Cd Hyperfine Interactions in DNA Bases and DNA of Mouse Strains Infected with Trypanosoma cruzi Investigated by Perturbed Angular Correlation Spectroscopy and ab Initio Calculations Philippe A. D. Petersen, † Andreia S. Silva, ‡ Marcos B. Gonc ̧ alves, † Andre ́ L. Lapolli, ‡ Ana Maria C. Ferreira, § Artur W. Carbonari, ‡ and Helena M. Petrilli* ,† † Departamento de Física de Materiais e Mecâ nica, Instituto de Física, Universidade de Sã o Paulo, CEP 05508-090 Sã o Paulo, SP, Brazil ‡ Laborató rio de Interaç õ es Hiperfinas, Instituto de Pesquisas Energe ́ ticas e Nucleares, IPEN-CNEN/SP, 05508-000 Sã o Paulo, SP, Brazil § Departamento de Química Fundamental, Instituto de Química, Universidade de Sã o Paulo, CEP 05508-000 Sã o Paulo, SP, Brazil ABSTRACT: In this work, perturbed angular correlation (PAC) spectroscopy is used to study differences in the nuclear quadrupole interactions of Cd probes in DNA molecules of mice infected with the Y-strain of Trypanosoma cruzi. The possibility of investigating the local genetic alterations in DNA, which occur along generations of mice infected with T. cruzi, using hyperfine interactions obtained from PAC measurements and density functional theory (DFT) calculations in DNA bases is discussed. A comparison of DFT calculations with PAC measurements could determine the type of Cd coordination in the studied molecules. To the best of our knowledge, this is the first attempt to use DFT calculations and PAC measurements to investigate the local environment of Cd ions bound to DNA bases in mice infected with Chagas disease. The obtained results also allowed the detection of local changes occurring in the DNA molecules of different generations of mice infected with T. cruzi, opening the possibility of using this technique as a complementary tool in the characterization of complicated biological systems. T he detection of hyperfine quantities is the goal of many spectroscopic experimental methods, such as Mö ssbauer spectroscopy, electron paramagnetic resonance (EPR), per- turbed angular correlation (PAC), and nuclear magnetic resonance (NMR). 1,2 PAC spectroscopy has some advantages over other hyperfine interactions techniques, being better suited to the study of biomolecules, mainly because it requires an extremely small amount of sample, which allows experiments to be performed under physiological conditions. Further, it can be applied to different physical states, such as samples in vivo, samples in solution, frozen samples, etc. Moreover, PAC spectroscopy can also explore the dynamics of biomolecules. 3 PAC spectroscopy provides information about the local electronic structure at the probe nucleus site via the electric hyperfine interaction between the nuclear charge distribution and the electronic surrounding charge distribution, the so-called nuclear quadrupole interaction (NQI). More specifically, in terms of the electric contribution, the electric quadrupole moment Q of the nucleus interacts with the electric field gradient (EFG) at the nuclear site produced by charges outside the nucleus. The EFG is very sensitive to the electric fields arising from charges within the first coordination shell around the probe nuclei. 1 Therefore, via the EFG, PAC spectroscopy can probe an extremely high spatial resolution, within a single atomic bond length. On the other hand, because the EFG is a ground state property, it is also easily calculated as long as the charge density around the probe nucleus is known from first- principles calculations, which can, today, be reliably performed in the framework of the density functional theory (DFT). Because of its high sensitivity, the EFG is a very powerful parameter that can be used in comparisons between experimental and calculated values to investigate local environ- ments. In bioinorganic chemistry, the PAC technique is used to measure the hyperfine interactions at a specific metal probe (e.g., Cd, In, Ta, or Hf) bound to key biomolecules, such as deoxyribonucleic acid (DNA) or proteins, providing structural and dynamic information about the contact site with the probe. 4 In this work, PAC spectroscopy was used to investigate the hyperfine interactions at Cd probe nuclei bound to free nucleobase (NB) molecules as well as to DNA of different mouse strains infected with Trypanosoma cruzi, the protozoan that causes Chagas disease. Differences in the resistance of people to T. cruzi indicate that the genetic constitution of the host can significantly influence the development of the disease. 5,6 Further, the analysis of mouse strains infected with T. cruzi suggests the importance of the genetic constitution on the survival of the host. 5−7 On the other hand, DFT Received: December 18, 2013 Revised: April 30, 2014 Published: May 6, 2014 Article pubs.acs.org/biochemistry © 2014 American Chemical Society 3446 dx.doi.org/10.1021/bi401680h | Biochemistry 2014, 53, 3446−3456