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Novel ruthenium(III) complexes of general formula Na[RuCl2(L1-3-N,O)2] where L(1-3)denote deprotonated Schiff bases (HL1-HL3) derived from 5-substituted salicyladehyde and alkylamine (propyl- or butylamine) were prepared and characterized based on elemental analysis, mass spectra, infrared, electron spin/paramagnetic resonance (ESR/EPR) spectroscopy, and cyclovoltammetric study. Optimization of five isomers of complex C1 was done by DFT calculation. The interaction of C1-C3 complexes with DNA (Deoxyribonucleic acid) and BSA (Bovine serum albumin) was investigated by electron spectroscopy and fluorescence quenching. The cytotoxic activity of C1-C3 was investigated in a panel of four human cancer cell lines (K562, A549, EA.hy926, MDA-MB-231) and one human non-tumor cell line (MRC-5). Complexes displayed an apparent cytoselective profile, with IC50values in the low micromolar range from 1.6 ± 0.3 to 23.0 ± 0.1 µM. Cisplatin-resistant triple-negative breast cancer cells MDA-MB-231 displayed the highest sensitivity to complexes, with Ru(III) compound containing two chlorides and two deprotonated N-propyl-5-chloro-salicylidenimine (hereinafter C1) as the most potent (IC50= 1.6 µM), and approximately ten times more active than cisplatin (IC50= 21.9 µM). MDA-MB-231 cells treated for 24 h with C1 presented with apoptotic morphology, as seen by acridine orange/ethidium bromide staining, while 48 h of treatment induced DNA fragmentation, and necrotic changes in cells, as seen by flow cytometry analysis. Drug-accumulation study by inductively coupled plasma mass spectrometry (ICP-MS) demonstrated markedly higher intracellular accumulation of C1 compared with cisplatin.

Three new coordination compounds of copper(II) with glycine (HGly) and 2,2'-bipyridine (bipy) were synthesized by solution-based and mechanochemical methods: [Cu(Gly)(H2O)(bipy)][Cu(Gly)(SO4)(bipy)]·6H2O (1a·6H2O), [Cu(Gly)(H2O)(bipy)]2SO4 (1b), [Cu(Gly)(H2O) (bipy)]2SO4·H2O (1b·H2O). The amount of water in the reaction mixture influenced the product of crystallization. All compounds were characterized by X-ray diffraction methods and form 1D infinite chains or 2D sheets of complex ions connected by π-interactions. Compounds 1a·6H2O and 1b were characterized by X-band electron spin resonance (ESR) spectroscopy and the values of g-tensors for Cu(II) ions were determined. Compounds 1a·6H2O and 1b showed pronounced antiproliferative activity toward a panel of six human cell lines. The most impared was HepG2 cell line at 10−5 mol dm−3 concentration (74.5 % reduction of cell growth) followed by moderate activity toward KATO III, Caco-2, MDA-MB-231, PANC-1 and MRC-5 cells at 10−4 mol dm−3 concentration of compounds 1a·6H2O and 1b. Generally, both compounds express similar antiproliferative effect on evaluated cells.

