further improved by the modification of spiropyran.

Making microgels photo-responsive by complexation with a spiropyran surfactant.

We report on triggering of p(NIPAM-AA) microgels' photo-responsiveness by making complexes with a spiropyran (SP) containing surfactant. Being dissolved in water, the SP surfactant in its merocyanine state bears three charges, while irradiation with UV and vis light leads to the partial or complete reversal of the SP state. The complexation of the photo-responsive amphiphile with swollen anionic microgels results in charge compensation within the gel interior and as a consequence its size reduces and the volume phase transition temperature (VPTT) decreases down to 32 °C. Under irradiation the MC form photo-isomerizes to a ring closed SP state generating a more hydrophobic surfactant with one positive charge at the head. The increase in the hydrophobicity of the surfactant and thus of the interior of the gel results in the reversible size change of the microgel. We investigate the photo-responsivity of the microgel as a function of wavelength and irradiation intensity, as well as of surfactant concentration and charge density of the microgel. We show that the change in the size and VPTT of the microgels during irradiation occurs through a combination of two processes: heating of the solution during light absorption by the surfactant (more pronounced in the case of UV irradiation) and the change in the hydrophobicity of the surfactant.

Supramolecular assembly of dendronized spiropyrans in aqueous solutions into nanospheres with photo- and thermo-responsive chiralities.

Tailoring the amphiphilicity of a molecule through external stimuli can alter the balance between self-association and repulsion, resulting in different propensities for its assembly. Here we report on the supramolecular assembly of a series of dendronized spiropyrans (DSPs) in water. These DSPs carry 3-fold dendritic oligoethylene glycols (OEGs) with either methoxyl or ethoxyl terminals for different hydrophilicities, and contain an Ala-Gly dipeptide to provide the chirality. These dendronized amphiphiles form supramolecular nanospheres in aqueous solutions with remarkable induced chirality to a level of 1.0 × 106 deg cm2 dmol-1. They can be tuned reversibly through photoisomerization of the spiropyran moieties from the hydrophobic SP form into the hydrophilic MC form, and can even become chirally silent through thermally mediated collapse of the dendritic OEGs. Photoisomerization of the spiropyran moieties in these DSPs is accompanied by simultaneous changes of UV absorption, fluorescence emission, supramolecular chirality and aqueous solution colors. These supramolecular nanospheres exhibit characteristic thermoresponsive behavior due to thermal collapse of the dendritic OEGs with their cloud point temperatures (Tcps) being dependent on the overall hydrophilicity of the molecules and also the aggregate morphologies resulting from how dendritic OEGs are wrapped around the aggregates. Both photo-irradiation-mediated isomerization of the spiropyran moieties and thermally mediated dehydration and collapse of the dendritic OEGs influence the amphiphilicity of these DSPs and their solvation by water, leading to varied driving forces for their assembly. NMR, circular dichroism (CD) and fluorescence spectroscopy techniques, as well as DLS and AFM techniques are combined to follow the supramolecular assembly and illustrate the aggregation mechanism. All experimental results demonstrate that the reversible chirality of the aggregates originates from the balance between dendritic OEGs and spiropyran moieties against water solvation.

Photochemical OFF/ON Cytotoxicity Switching by Using a Photochromic Surfactant with Visible Light Irradiation.

Photochemical switching of cytotoxicity by using spiropyran compounds with pyridinium and alkyl groups was investigated. The spiropyran compound, SP6, with a hexyl group as the alkyl group displayed negative photochromism, in which the hydrophilic open merocyanine form (MC form) was stable and isomerized to the hydrophobic closed spiro form (SP form) by visible light irradiation. Both MC and SP forms exhibited amphiphilicity because of the hydrophobic hexyl and hydrophilic pyridinium groups introduced. Cytotoxicity toward HeLa cells was observed for both MC and SP forms of SP6 at concentrations higher than the critical aggregation concentration of the isomers CACMC and CACSP (CACMC > CACSP), respectively. In contrast, cytotoxicity by SP6 was activated by visible light irradiation at concentrations between CACMC and CACSP; thus, photochemical switching of cytotoxicity from the OFF to ON state was achieved. Cytotoxicity was revealed to be caused by disruption of the cell membrane. The results provide an important step in developing novel next-generation photochemotherapy drugs.

