Amitava Adhikary

1. Ionizing radiation (IR) is a well-established carcinogenic agent capable of inducing both genetic and epigenetic alterations that contribute to malignant transformation (Becker et al. 2007; 2010...

In this work, we have studied the effect of base-pairing on the shape resonances of guanine and cytosine nucleobases. Among the seven π* resonances we identified in the guanine–cytosine (GC) anion radical, three were centered on cytosine, and the remaining were guanine-centered. Relative to the isolated bases, upon base pair formation, the cytosine resonances were redshifted, while the guanine-centered states showed an opposite trend—where their energy was blue shifted. In addition to electronic interactions, geometric distortion and basis-set superposition error also play crucial roles in the resonance positions and widths of the GC radical anion. The electronic interaction from the complementary base seems to have a larger effect on the stabilization of the anionic resonances than the surrounding environment.

In this work, we investigate the effect of an amino acid environment on nucleobase-centered anion radical shape resonances, using uracil as a model system for pyrimidine bases in RNA. Anionic uracil–glycine complexes were used to model the RNA–protein interactions. The resonance positions and widths of these complexes were simulated using the equation of motion coupled cluster method coupled with resonance via the Padé approach. Our results show that in the transient negative ion (TNI, i.e., the anion radical of glycine:uracil complex), glycine stabilizes nucleobase-centered resonances through hydrogen bonding, thereby increasing the lifetime of TNI. Simultaneously, a glycine-centered resonance demonstrates the ability of amino acids to capture the electron density and divert it away from the uracil nucleobase. At the micro-solvation level, this modeling indicates that amino acids would have more influence on nucleobase-centered resonances in the TNI than that displayed by the corresponding aqueous environment.

Azido(N₃)-nucleosides are known for their antiviral and anticancer properties. Recently, N₃-nucleosides have attracted attention for augmenting radiation damage in tumor cells via dissociative electron attachment (DEA) reactions mediated by the simplest and the most potent reducing species (the electron). To investigate the effect of N₃ group substitution at specific sites of the pyrimidine base-ring (C4, C5, and C6) on the DEA reaction, we employed both commercially available and in-house-synthesized N₃-nucleosides. We conducted a comprehensive study combining electron paramagnetic resonance (EPR) spectroscopy at a low temperature, picosecond pulse radiolysis in an aqueous solution under ambient conditions, and DFT calculations. For N₃ substitution at C4, EPR studies and DFT calculations established a stable azide anion radical (R-N₃^•-) formation, after the addition of radiation-produced electrons. For N₃ substitution at C5, the DEA leads to a π-type aminyl radical (R-NH^•) formation. For N₃ substitution at C6, a conjugated iminyl σ-radical (R═N^•) is formed via DEA. R═N^• is in equilibrium with R-NH^•. Thus, this work reports a significant finding: the stabilization and reactivity of each type of nitrogen-centered radical (RN₃^•-, RNH^•, R═N^•) are determined by the position of N₃ substitution on the pyrimidine base-ring.

The cellular environment plays a significant role in low energy electron‐mediated radiation damage to genetic materials. In this study, we have modeled the effect of the bulk medium on electron attachment to nucleobases in diethylene glycol (DEG) using uracil as a test case, in accordance with recent experimental work on the observation of dissociative quasi‐free electron attachment to nucleoside via excited anion radical in solution (in DEG). Our EOM‐CCSD‐based quantum mechanical/molecular mechanical (QM/MM) simulations indicate that the electron scavenging by uracil in DEG is much slower than that observed in the aqueous medium due to its viscosity. This work also establishes that a doorway mechanism exists in uracil microsolvated and bulk solvated with DEG, with the dipole‐bound state and solvent‐bound state acting as doorway states, respectively.