Staklasto stanje tvari je amorfno stanje materijala koje najčešće nastaje brzim hlađenjem kapljevine ispod temperature staklišta 𝑇𝑔. Takav neuređeni sustav nije u stanju termodinamičke ravnoteže i s obzirom na minimum energije svi stupnjevi slobode nisu optimizirani. Izostanak dugodosežne translacijske i rotacijske simetrije dovodi do pojave mnogih interesantnih fizičkih fenomena poput bozonskog vrška. Ako su takovi sustavi paramagnetski ili ih dopiramo paramagnetskim centrima, moguće ih je proučavati metodom elektronske spinske rezonancije (ESR) pri čemu utjecaj dinamike spinova jezgara promatranog materijala na spin elektrona možemo detektirati kao gubitak fazne koherencije elektronskih spinova. Koristeći specifične impulsne sljedove u ESR eksperimentima proučavali smo razlike spinske dinamike između staklastih i kristalastih realizacija istog materijala. Cilj našeg rada je doprinijeti razumijevanju utjecaja neuređenosti na dinamičke efekte opažene u staklima na niskim temperaturama u odnosu na kristalasto stanje, a za koje još ne postoji usuglašeni teorijski opis. Koristeći različite impulsne tehnike, a posebice inačicu konstantnog vremena Carr-Purcell-Meiboom-Gill (CPMG) impulsnih sljedova proučavali smo dva modelna sustava: etanol dopiran paramagnetskim nitroksilnim radikalom TEMPO i trehalozu podvrgnutu 𝛾-zračenju. Oba materijala proučavali smo u staklastom i polikristalastom stanju na temperatu-rama 𝑇≤20 K što odgovara temperaturama 𝑇≤0.2 𝑇𝑔. U tom temperaturnom intervalu molekulska dinamika odgovorna za relaksaciju spinskog sustava u termodinamičku ravnotežu je libracija molekulskih segmenata i kvantno-mehaničko tuneliranje. Dinamičkim rasprezanjem hiperfinog međudjelovanja spina elektrona sa spinovima protona matrice proučavali smo utjecaj neuređenosti molekulskog pakiranja na spinsku dinamiku. U slučaju etanola nuklearna spektralna difuzija (NSD) pokazala se dominantnim mehanizmom gubitka fazne koherencije spinova elektrona. Međutim, u slučaju trehaloze uz NSD uočili smo i dodatni relaksacijski mehanizam, trenutnu difuziju, koji onemogućuje direktan zaključak o utjecaju neuređenosti na spinsku dinamiku jer interferira s utjecajem NSD u gubitku fazne koherencije elektronskih spinova. Dobiveni eksperimentalni podaci predstavljaju osnovu za daljnja teorijska razmatranja modela molekulske dinamike u neuređenom materijalu jer poznavanje dinamičkih svojstava nuklearnih spinova (NSD), koja detektiramo putem hiperfinog međudjelovanja, direktno odražavaju dinamička svojstva promatranog materijala. The glassy state of matter is the amorphous state of the material most commonly formed by rapid cooling of the liquid below the glass transition temperature 𝑇𝑔. Such disordered system is not in a state of thermodynamic equilibrium, and with respect to the minimum energy, all degrees of freedom are not optimized. The absence of long-range translational and rotational symmetry leads to the appearance of many interesting physical phenomena such as the boson peak. If these systems are paramagnetic or if they are doped with paramagnetic centres, it is possible to study them using the electron spin resonance (ESR) method in which the influence of the spin dynamics of the nuclei of the observed material on the electron spin can be detected as a phase decoherence of electron spins. Using specific pulse sequences in ESR experiments, we have studied the differences between spin dynamics of glassy and crystalline realization of the same material. The aim of our work is to contribute to the understanding of the influence of the disorder on the dynamic effects observed in glass at low temperatures but not in the crystalline state, for which a theoretical description has not been agreed upon yet. Using various pulse techniques and focusing on a constant-time version of the Carr-Purcell-Meiboom-Gill (CPMG) pulse sequences, we have studied two model systems: ethanol doped with nitroxyl radical TEMPO and 𝛾-irradiated trehalose. Both materials were studied in glassy and polycrystalline state at temperatures 𝑇≤20 K which correspond to temperatures 𝑇≤0.2 𝑇𝑔. In this temperature interval, molecular dynamics responsible for the relaxation of the spin system into thermodynamic equilibrium is the libration of molecular segments and quantum-mechanical tunnelling. Using dynamic decoupling of hyperfine interaction of electron spin with matrix proton spins, we studied the influence of disorder of molecular packing on spin dynamics. In the case of ethanol, nuclear spectral diffusion (NSD) proved to be a dominant mechanism of the phase decoherence of electron spins. However, in the case of trehalose, along with NSD, we have detected additional relaxation mechanisms, instantaneous diffusion, which prevents a direct conclusion about the influence of disorder on spin dynamics because it interferes with NSD in the phase decoherence of electron spins. The obtained experimental data are the basis for further theoretical studies of the molecular dynamics models in a disordered material since dynamic properties of nuclear spins (NSD), which are detected through the hyperfine interaction, directly reflect dynamic properties of the observed material.