Merocyanines in a Halogen-Bonded Network Involving Inorganic Building Blocks

In this work, we present spiropyran derivatives (SP) involving a halogen bonded network with the addition of inorganic building blocks, i.e. inorganic acids and bivalent metal salts. In solution, a ring-opening isomerization of the spiropyran results in the colored merocyanine isomer (MC), which is only rarely observed in the solid state. By detaining the phenolate oxygen atom of the merocyanine in a hydrogen (HB) or halogen bond (XB) we can successfully obtain this form and access a variation in chromic properties. The O atom of the open MC form unfortunately only represents a weak XB acceptor which led us to introduce supplementary building blocks to strengthen this type of interaction. Fourteen new crystal forms were determined with 3 spiropyran derivatives (1,3,3-trimethylindolinospiropyran (SPH/MCH), 1,3,3-trimethylindolino-6′-nitrobenzopyrylospiran (SPNO2/MCNO2), 1,3,3-trimethylindolino-β-naphthopyrylospiran (SPBenz/MCBenz)) and several di- and tritopic XB donors (1,3,5-triiodotrifluorobenzene (135tfib), 1,4-diiodotetrafluorobenzene (14tfib), 1,3-diiodotetrafluorobenzene (13tfib), 1,2-diiodotetrafluorobenzene (12tfib), abd 1,2-diiodotetrafluoroethan (12tfe)) as well as a polymorphic form of the parent compound with hydrochloric acid. We successfully expanded the XB interaction possibilities with hydrochloric acid or zinc/cobalt chloride and found proof of the tunability of the chromic properties in the solid state using these building blocks.

Light-, temperature-, and pH-responsive micellar assemblies of spiropyran-initiated amphiphilic block copolymers: Kinetics of photochromism, responsiveness, and smart drug delivery.

Multi-responsive polymer assemblies are a significant class of smart polymers with potential applications in drug-delivery and gen-delivery systems. Poly(dimethylaminoethyl methacrylate) (PDMAEMA) is among the most applicable multi-responsive polymers that changes its physical and chemical properties in response to temperature, pH, and CO2. Herein, different types of light-, temperature-, pH-, and CO2-responsive polymer assemblies were developed based on multi-responsive PDMAEMA and hydrophobic poly(methyl methacrylate) blocks. In addition, spiropyran was incorporated at the chain ends by using spiropyran-initiated atom transfer radical polymerization method. Novel smart drug-delivery systems were developed by self-assembly of these amphiphilic block copolymers to micellar morphologies in aqueous media. Dynamic light scattering results showed that size of the polymer assemblies changed in response to pH variations (from 5 to 9), temperature changes (above the lower critical solution temperature (LCST) of PDMAEMA), and also UV light irradiation (wavelength of 365nm). The LCST of PPDMAEMA showed a shift from 53 to 60°C after isomerization of the SP to MC form, as a result of increase of polarity and water-solubility. The PDMAEMA block results in responsivity of the prepared copolymer assemblies to CO2, which display pH variation from 8-8.6 to 5-6 after 2min of CO2 gas bubbling. All the multi-responsive micellar polymer assemblies showed various loading capacities and release profiles, and the DOX release can be controlled by pH, temperature, and light. The release efficiency is reached to 60-85% at pH5.3, 80-90% at temperatures higher than the LCST of PDMAEMA (60°C), and also 90-100% under UV light irradiation after 48h. In summary, the multi-responsive polymer assemblies based on amphiphilic block copolymers containing spiropyran chain end groups in the current study have potential applications in smart drug-delivery systems, and offer controlling over the drug-release by different triggers, such as light irradiation, pH variation, and temperature change. A very low concentration of spiropyran molecules (one per polymer chain) showed light-controlling of drug-release from the assemblies with high efficiencies.

