With the aim of enhancing the biological activity of ruthenium-nitrosyl complexes, new compounds with four equatorially bound indazole ligands, namely, trans-[RuCl(Hind)(NO)]Cl·HO ([3]Cl·HO) and trans-[RuOH(Hind)(NO)]Cl·HO ([4]Cl·HO), have been prepared from trans-[Ru(NO)(Hind)] ([2]). When the pH-dependent solution behavior of [3]Cl·HO and [4]Cl·HO was studied, two new complexes with two deprotonated indazole ligands were isolated, namely [RuCl(ind)(Hind)(NO)] ([5]) and [RuOH(ind)(Hind)(NO)] ([6]). All prepared compounds were comprehensively characterized by spectroscopic (IR, UV-vis, H NMR) techniques. Compound [2], as well as [3]Cl·2(CH)CO, [4]Cl·2(CH)CO, and [5]·0.8CHCl, the latter three obtained by recrystallization of the first isolated compounds (hydrates or anhydrous species) from acetone and dichloromethane, respectively, were studied by X-ray diffraction methods. The photoinduced release of NO in [3]Cl and [4]Cl was investigated by cyclic voltammetry and resulting paramagnetic NO species were detected by EPR spectroscopy. The quantum yields of NO release were calculated and found to be low (3-6%), which could be explained by NO dissociation and recombination dynamics, assessed by femtosecond pump-probe spectroscopy. The geometry and electronic parameters of Ru species formed upon NO release were identified by DFT calculations. The complexes [3]Cl and [4]Cl showed considerable antiproliferative activity in human cancer cell lines with IC values in low micromolar or submicromolar concentration range and are suitable for further development as potential anticancer drugs. p53-dependence of Ru-NO complexes [3]Cl and [4]Cl was studied and p53-independent mode of action was confirmed. The effects of NO release on the cytotoxicity of the complexes with or without light irradiation were investigated using NO scavenger carboxy-PTIO.

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Abstract"Kramers pairs symmetry breaking" is evaluated at the 2-component (2c) Kramers unrestricted and/or general complex Hartree-Fock (GCHF) level of theory, and its analogy with "spin contamination" at the 1-component (1c) unrestricted Hartree-Fock (UHF) level of theory is emphasized. The GCHF "Kramers pairs symmetry breaking" evaluation is using the square of overlaps between the set of occupied spinorbitals with the projected set of Kramers pairs. In the same fashion, overlaps between α and β orbitals are used in the evaluation of "spin contamination" at the UHF level of theory. In this manner, UHFŜ 2 expectation value is made formally extended to the GCHF case. The directly evaluated GCHF expectation value of theŜ 2 operator is considered for completeness. It is found that the 2c GCHF Kramers pairs symmetry breaking has a very similar extent in comparison to the 1c UHF spin contamination. Thus higher excited states contributions to the 1c so 2c unrestricted wave functions of open shell systems have almost the same extent and physical consequences. Moreover, it is formally shown that a single determinant wave function in the restricted open shell Kramers case has the expectation value ofK 2 operator equal to the negative number of open shell electrons, while the eigenvalue ofK 2 for the series of simple systems (H, He, He*-triplet, Li and Li*-quartet) are found to be equal to minus the square of the number of open shell electrons. The concept of unpaired electron density is extended to the GCHF regime and compared to UHF and restricted open shell Hartree-Fock spin density. The "collinear" and "noncollinear" analogs of spin density at the GCHF level of theory are considered as well. Spin contamination and/or Kramers pairs symmetry breaking, spin