Staklasto stanje tvari je amorfno stanje materijala koje nastane brzim hlađenjem tekućine. Takav neuređeni sustav nije u stanju termodinamičke ravnoteže i s obzirom na minimum energije svi stupnjevi slobodne nisu optimizirani. Izostanak dugodosežne translacijske i rotacijske simetrije dovodi do pojave mnogih interesantnih fizičkih fenomena poput bozonskog vrška. Ako su takovi sustavi paramagnetski ili ih dopiramo paramagnetskim centrima, moguće ih je proučavati metodom elektronske spinske rezonancije (ESR). Koristeći specifične impulsne slijedove u ESR eksperimentima proučavali smo razlike između staklastih i kristalnih realizacija istog materijala s ciljem pronalaženja prikladnog eksperimentalnog parametra za opis neuređenosti staklastih sustava. Cilj našeg rada je doprinijeti razumijevanju utjecaja neuređenosti na dinamičke efekte opažene u staklima na niskim temperaturama u odnosu na kristalinično stanje, a za koja još ne postoji usuglašeni teorijski opis. Koristeći inačicu konstantnog vremena Carr- Purcell-Meiboom-Gill (CPMG) impulsnih slijedova proučavali smo dva modelna sustava: etanol dopiran paramagnetskim nitroksilnim radikalom TEMPO i trehalozu podvrgnutu γ-zračenju. Oba materijala proučavali smo u staklastom i polikristaliničnom stanju. Proučili smo hiperfinu interakciju spina elektrona sa spinovima protona matrice kao funkciju neuređenosti, tj. molekulskog pakiranja. U slučaju etanola nuklearna spektralna difuzija (NSD) pokazala se dominantnim mehanizmom gubitka fazne koherencije spinova elektrona [1], dok u slučaju trehaloze uz NSD uočavamo i dodatne relaksacijske mehanizme za koje pretpostavljamo da potječu od elektron-elektron spinske dipolarne interakcije između različitih radikala u uzorku. Dobiveni eksperimentalni podaci predstavljaju osnovu za daljnja teorijska razmatranja modela molekulske dinamike u neuređenom materijalu jer poznavanje dinamičkih svojstava nuklearnih spinova (NSD) koja detektiramo putem hiperfine interakcije direktno odražavaju dinamička svojstva promatranog materijala.

Using specific pulse sequences in ESR experiments, we have studied the differences between glassy and crystalline realization of the same material with the aim of finding a suitable experimental parameter for describing the disorder in glassy systems. The aim of our work is to contribute to the understanding of the influence of the disorder on the dynamic effects observed in glass at low temperatures for which a theoretical description has not been agreed upon yet. Focusing on a constant- time version of the Carr-Purcell-Meiboom-Gill (CPMG) pulse sequences, we studied two model systems: ethanol doped with nitroxyl radical TEMPO and γ- irradiated trehalose. Both materials were studied in glassy and polycrystalline state. We studied the hyperfine interaction of the electron spin with the spins of the matrix protons as a function of disorder ; i.e. molecular packing. In the case of ethanol, nuclear spectral diffusion (NSD) proved to be a dominant mechanism of the phase decoherence of electron spins [1], while in the case of trehalose, along with NSD, we have detected additional relaxation mechanisms that are supposed to derive from the electron- electron spin dipolar interaction between different radicals in the sample. The obtained experimental data are the basis for further theoretical studies of the molecular dynamics models in a disordered material since dynamic properties of nuclear spins (NSD), which are detected through the hyperfine interaction, directly reflect properties of the observed material. This work is supported by Croatian Science Foundation (HRZZ) under the projects IP-2013-11- 1108, IP-2018-01-3168. [1] J. Jurec, B. Rakvin, M. Jokić, M. Kveder, J. Non- Cryst. Solids, 471 (2017), 435.