ON THE INFLUENCE OF THE POROSITY OF FINE-GRAINED CONCRETES AND DRY BUILDING MIXTURES ON CONTACT ZONE FROST RESISTANCE

ObjectivesThis study was aimed at identifying the dependency of the frost resistance of the contact zone of fine-grained concretes (FGCs) obtained from dry building mixtures (DBMs) based on various Portland cements (PCs) with the content of various redispersable polymer powders (RPPs) from 0 to 3%.MethodThe research was based on 75 freeze-defrost cycles.ResultsAlthough the average dependency of adhesion with the base on additional porosity after 75 freeze-defrost cycles does not depend on the nature of NMV, adhesion is influenced by the cement type, the type and dosage of RPPs, as well as the nature of additional porosity. Since the content of organised volume of NMV in the form of VV has no effect on changes in adhesion with the concrete base following 75 freeze-defrost cycles, it is impractical to add more than 7% of NMV in the form of MS to the concrete mixture. The feasibility of using sulphate-resistant cement requires more research. The practical RPP dosage should be 1-2%. Some contradictions in conclusions on the volume of the introduced MS (by the strength criterion – at least 6%, by the criterion of frost resistance of the contact zone – no more than 7%) allows us to recommend the dosage of MS in RPP within 6-7% by volume for obtaining additional data on the MS effect on frost resistance.ConclusionThe dependency of compressive strength on additional porosity for FGCs without NMV and with NMV in the VV form after hardening during 28 days under normal conditions almost coincides with the known dependency of strength on porosity for cement stone; the maximum divergence of the values ???????? ????0 in the investigated range does not exceed 5%. The dependency of compressive strength on additional porosity for FGCs without NMV and with NMV in the MS form is similar to the known dependency of strength from porosity for cement stone; however, with increasing porosity, there is a slight decrease in the effect of porosity on strength. The dependency of compressive strength after 75 freeze-defrost cycles on additional porosity for FGC without NMV practically coincides with the previously obtained dependency of strength on porosity for cement stone; the maximum divergence of the values ???????? ????0 in the investigated range does not exceed 9%. For FGCs with NMV in the MC form, increasing porosity causes a slight decrease in the porosity effect on strength, and for FGCs with NMV in the VV form, the dependency has a quantitative and qualitative difference. The value of NMV in the VV form recommended for improving the frost resistance of FGCs by the strength criterion is at least 3%, MS – at least 6%. According to the criterion of the frost resistance of the contact zone and the strength of MS, the recommended dosage is 6-7%. It was not possible to disclose the direct impact of the VV volume on the frost resistance of the contact zone.

Maintenance DNA Methyltransferase Activity in the Presence of Oxidized Forms of 5-Methylcytosine: Structural Basis for Ten Eleven Translocation-Mediated DNA Demethylation.

A precise balance of DNA methylation and demethylation is required for epigenetic control of cell identity, development, and growth. DNA methylation marks are introduced by de novo DNA methyltransferases DNMT3a/b and are maintained throughout cell divisions by DNA methyltransferase 1 (DNMT1), which adds methyl groups to hemimethylated CpG dinucleotides generated during DNA replication. Ten eleven translocation (TET) dioxygenases oxidize 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), and 5-carboxylcytosine (caC), a process known to induce DNA demethylation and gene reactivation. In this study, we investigated the catalytic activity of human DNMT1 in the presence of oxidized forms of mC. A mass spectrometry-based assay was employed to study the kinetics of DNMT1-mediated cytosine methylation in CG dinucleotides containing C, mC, hmC, fC, or caC across from the target cytosine. Homology modeling, coupled with molecular dynamics simulations, was used to explore the structural consequences of mC oxidation with regard to the geometry of protein-DNA complexes. The DNMT1 enzymatic activity was strongly affected by the oxidation status of mC, with the catalytic efficiency decreasing in the following order: mC > hmC > fC > caC. Molecular dynamics simulations revealed that DNMT1 forms an unproductive complex with DNA duplexes containing oxidized forms of mC as a consequence of altered interactions of the target recognition domain of the protein with the C-5 substituent on cytosine. Our results provide new structural and mechanistic insight into TET-mediated DNA demethylation.