Dose rate is one of the important parameters in radiation-induced biomolecular damage. The effects of dose rate have been known to modify radiation toxicity in biological systems. The rate and extent of sublethal DNA damage (e.g., base damage and single-strand breaks) repair and those of cell proliferation have been manifested by dose rate. However, the recent preclinical application of ultrahigh dose rate [(UHDR) ca. 40 Gy/s and higher] radiation modalities have been shown to lower the type and extent of radiation damage to biological systems. At these UHDR, radiation-induced physicochemical and chemical processes are expected to differ from those observed after irradiation at conventional dose rates (CONV). It is unclear whether these UHDR conditions can affect the quality (type) and quantity (extent) of biomolecular damage such as DNA lesions. Here, we comparatively study the influence of indirect effects of CONV and UHDR on the formation of DNA strand breaks and clustered damage including densely accumulated lesions in an aerated and an anoxic dilute aqueous solution of a plasmid DNA model under low and high hydroxyl radical (•OH) scavenging conditions. Aqueous solutions of purified supercoiled plasmid DNA (pUC19) were prepared in either air- or nitrogen-saturated conditions, with Tris buffer added as the radiation-produced •OH scavenger at low and high scavenging capacities. These DNA samples were irradiated using kV X-ray systems at CONV (0.1 Gy/s) and high dose rate (HDR, 25 Gy/s) as well as UHDR (55 and 125 Gy/s) under different scavenging and environmental conditions. DNA lesions including strand breaks and clustered damage including densely accumulated lesions were quantified by gel electrophoresis and the yields of these lesions were calculated from the dose-response curve. Non-DSB clustered damage including densely accumulated lesions were evaluated by treating DNAs using bacterial endonuclease enzymes (Fpg and Nth) prior to gel electrophoresis. UHDR of 55 and 125 Gy/s induced lower amounts of both isolated strand breaks and clustered DNA damage including densely accumulated lesions at doses >40 Gy in the presence of oxygen, compared to the abundance of these lesions induced by 0.1 and 25 Gy/s irradiation under the same dose conditions. Overall, the strand break and clustered damage including densely accumulated lesions yields decreased by factors of 1.3–3.5 after UHDR. We did not observe these differences either via •OH scavenging or by removing oxygen from the solution. In addition, our results point out that the inter-track recombination reactions did not contribute to the observed dose-rate effects on DNA damage. The effects of dose rate on DNA damage are highly dependent on the total dose, as expected, but also on the •OH scavenging capacity that is employed in the aqueous DNA solutions. These important variables may be relevant in biological systems as well. On a practical level, our in vitro plasmid DNA model, which permits to precisely vary the •OH scavenging capacity and gassing conditions (air saturated vs. N2 saturated) can help to differentiate dose-rate effects on biomolecular damage. Our results indicate that the radical-radical reactions are important in understanding the dose-rate effect on DNA damage.

Produced waters are often treated in open lagoons where hydrogen sulfide (H₂S) can off gas, posing a risk to human health and the environment. The aim of this study was to optimize a treatment process using hydrogen peroxide (H₂O₂) to oxidize H₂S while minimizing off gassing. Samples of produced water from West Texas and laboratory-prepared waters utilizing sodium sulfide (Na₂S) or biogenic polysulfides were oxidized with H₂O₂ alone or in combination with copper or iron catalysts, sodium hydroxide (NaOH), or a commercial sulfide oxidizer, HydroPower Green™. Sulfur speciation was measured using Hach test kits for sulfide/sulfate/sulfite and Dräger tubes for headspace H₂S. HydroPower Green™ (HPG) helped to reduce H₂S in the headspace of water samples; some of this was pH related as NaOH also worked, but not as well as HPG. The dose of peroxide necessary to oxidize sulfides to sulfate is a function of the oxidation-reduction potential (Eh) of the water and total sulfide concentration as well as pH; approximately a 1–4:1 ratio of peroxide to sulfide concentration was needed to oxidize sulfidic waters of pH 7–10 with half-lives under 30 min. Both copper and iron catalysts reduce H₂O₂ demand and the half-life of H₂S. Peracetic acid (PAA) and copper (II) sulfate pentahydrate (CuSO₄, 5H₂O) were explored as biocides for controlling sulfate-reducing bacteria (SRBs) that produce H₂S. An AquaSnap (Hygenia) test kit was employed to monitor relative microbial activity in a wetland porewater containing H₂S. Microbial regrowth occurred after a few days using the highest dose of PAA; these results showed that PAA was being used by bacteria as a carbon source even after the initial substantial reduction in the microbial activity. CuSO₄, 5H₂O at a dose of 1 ppm prevented microbial regrowth. The recommended treatment process from this research is determined by jar testing with H₂O₂, a base for pH control, a biocide, and possibly a metal catalyst or other co-oxidants in order to achieve oxidation of sulfides without H₂S release or the precipitation of metal carbonates or oxides.

Azido-modified nucleosides have been extensively explored as substrates for click chemistry and the metabolic labeling of DNA and RNA. These compounds are also of interest as precursors for further synthetic elaboration and as therapeutic agents. This review discusses the chemistry of azidonucleosides related to the generation of nitrogen-centered radicals (NCRs) from the azido groups that are selectively inserted into the nucleoside frame along with the subsequent chemistry and biological implications of NCRs. For instance, the critical role of the sulfinylimine radical generated during inhibition of ribonucleotide reductases by 2′-azido-2′-deoxy pyrimidine nucleotides as well as the NCRs generated from azidonucleosides by radiation-produced (prehydrated and aqueous) electrons are discussed. Regio and stereoselectivity of incorporation of an azido group (“radical arm”) into the frame of nucleoside and selective generation of NCRs under reductive conditions, which often produce the same radical species that are observed upon ionization events due to radiation and/or other oxidative conditions that are emphasized. NCRs generated from nucleoside-modified precursors other than azidonucleosides are also discussed but only with the direct relation to the same/similar NCRs derived from azidonucleosides.