Cancer affects a major part of the worldwide population, and, to minimize deaths, the diagnosis in the early stages of the disease is fundamental. Thus, to improve diagnosis and treatment new potential spectroscopic probes are crucial. Benzothiazole derivates present antitumor properties and are highly selective and interact strongly with the enzyme phosphoinositide 3-kinase (PI3K), which was associated with cell proliferation and breast cancer cells. In this paper, the rhenium shielding tensors (187Re(σ)) and hydrogen and carbon chemical shifts (1H(δ) and 13C(δ)) of the Re(CO)3(NNO) complex conjugated with 2-(4'-aminophenyl)benzothiazole (ReABT) were evaluated. A statistical HCA model was used to analyze the best DFT protocol to compute σ and δ values and to evaluate the relativistic effects, both in the basis set and Hamiltonian as well as the functionals M06L or PBE0. The best protocol was applied to obtain 187Re(σ) of the ReABT complex in different environments (gas phase, solution, and in the active site of the PI3K enzyme). The results point out that 187Re(σ) values of the ReABT complex change significantly when the complex is docked in the PI3K enzyme.

Center for Basic and Applied Research Faculty of Informatics and Management University of Hradec Kralove Hradec Kralove Czech Republic

Chemistry Department Federal University of Lavras P O Box 3037 Lavras MG 37200 900 Brazil

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Sung H et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J Clin 71(3):209–249. https://doi.org/10.3322/caac.21660 DOI

Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA A Cancer J Clin 69(1):7–34. https://doi.org/10.3322/caac.21551 DOI

Jafari SH et al (2018) Breast cancer diagnosis: imaging techniques and biochemical markers. J Cell Physiol 233(7):5200–5213. https://doi.org/10.1002/jcp.26379 PubMed DOI

He Z et al (2020) A review on methods for diagnosis of breast cancer cells and tissues. Cell Prolif 53(7):e12822. https://doi.org/10.1111/cpr.12822 PubMed DOI PMC

Wang L (2017) Early diagnosis of breast cancer. Sensors. 17(7). https://doi.org/10.3390/s17071572

Waks AG, Winer EP (2019) Breast cancer treatment: a review. JAMA 321(3):288–300. https://doi.org/10.1001/jama.2018.19323 PubMed DOI

Galvão E et al (2011) Breast cancer proteomics: a review for clinicians. J Cancer Res Clin Oncol 137(6):915–925. https://doi.org/10.1007/s00432-011-0978-0 PubMed DOI

Barba D et al (2021) Breast cancer, screening and diagnostic tools: all you need to know. Crit Rev Oncol Hematol 157:103174. https://doi.org/10.1016/j.critrevonc.2020.103174 PubMed DOI

DeSantis CE et al (2019) Breast cancer statistics, 2019. CA A Cancer J Clin 69(6):438–451. https://doi.org/10.3322/caac.21583 DOI

Pereira BTL et al (2017) Exploring EPR parameters of ⁹⁹Tc complexes for designing new MRI probes: coordination environment, solvent, and thermal effects on the spectroscopic properties. J Chem 2017:8102812. https://doi.org/10.1155/2017/8102812 DOI

Corrêa S et al (2021) Hybrid materials based on magnetic iron oxides with benzothiazole derivatives: a plausible potential spectroscopy probe. Int J Mol Sci 22(8). https://doi.org/10.3390/ijms22083980

Gonçalves MA et al (2015) Probing thermal and solvent effects on hyperfine interactions and spin relaxation rate of δ-FeOOH(100) and [MnH3buea(OH)]2−: toward new MRI probes. Comput Theor Chem 1069:96–104. https://doi.org/10.1016/j.comptc.2015.07.006 DOI

Pereira BTL et al (2019) First attempts of the use of 195Pt NMR of phenylbenzothiazole complexes as spectroscopic technique for the cancer diagnosis. Molecules 24(21):3970. https://doi.org/10.3390/molecules24213970 DOI PMC

Tzanopoulou S et al (2006) Synthesis, characterization, and biological evaluation of M (I)(CO) 3 (NNO) complexes (M= Re, 99mTc) conjugated to 2-(4-aminophenyl) benzothiazole as potential breast cancer radiopharmaceuticals. J Med Chem 49(18):5408–5410. https://doi.org/10.1021/jm0606387 PubMed DOI