Substituent effects on the photochromic properties of 3,3-diphenyspiro[benzofluorenopyran-cyclopentaphenanthrene

The introduction of electron-donating groups on the skeleton of a naphthopyran, 3,3-diphenyspiro[benzofluorenopyran-cyclopentaphenanthrene], has led to the development of a photochromic dye applicable to photochromic lenses. Introducing a methoxy group to C6 moved the absorption band of the MC form towards the longer wavelength. Further introduction of methoxy groups to the para-position of the phenyl groups on C3 induced faster decoloration of the MC form. Additional introduction of a methoxy group to C13 led to the enhancement of the absorption intensity as well as the facile, economic synthesis of the dye caused by the symmetrical property of the starting material.

Effects of Carbon Content on Mechanical Properties of Inconel 718 Alloy

For improving the service performance of Inconel 718 alloy, especially used as a corrosion-resistant alloy for special environment, the microstructure and mechanical property of different carbon-containing Inconel 718 alloys were investigated by the Thermo-Calc software and experiments. The experimental results indicated that the morphology, distribution and types of carbides mainly existing in the form of MC were hardly influenced by solution treatment at 1050 °C for 1 h. The precipitation amount and particle size of carbides decreased with the decrease of carbon content, which was the main reason resulting in the increase of ductility and toughness. In addition, moving dislocation could be restrained by the precipitation of carbides. Therefore, the strength could benefit from the precipitation strengthening of carbides when the precipitation of γ′/γ″ phase was not influenced by the precipitation of carbides.

Photoelectric conversion based on proton-coupled electron transfer reactions.

Making efficient use of solar energy is one of the biggest challenges of our time. In nature, solar energy can be harvested by photosynthesis where proton-coupled electron transfer (PCET) plays a critical role. Here, PCET is utilized for the first time to directly convert light energy to electrical energy. Quinone/hydroquinone PCET redox couples were used to produce a photovoltage along with spiropyrans, photoswitchable compounds that undergo reversible transformation between a ring-closed (Sp) and ring-opened form (Mc). The Mc form is more basic than the Sp form, and the open-circuit voltage (V(oc)) is related to the proton concentration and that of the Sp/Mc ratio controlled by light. V(oc) values from 100 to 140 mV were produced. In addition to direct current (J(sc) ca. 9 μA cm(-2)), alternating current in the range of 0.1 to 200 Hz was also produced by manipulating the input light.

E2-mediated Small Ubiquitin-like Modifier (SUMO) Modification of Thymine DNA Glycosylase Is Efficient but Not Selective for the Enzyme-Product Complex

Thymine DNA glycosylase (TDG) initiates the repair of G·T mismatches that arise by deamination of 5-methylcytosine (mC), and it excises 5-formylcytosine and 5-carboxylcytosine, oxidized forms of mC. TDG functions in active DNA demethylation and is essential for embryonic development. TDG forms a tight enzyme-product complex with abasic DNA, which severely impedes enzymatic turnover. Modification of TDG by small ubiquitin-like modifier (SUMO) proteins weakens its binding to abasic DNA. It was proposed that sumoylation of product-bound TDG regulates product release, with SUMO conjugation and deconjugation needed for each catalytic cycle, but this model remains unsubstantiated. We examined the efficiency and specificity of TDG sumoylation using in vitro assays with purified E1 and E2 enzymes, finding that TDG is modified efficiently by SUMO-1 and SUMO-2. Remarkably, we observed similar modification rates for free TDG and TDG bound to abasic or undamaged DNA. To examine the conjugation step directly, we determined modification rates (kobs) using preformed E2∼SUMO-1 thioester. The hyperbolic dependence of kobs on TDG concentration gives kmax = 1.6 min(-1) and K1/2 = 0.55 μM, suggesting that E2∼SUMO-1 has higher affinity for TDG than for the SUMO targets RanGAP1 and p53 (peptide). Whereas sumoylation substantially weakens TDG binding to DNA, TDG∼SUMO-1 still binds relatively tightly to AP-DNA (Kd ∼50 nM). Although E2∼SUMO-1 exhibits no specificity for product-bound TDG, the relatively high conjugation efficiency raises the possibility that E2-mediated sumoylation could stimulate product release in vivo. This and other implications for the biological role and mechanism of TDG sumoylation are discussed.

