Our understanding of oxidative damage to double helical DNA and the design of DNA-based devices for molecular electronics is crucially dependent upon elucidation of the mechanism and dynamics of electron and hole transport in DNA. Electrons and holes can migrate from the locus of formation to trap sites, and such migration can occur through either a single-step "superexchange" mechanism or a multistep charge transport "hopping" mechanism. The rates of single-step charge separation and charge recombination processes are found to decrease rapidly with increasing transfer distances, whereas multistep hole transport processes are only weakly distance dependent. However, the dynamics of hole transport has not yet been directly determined. Here we report spectroscopic measurements of photoinduced electron transfer in synthetic DNA that yield rate constants of approximately 5 x 10(7) s(-1) and 5 x 10(6) s(-1), respectively, for the forward and return hole transport from a single guanine base to a double guanine base step across a single adenine. These rates are faster than processes leading to strand cleavage, such as the reaction of guanine cation radical with water, thus permitting holes to migrate over long distances in DNA. However, they are too slow to compete with charge recombination in contact ion pairs, a process which protects DNA from photochemical damage.

The driving force dependence of photoinduced electron-transfer dynamics in duplex DNA has been investigated for 16 synthetic DNA hairpins in which an acceptor chromophore serves as a linker connecting two complementary oligonucleotide arms containing a single donor nucleobase located either adjacent to the linker or separated from the linker by two unreactive base pairs. The rate constants for both charge separation and charge recombination processes have been determined by means of subpicosecond time-resolved transient absorption spectroscopy and the results analyzed using quantum mechanical Marcus theory. This analysis provides intimate details about electron-transfer processes in DNA including the distance dependence of the electronic coupling between the acceptor and nucleobase donor and the solvent and nuclear reorganization energies.

Gliomas are the most common primary brain tumors in children and adults. We recently identified frequent alterations in chromatin remodelling pathways including recurrent mutations in H3F3A and mutations in ATRX (α-thalassemia/mental-retardation-syndrome-X-linked) in pediatric and young adult glioblastoma (GBM, WHO grade IV astrocytoma). H3F3A mutations were specific to pediatric high-grade gliomas and identified in only 3.4 % of adult GBM. Using sequencing and/or immunohistochemical analyses, we investigated ATRX alterations (mutation/loss of expression) and their association with TP53 and IDH1 or IDH2 mutations in 140 adult WHO grade II, III and IV gliomas, 17 pediatric WHO grade II and III astrocytomas and 34 pilocytic astrocytomas. In adults, ATRX aberrations were detected in 33 % of grade II and 46 % of grade III gliomas, as well as in 80 % of secondary and 7 % of primary GBMs. They were absent in the 17 grade II and III astrocytomas in children, and the 34 pilocytic astrocytomas. ATRX alterations closely overlapped with mutations in IDH1/2 (p < 0.0001) and TP53 (p < 0.0001) in samples across all WHO grades. They were prevalent in astrocytomas and oligoastrocytomas, but were absent in oligodendrogliomas (p < 0.0001). No significant association of ATRX mutation/loss of expression and alternative lengthening of telomeres was identified in our cohort. In summary, our data show that ATRX alterations are frequent in adult diffuse gliomas and are specific to astrocytic tumors carrying IDH1/2 and TP53 mutations. Combined alteration of these genes may contribute to drive the neoplastic growth in a major subset of diffuse astrocytomas in adults.

The dynamics of photoinduced charge separation and charge recombination in synthetic DNA hairpins have been investigated by means of femtosecond and nanosecond transient spectroscopy. The hairpins consist of a stilbene linker connecting two complementary 6-mer or 7-mer oligonucleotide strands. Base pairing between these strands results in formation of hairpins in which the stilbene is approximately parallel to the adjacent base pair. The singlet stilbene is selectively quenched by guanine, but not by the other nucleobases, via an electron-transfer mechanism in which the stilbene singlet state is the electron acceptor and guanine is the electron donor. In a hairpin containing only A:T base pairs, no quenching occurs and the restricted geometry results in a long stilbene lifetime and high fluorescence quantum yield. In families of hairpins which contain a single G:C base pair at varying locations in the hairpin stem, the stilbene fluorescence lifetime and quantum yield decrease as the stilbene-guanine distance decreases. Transient absorption spectroscopy is used to monitor the disappearance of the stilbene singlet and the formation and decay of the stilbene anion radical. Analysis of these data provides the rate constants for charge separation and charge recombination. Both processes show an exponential decrease in rate constant with increasing stilbene-guanine distance. Thus, electron transfer is concluded to occur via a single-step superexchange mechanism with a distance dependence β ) 0.7 Å -1 for charge separation and 0.9 Å -1 for charge recombination. The rate constants for charge separation and charge recombination via polyA vs polyT strands are remarkably similar, slightly larger values being observed for polyA strands. The dynamics of electron transfer in hairpins containing two adjacent G:C base pairs have also been investigated. When the guanines are in different strands, the second guanine has little effect on the efficiency or dynamics of electron transfer. However, when the guanines are in the same strand, somewhat faster charge separation and slower charge recombination are observed than in the case of hairpins with a single G:C base pair. Thus, the GG step functions as a shallow hole trap. The relationship of these results to other theoretical and experimental studies of electron transfer in DNA is discussed.

(6), PPh 3 (7), P(OEt) 3 (8)] were prepared as Fe-only hydrogenase-active-site models by controllable CO displacement of [(μ-pdt)Fe 2 (CO) 6 ] by tertiary phosphanes. The coordination configurations of 3-6 were characterized by X-ray crystallography. Disubstituted diiron complex 6 features an

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