Detection of Methoxymethanol as a Photochemistry Product of Condensed Methanol

We report the identification of methoxymethanol (CH3OCH2OH) as a photochemistry product of condensed methanol (CH3OH) based on temperature-programmed desorption studies conducted following photon irradiation at energies below the ionization threshold (9.8 eV) of condensed methanol. The first detection of methoxymethanol in the interstellar medium was reported in 2017 based on data from Bands 6 and 7 from the Atacama Large Millimeter/submillimeter Array (ALMA). The cosmic synthesis of “complex” organic molecules such as methyl formate (HCOOCH3), dimethyl ether (CH3OCH3), acetic acid (CH3COOH), ethylene glycol (HOCH2CH2OH), and glycolaldehyde (HOCH2CHO) has been attributed to UV photolysis of condensed methanol found in interstellar ices. Experiments conducted in 1995 demonstrated that electron-induced radiolysis of methanol cosmic ice analogues yields methoxymethanol. In three recent publications (2016, 2017, and 2018), methoxymethanol was considered as a potential tracer for reactions induced by secondary electrons resulting from the interaction of cosmic rays with interstellar ices. However, the results presented in this study suggest that methoxymethanol can be formed from both radiation chemistry and photochemistry of condensed methanol

Condensed-Phase Photochemistry in the Absence of Radiation Chemistry

We report post-irradiation photochemistry studies of condensed ammonia using photons of energies below condensed ammonia’s ionization threshold of ~ 9 eV. Hydrazine (N2H4), diazene (also known as diimide and diimine) (N2H2), triazane (N3H5), and one or more isomers of N3H3 are detected as photochemistry products during temperature-programmed desorption. Product yields increase monotonically with (1) photon fluence and (2) film thickness. In the studies reported herein, the energies of photons responsible for product formation are constrained to less than 7.4 eV. Previous post-irradiation photochemistry studies of condensed ammonia employed photons sufficiently energetic to ionize condensed ammonia and initiate radiation chemistry. Such studies typically involve ion-molecule reactions and electron-induced reactions in addition to photochemistry. Although photochemistry is cited as a dominant mechanism for the synthesis of prebiotic molecules in interstellar ices, to the best of our knowledge, ours is one of the first astrochemically-relevant studies that has found unambiguous evidence for condensed-phase chemical synthesis induced by photons in the absence of ionization

Compact zinc finger base editors that edit mitochondrial or nuclear DNA in vitro and in vivo.

DddA-derived cytosine base editors (DdCBEs) use programmable DNA-binding TALE repeat arrays, rather than CRISPR proteins, a split double-stranded DNA cytidine deaminase (DddA), and a uracil glycosylase inhibitor to mediate C•G-to-T•A editing in nuclear and organelle DNA. Here we report the development of zinc finger DdCBEs (ZF-DdCBEs) and the improvement of their editing performance through engineering their architectures, defining improved ZF scaffolds, and installing DddA activity-enhancing mutations. We engineer variants with improved DNA specificity by integrating four strategies to reduce off-target editing. We use optimized ZF-DdCBEs to install or correct disease-associated mutations in mitochondria and in the nucleus. Leveraging their small size, we use a single AAV9 to deliver into heart, liver, and skeletal muscle in post-natal mice ZF-DdCBEs that efficiently install disease-associated mutations. While off-target editing of ZF-DdCBEs is likely too high for therapeutic applications, these findings demonstrate a compact, all-protein base editing research tool for precise editing of organelle or nuclear DNA without double-strand DNA breaks