Hydrogen(electron-deuteron) studies of the deuteron at high squared momentum transfer

A high resolution study of the quasielastic 2 H(e, e'p)n reaction was performed in Hall A at the Thomas Jefferson Accelerator Facility in Newport News, Virginia. The measurements were performed at a central momentum transfer of : q: ∼ 2400 MeV/c, and at a central energy transfer of ω ∼ 1500 MeV, a four momentum transfer Q2 = 3.5 (GeV/c)2, covering missing momenta from 0 to 0.5 GeV/c. The majority of the measurements were performed at Φ = 180° and a small set of measurements were done at Φ = 0°. The Hall A High Resolution Spectrometers (HRS) were used to detect coincident electrons and protons, respectively. Absolute 2H(e, e'p) n cross sections were obtained as a function of the recoiling neutron scattering angle with respect to [special characters omitted]. The experimental results were compared to a Plane Wave Impulse Approximation (PWIA) model and to a calculation that includes Final State Interaction (FSI) effects. Experimental 2H(e, e'p)n cross sections were determined with an estimated systematic uncertainty of 7%. The general features of the measured cross sections are reproduced by Glauber based calculations that take the motion of the bound nucleons into account (GEA). Final State Interactions (FSI) contributions were found to depend strongly on the angle of the recoiling neutron with respect to the momentum transfer and on the missing momentum. We found a systematic deviation of the theoretical prediction of about 30%. At small &thetas; nq (&thetas;nq < 60°) the theory overpredicts the cross section while at large &thetas; nq (&thetas;nq > 80°) the theory underestimates the cross sections. We observed an enhancement of the cross section, due to FSI, of about 240%, as compared to PWIA, for a missing momentum of 0.4 GeV/c at an angle of 75°. For missing momentum of 0.5 GeV/c the enhancement of the cross section due to the same FSI effects, was about 270%. This is in agreement with GEA. Standard Glauber calculations predict this large contribution to occur at an angle of 90°. Our results show that GEA better describes the 2H(e, e'p)n reaction.

Biomimetic modeling of the nitrogen-centered radical postulated to occur during the inhibition of ribonucleotide reductases by 2'-azido-2'-deoxynucleotides

Ribonucleotide reductases (RNR) are essential enzymes that catalyze the reduction of ribonucleotides to 2'-deoxyribonucleotides, which is a critical step that produces precursors for DNA replication and repair. The inactivation of RNR, logically, would discontinue producing the precursors of the DNA of viral or cancer cells, which then would consequently end the cycle of DNA replication. Among different compounds that were found to be inhibitors of RNR, 2'-azido-2'-deoxynucleotide diphosphates (N3NDPs) have been investigated in depth as potent inhibitors of RNR. Decades of investigation has suggested that the inactivation of RNR by N3NDPs is a result of the formation of a nitrogen-centered radical (N·) that is covalently attached to the nucleotide at C3' and cysteine molecule C225 [3'-C(R-S-N·-C-OH)]. Biomimetic simulation reactions for the generation of the nitrogen-centered radicals similar to the one observed during the inactivation of the RNR by azionuclotides was investigated. The study included several modes: (i) theoretical calculation that showed the feasibility of the ring closure reaction between thiyl radicals and azido group; (ii) synthesis of the model azido nucleosides with a linker attached to C3' or C5' having a thiol or vicinal dithiol functionality; (iii) generation of the thiyl radical under both physiological and radiolysis conditions whose role is important in the initiation on RNR cascades; and (iv) analysis of the nitrogen-centered radical species formed during interaction between the thiyl radical and azido group by electron paramagnetic resonance spectroscopy (EPR). Characterization of the aminyl radical species formed during one electron attachment to the azido group of 2'-azido-2'-deoxyuridine and its stereospecifically labelled 1'-, 2'-, 3'-, 4'- or 5,6-[2H 2]-analogues was also examined. This dissertation gave insight toward understanding the mechanism of the formation of the nitrogen-centered radical during the inactivation of RNRs by azidonucleotides as well as the mechanism of action of RNRs that might provide key information necessary for the development of the next generation of antiviral and anticancer drugs.