Using specific pulse sequences in ESR experiments, we have studied the differences between glassy and crystalline realization of the same material with the aim of finding a suitable experimental parameter for describing the disorder in glassy systems. The aim of our work is to contribute to the understanding of the influence of the disorder on the dynamic effects observed in glass at low temperatures for which a theoretical description has not been agreed upon yet. Focusing on a constant- time version of the Carr-Purcell-Meiboom-Gill (CPMG) pulse sequences, we studied two model systems: ethanol doped with nitroxyl radical TEMPO and γ- irradiated trehalose. Both materials were studied in glassy and polycrystalline state. We studied the hyperfine interaction of the electron spin with the spins of the matrix protons as a function of disorder ; i.e. molecular packing. In the case of ethanol, nuclear spectral diffusion (NSD) proved to be a dominant mechanism of the phase decoherence of electron spins [1], while in the case of trehalose, along with NSD, we have detected additional relaxation mechanisms that are supposed to derive from the electron- electron spin dipolar interaction between different radicals in the sample. The obtained experimental data are the basis for further theoretical studies of the molecular dynamics models in a disordered material since dynamic properties of nuclear spins (NSD), which are detected through the hyperfine interaction, directly reflect properties of the observed material.

Glassy and crystalline solid ethanol are used as a model systems to study disorder in the material. It is probed by the hyperfine interaction of the electron spin from the incorporated paramagnetic nitroxyl radical TEMPO. Nuclear spectral diffusion from host matrix protons is the dominant mechanism of electron spin decoherence of TEMPO incorporated in two realizations of solid-state environment of ethanol and it is proposed as a descriptor of the extent of disorder present in the system [1, 2]. It can be suppressed when applying special multiple-pulse sequence developed for the dynamical decoupling control of the central spin. The effect is much more pronounced in glassy than crystalline ethanol, the state exhibiting larger disorder/frustration. Since the phase memory relaxation time of the paramagnetic center increased linearly with the increase in the number of the applied refocusing pulses, the effect of the extent of disorder could be described numerically for this specific model system

Constant time Carr-Purcell-Meiboom-Gill (CPMG) pulse sequences were applied to two systems, ethanol doped with nitroxyl radical TEMPO and gamma-irradiated trehalose. The aim was to investigate the effect of different electron spin relaxation mechanisms in different systems on the efficiency of the preservation of the phase memory relaxation time T_m by dynamical decoupling and to test whether CPMG sequences can be used to discriminate them. In the case of ethanol, paramagnetic nitroxyl radical TEMPO was applied in the concentration range 0.2-1.1 mM. Trehalose samples were irradiated using X- ray radiation with standard dosages of 5-10 kGy. For both model systems, the measurements on glassy and crystalline type of samples were conducted to investigate impact of disorder as well. For ethanol no dependence of T_m on the concentration of paramagnetic centres and on the length of the used refocusing pulses was observed, implying nuclear spectral diffusion (NSD) as the dominant mechanism of electron spin decoherence [1]. Contrary to the observations in ethanol, no stretched exponential decay was observed when determining T_m in trehalose. In ethanol there was linear increase of T_m with number n of used refocusing pulses in the CPMG sequence. In trehalose the increase of T_m with n was not linear, the saturation effects observed for n≥4, which suggests that NSD isn’t the dominant mechanism of electron spin decoherence. The impact of instantaneous diffusion (ID) in trehalose is supported by the calculation of the concentration of radicals [2]. In conclusion, the efficiency of dynamical decoupling using constant time CPMG experiment strongly depends on the dominant mechanism of electron spin decoherence, therefore it can be used to determine whether NSD or ID is the dominant mechanism of decoherence.

Glassy and crystalline solid ethanol are used as a model systems to study disorder in the material. It is probed by the hyperfine interaction of the electron spin from the incorporated paramagnetic nitroxyl radical TEMPO. Nuclear spectral diffusion from host matrix protons is the dominant mechanism of electron spin decoherence of TEMPO incorporated in two realizations of solid-state environment of ethanol and it is proposed as a descriptor of the extent of disorder present in the system [1, 2]. It can be suppressed when applying special multiple-pulse sequence developed for the dynamical decoupling control of the central spin. The effect is much more pronounced in glassy than crystalline ethanol, the state exhibiting larger disorder/frustration. Since the phase memory relaxation time of the paramagnetic center increased linearly with the increase in the number of the applied refocusing pulses, the effect of the extent of disorder could be described numerically for this specific model system. [1] M. Kveder, D. Merunka, M. Jokić, B. Rakvin, J. Non-Cryst. Solids 354 (2008) 5201 [2] M. Kveder, B. Rakvin, M. Jokić, E. Reijerse, J. Non-Cryst. Solids 414 (2015) 27

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