Mapping the fluorescence performance of a photochromic-fluorescent system coupled with gold nanoparticles at the single-molecule-single-particle level.

Single-molecule (SM) fluorescence microscopy was used to investigate the photochromic fluorescent system spiropyran-merocyanine (SP ↔ MC) interacting with gold nanoparticles (AuNPs). We observe a significant increase in the brightness of the emissive MC form, in the duration of its ON time, and in the total number of emitted photons. The spatial distribution of SMs with improved photophysical performance was obtained with 40 nm precision relative to the nearest AuNP. We demonstrate that even photochromic systems with poor photochemical performance for SM can become suitable for long time monitoring and high performance microscopy by interaction with metallic NP.

UV light induced plasticization and light activated shape memory of spiropyran doped ethylene-vinyl acetate copolymers

Light activated shape memory polymers (LASMPs) are relatively new kinds of smart materials and have significant technological applications ranging from biomedical devices to aerospace technology. EVA films doped with spiropyran with contents ranging from 0.1% to 3% show efficient UV activated shape memory behaviors if the fixed shape deformation is limited within 80%. For EVA films containing 3% spiropyran, UV irradiation causes a decrease in EVA modulus of about 44%. FT-IR and solid (13)C NMR in association with UV-vis absorption analysis demonstrate that UV irradiation transforms spiropyran from the SP form to the MC form, meanwhile, it induces an increase in the molecular mobility in the amorphous phase of EVA. Thus, the spiropyran-doped EVA films act as LASMPs via a mechanism of light induced plasticization. Light activated spiropyran acts as a plasticizer to EVA.

TDG excision of fC may be a predominant element of pathways for active DNA demethylation

Base excision repair (BER) is essential for maintaining genetic integrity and for active DNA demethylation, a central element of epigenetic gene regulation. A key player in both processes is thymine DNA glycosylase (TDG), which excises modified forms of 5‐methylcytosine (mC). TDG excises thymine from mutagenic G/T mispairs arising from mC deamination. TDG also excises 5‐formylcytosine (fC) and 5‐carboxylcytosine (caC), oxidized forms of mC generated by Tet enzymes. TDG is essential for embryonic development, reflecting a crucial function in regulating gene expression that likely involves a key step in active DNA demethylation. We used structural, biochemical, and cell‐based methods to understand how TDG attains specificity for excising select forms of modified mC (i.e., T, fC, and caC). We identified a TDG variant that retains fC activity, but lacks detectible caC activity, indicating a fundamental difference in the excision mechanism for these related bases. We used this variant to study the role of TDG in active DNA demethylation in human cells. The results indicate that TDG excision of fC can account for findings that caC is depleted in cells expressing TDG, consistent with the fact that fC is a precursor for Tet‐mediated formation of caC. The results suggest that TDG excision of fC could be a predominant element in a pathway for active DNA demethylation. Supported by the NIH (R01‐GM072711).

