Electron Attachment Studies with the Potential Radiosensitizer 2-Nitrofuran

Abstract

Nitrofurans belong to the class of drugs typically used as antibiotics or antimicrobials. The defining structural component is a furan ring with a nitro group attached. In the present investigation, electron attachment to 2-nitrofuran (C₄H₃NO₃), which is considered as a potential radiosensitizer candidate for application in radiotherapy, has been studied in a crossed electron-molecular beams experiment. The present results indicate that low-energy electrons with kinetic energies of about 0-12 eV effectively decompose the molecule. In total, twelve fragment anions were detected within the detection limit of the apparatus, as well as the parent anion of 2-nitrofuran. One major resonance region of ≈0-5 eV is observed in which the most abundant anions NO₂^-, C₄H₃O^-, and C₄H₃NO₃^- are detected. The experimental results are supported by ab initio calculations of electronic states in the resulting anion, thermochemical thresholds, connectivity between electronic states of the anion, and reactivity analysis in the hot ground state.

Keywords: electron attachment; fragmentation; low-energy electron; nitrofuran; radiosensitizer; reduction.

Figure 1

Negative ion mass spectrum of 2-nitrofuran upon electron attachment. The spectrum was obtained by summing 11 individual spectra recorded at electron energies from 0 to 10 eV, in steps of 1 eV. The inset shows anionic fragments formed in the range of m/z 25–28 with improved mass resolution. A schematic representation of the molecule is also shown.

Figure 2

Anion efficiency curves of the four most abundant anions observed in the present electron attachment study with 2-nitrofuran (2-NIF), (a) the parent anion C₄H₃NO₃⁻, (b) NO₂⁻, (c) C₄H₃O⁻ and (d) C₃H₃O⁻, respectively.

Figure 3

Anion efficiency curves for the anionic fragments with masses between 16 and 42 u formed upon dissociative electron attachment (DEA) to 2-NIF.

Figure 4

Total ion yield of measured anions formed upon electron attachment to 2-NIF (upper panel) and calculated position of resonances along with target orbitals for each calculated state (lower panel). The total ion yield was obtained by the sum of the mass-selected anion yields shown in Figure 2 and Figure 3. The excited states were calculated at the TD-CAM-B3LYP/aug-cc-pVTZ//B3LYP/aug-cc-pVTZ level of theory. Twenty-five excited states were considered, with transition probability put equal for every transition. Apart from the dipole bound state, only non-diffuse states and states that can be created by direct electron attachment to the neutral molecule were considered; therefore, higher electronic states are not described as D_x, and only the D₀ state is explicitly denoted. Calculated transition energies for the target anionic states are shifted by –0.60 eV (negatively taken vertical electron affinity calculated at the CCSD/aug-cc-pVTZ//B3LYP/aug-cc-pVDZ level) and –0.18 eV (average difference of excitation energies between TD-CAM-B3LYP and EOM-CCSD with the aug-cc-pVDZ basis set for first 25 excited states), i.e., all states are shifted by –0.78 eV. For a description of the dipole-bound state, additional basis set functions were employed (see Section 2).

Figure 5

Reaction pathways in the electronically excited nitrofuran anion optimized at the CASSCF(3,6)/6–31g* level and single-point recalculated at the MRCI(3,6)/6–31g* level (black lines and red crosses, respectively). The Franck–Condon (FC) point (first point), the minimum on the excited state potential energy surface (second point), constrained optimization in the D₁ state with respect to the NO₂ group rotation (points 3–11) and interpolation to a conical intersection with pyramidalized NO₂ group (points 12–16) are shown. Orbitals corresponding to excitations in the FC point were calculated at the CASSCF level. Note that due to the small basis set used, not all states depicted in Figure 4 could be reproduced here (see Section 2 for details).

Figure 6

Potential energy surface mapping dissociation channels in 2-NIF⁻. Calculated at the CCSD/aug-cc-pVTZ//B3LYP/aug-cc-pVTZ level, the respective B3LYP values are provided in parentheses. The energy is given in eV.