Mancini DT et al (2014) 99Tc NMR as a promising technique for structural investigation of biomolecules: theoretical studies on the solvent and thermal effects of phenylbenzothiazole complex. Magn Reson Chem 52(4):129–137. https://doi.org/10.1002/mrc.4043 PubMed DOI

Tzanopoulou S et al (2010) Evaluation of Re and 99mTc complexes of 2-(4′-aminophenyl) benzothiazole as potential breast cancer radiopharmaceuticals. J Med Chem 53(12):4633–4641. https://doi.org/10.1021/jm1001293 PubMed DOI

Machura B et al (2011) Novel Re(I) tricarbonyl complexes of chelating ligands with aromatic N-heterocycle ring and aliphatic amine donor – synthesis, spectroscopic characterization, X-ray structure and DFT calculations. Polyhedron 30(13):2275–2285. https://doi.org/10.1016/j.poly.2011.06.001 DOI

Machura B et al (2013) Tricarbonyl rhenium(I) complex of benzothiazole – synthesis, spectroscopic characterization, X-ray crystal structure and DFT calculations. J Organomet Chem 724:82–87. https://doi.org/10.1016/j.jorganchem.2012.10.020 DOI

Breitz HB et al (1995) Pharmacokinetics and normal organ dosimetry following intraperitoneal rhenium-186-labeled monoclonal antibody. J Nucl Med 36(5):754–761 PubMed

Mavroidi B et al (2016) Palladium (II) and platinum (II) complexes of derivatives of 2-(4′-aminophenyl) benzothiazole as potential anticancer agents. Inorg Chim Acta 444:63–75. https://doi.org/10.1016/j.ica.2016.01.012 DOI

Long N, Wong W-T (2014) The chemistry of molecular imaging. John Wiley & Sons.

Gonçalves MA et al (2014) Dynamics, NMR parameters and hyperfine coupling constants of the Fe3O4(100)–water interface: implications for MRI probes. Chem Phys Lett 609:88–92. https://doi.org/10.1016/j.cplett.2014.06.030 DOI

Ramalho TC, Taft CA (2005) Thermal and solvent effects on the NMR and UV parameters of some bioreductive drugs. J Chem Phys 123(5):054319. https://doi.org/10.1063/1.1996577 PubMed DOI

Srivastava D, Atluri SN (2002) Computational nanotechnology: a current perspective. Comput Model Eng Sci 3(5):531–538

Hassanzadeganroudsari M et al (2021) Computational chemistry to repurposing drugs for the control of COVID-19. Biologics 1(2):111–128. https://doi.org/10.3390/biologics1020007 DOI

Ramalho TCM, Bühl M (2005) Probing NMR parameters, structure and dynamics of 5-nitroimidazole derivatives. Density functional study of prototypical radiosensitizers. Magn Reson Chem 43(2):139–146. https://doi.org/10.1002/mrc.1514 PubMed DOI

Bühl M et al (1999) The DFT route to NMR chemical shifts. J Comput Chem 20(1):91–105. https://doi.org/10.1002/(SICI)1096-987X(19990115)20:1%3c91::AID-JCC10%3e3.0.CO;2-C DOI

Bühl M (2002) Density functional computation of 55Mn NMR parameters. Theoret Chem Acc 107(6):336–342. https://doi.org/10.1007/s00214-002-0338-x DOI

Helgaker T, Jaszunski M, Ruud K (1999) Ab initio methods for the calculation of NMR shielding and indirect spin-spin coupling constants. Chem Rev 99:293–352 DOI

Pyykkö P (2012) Relativistic effects in chemistry: more common than you thought. Annu Rev Phys Chem 63:45–64. https://doi.org/10.1146/annurev-physchem-032511-143755 PubMed DOI

Lin Y-S et al (2013) Long-range corrected hybrid density functionals with improved dispersion corrections. J Chem Theory Comput 9(1):263–272. https://doi.org/10.1021/ct300715s PubMed DOI

Pantazis DA et al (2008) All-electron scalar relativistic basis sets for third-row transition metal atoms. J Chem Theory Comput 4(6):908–919. https://doi.org/10.1021/ct800047t PubMed DOI

van Wüllen C (1998) Molecular density functional calculations in the regular relativistic approximation: method, application to coinage metal diatomics, hydrides, fluorides and chlorides, and comparison with first-order relativistic calculations. J Chem Phys 109(2):392–399. https://doi.org/10.1063/1.476576 DOI