UV/Vis and NIR Light-Responsive Spiropyran Self-Assembled Monolayers

Self-assembled monolayers of a 6-nitro BIPS spiropyran (SP) modified with a disulfide-terminated aliphatic chain were prepared on polycrystalline gold surfaces and characterized by UV/vis absorption, surface-enhanced Raman scattering (SERS), and X-ray photoelectron spectroscopies (XPS). The SAMs obtained are composed of the ring-closed form (i.e., spiropyran) only. Irradiation with UV light results in conversion of the monolayer to the merocyanine form (MC), manifested in the appearance of an N(+) contribution in the N 1s region of the XPS spectrum of the SAMs, the characteristic absorption band of the MC form in the visible region at 555 nm, and the C-O stretching band in the SERS spectrum. Recovery of the initial state of the monolayer was observed both thermally and after irradiation with visible light. Several switching cycles were performed and monitored by SERS spectroscopy, demonstrating the stability of the SAMs during repeated switching between SP and MC states. A key finding in the present study is that ring-opening of the surface-immobilized spiropyrans can be induced by irradiation with continuous wave NIR (785 nm) light as well as by irradiation with UV light. We demonstrate that ring-opening by irradiation at 785 nm proceeds by a two-photon absorption pathway both in the SAMs and in the solid state. Hence, spiropyran SAMs on gold can undergo reversible photochemical switching from the SP to the MC form with both UV and NIR and the reverse reaction induced by irradiation with visible light or heating. Furthermore, the observation of NIR-induced switching with a continuous wave source holds important consequences in the study of photochromic switches on surfaces using SERS and emphasizes the importance of the use of multiple complementary techniques in characterizing photoresponsive SAMs.

Reversibly Light-Modulated Dirac Point of Graphene Functionalized with Spiropyran

Graphene has been functionalized with spiropyran (SP), a well-known photochromic molecule. It has been realized with pyrene-modified SP, which has been adsorbed on graphene by π-π interaction between pyrene and graphene. The field-effect transistor (FET) with SP-functionalized graphene exhibited n-doping effect and interesting optoelectronic behaviors. The Dirac point of graphene in the FET could be controlled by light modulation because spiropyran can be reversibly switched between two different conformations, a neutral form (colorless SP) and a charge-separated form (purple colored merocyanine, MC), on UV and visible light irradiation. The MC form is produced during UV light irradiation, inducing the shift of the Dirac point of graphene toward negative gate voltage. The reverse process back to the neutral SP form occurred under visible light irradiation or in darkness, inducing a shift of the Dirac point toward positive gate voltage. The change of the Dirac point by UV and visible light was reproducibly repeated. SP molecules also improved the conductance change in the FET device. Furthermore, dynamics on conversion from MC to SP on graphene was different from that in solution and solid samples with SP-grafted polymer or that on gold nanoparticles.

Lesion processing by a repair enzyme is severely curtailed by residues needed to prevent aberrant activity on undamaged DNA

DNA base excision repair is essential for maintaining genomic integrity and for active DNA demethylation, a central element of epigenetic regulation. A key player is thymine DNA glycosylase (TDG), which excises thymine from mutagenic G·T mispairs that arise by deamination of 5-methylcytosine (mC). TDG also removes 5-formylcytosine and 5-carboxylcytosine, oxidized forms of mC produced by Tet enzymes. Recent studies show that the glycosylase activity of TDG is essential for active DNA demethylation and for embryonic development. Our understanding of how repair enzymes excise modified bases without acting on undamaged DNA remains incomplete, particularly for mismatch glycosylases such as TDG. We solved a crystal structure of TDG (catalytic domain) bound to a substrate analog and characterized active-site residues by mutagenesis, kinetics, and molecular dynamics simulations. The studies reveal how TDG binds and positions the nucleophile (water) and uncover a previously unrecognized catalytic residue (Thr197). Remarkably, mutation of two active-site residues (Ala145 and His151) causes a dramatic enhancement in G·T glycosylase activity but confers even greater increases in the aberrant removal of thymine from normal A·T base pairs. The strict conservation of these residues may reflect a mechanism used to strike a tolerable balance between the requirement for efficient repair of G·T lesions and the need to minimize aberrant action on undamaged DNA, which can be mutagenic and cytotoxic. Such a compromise in G·T activity can account in part for the relatively weak G·T activity of TDG, a trait that could potentially contribute to the hypermutability of CpG sites in cancer and genetic disease.