Ferreira SC et al (2007) Box-Behnken design: an alternative for the optimization of analytical methods. Anal Chim Acta 597(2):179–186. https://doi.org/10.1016/j.aca.2007.07.011 PubMed DOI

da Rocha EP et al (2016) Insights into the value of statistical models and relativistic effects for the investigation of halogenated derivatives of fluorescent probes. Theoret Chem Acc 135(5):135. https://doi.org/10.1007/s00214-016-1862-4 DOI

Nunes CA et al (2012) Chemoface: a novel free user-friendly interface for chemometrics. J Braz Chem Soc 23:2003–2010. https://doi.org/10.1590/S0103-50532012005000073 DOI

Ditchfield R (1974) Self-consistent perturbation theory of diamagnetism. Mol Phys 27(4):789–807. https://doi.org/10.1080/00268977400100711 DOI

Wolinski K, Hinton JF, Pulay P (1990) Efficient implementation of the gauge-independent atomic orbital method for NMR chemical shift calculations. J Am Chem Soc 112(23):8251–8260 DOI

Zhao Y, Truhlar DG (2006) A new local density functional for main-group thermochemistry, transition metal bonding, thermochemical kinetics, and noncovalent interactions. J Chem Phys 125(19):194101. https://doi.org/10.1063/1.2370993 PubMed DOI

Adamo C, Barone V (1999) Toward reliable density functional methods without adjustable parameters: The PBE0 model. J Chem Phys 110(13):6158–6170. https://doi.org/10.1063/1.478522 DOI

Autschbach J (2004) The calculation of NMR parameters in transition metal complexes. Principles and Applications of Density Functional Theory in Inorganic Chemistry I. p. 1-48. https://doi.org/10.1007/b97936

Zhao Y, Truhlar DG (2008) Improved description of nuclear magnetic resonance chemical shielding constants using the M06-L meta-generalized-gradient-approximation density functional. J Phys Chem A 112(30):6794–6799. https://doi.org/10.1021/jp804583d PubMed DOI

Jiménez-Pulido SB et al (2016) A combined experimental and DFT investigation on the structure and CO-releasing properties of mono and binuclear fac-Re I (CO) 3 complexes with 5-pyridin-2-ylmethylene-amino uracils. Dalton Trans 45(38):15142–15154. https://doi.org/10.1039/C6DT02208A PubMed DOI

Vícha J et al (2015) Structure, solvent, and relativistic effects on the NMR chemical shifts in square-planar transition-metal complexes: assessment of DFT approaches. Phys Chem Chem Phys 17(38):24944–24955. https://doi.org/10.1039/C5CP04214C PubMed DOI

Neese F (2012) The ORCA program system. Wiley Interdisc Rev Comput Mol Sci 2(1):73–78. https://doi.org/10.1002/WCMS.81 DOI

Thomsen R, Christensen MH (2006) MolDock: a new technique for high-accuracy molecular docking. J Med Chem 49(11):3315–3321. https://doi.org/10.1021/jm051197e PubMed DOI

D’Angelo ND et al (2011) Discovery and optimization of a series of benzothiazole phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitors. J Med Chem 54(6):1789–1811. https://doi.org/10.1021/jm1014605 PubMed DOI

da Cunha EFF et al (2009) 3D-QSAR CoMFA/CoMSIA models based on theoretical active conformers of HOE/BAY-793 analogs derived from HIV-1 protease inhibitor complexes. Eur J Med Chem 44(11):4344–4352. https://doi.org/10.1016/j.ejmech.2009.05.016 PubMed DOI

Pinheiro JR et al (2008) Novel anti-HIV cyclotriazadisulfonamide derivatives as modeled by ligand-and receptor-based approaches. Bioorg Med Chem 16(4):1683–1690. https://doi.org/10.1016/j.bmc.2007.11.020 PubMed DOI

Widdifield CM, Perras FA, Bryce DL (2015) Solid-state 185/187 Re NMR and GIPAW DFT study of perrhenates and Re 2 (CO) 10: chemical shift anisotropy, NMR crystallography, and a metal–metal bond. Phys Chem Chem Phys 17(15):10118–10134. https://doi.org/10.1021/jm1014605 PubMed DOI

Ramalho TC, Santos LA, da Cunha EFF (2013) Thermodynamic framework of hydrophobic/electrostatic interactions. J Biomol Struct Dyn 31(9):995–1000. https://doi.org/10.1080/07391102.2012.748539 PubMed DOI

Molecular Dynamics-Assisted Interaction Between HABT and PI3K Enzyme: Exploring Metastable States for Promising Cancer Diagnosis Applications