Gajski, Goran

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Wells-Dawson polioksovolframati supstituisani hafnijumom kao potencijalna kontrastna sredstva: uticaj na DNK in vitro

Čolović, Mirjana; Gajski, Goran; Gerić, M.; Domijan, Ana-Marija; Savić, N.; Parac-Vogt, Tatjana; Krstić, Danijela

(Belgrade : Serbian Society of Toxicology, 2023)

TY  - CONF
AU  - Čolović, Mirjana
AU  - Gajski, Goran
AU  - Gerić, M.
AU  - Domijan, Ana-Marija
AU  - Savić, N.
AU  - Parac-Vogt, Tatjana
AU  - Krstić, Danijela
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12929
AB  - UVOD: Istraživanja pokazuju da su metalne nanočestice pogodni kandidati za kontrastna sredstva
(CESA-contrast-enhancing staining agents) nove generacije za kompjuterizovanu tomografiju (CT)
zahvaljujući velikoj gustini i sposobnosti da apsorbuju X-zrake.
CILJ: Studije toksičnosti in vivo ukazuju na štetno dejstvo polioksometalata, što bi mogla biti glavna
prepreka u kliničkoj primeni ovih bioaktivnih kompleksnih jedinjenja. Stoga je cilj ovog istraživanja da
se ispitaju genotoksične osobine polioksovolframata Wells-Dawson tipa supstituisanih sa hafnijumom
(Hf-WD 1:2), K16[Hf(α2-P2W17O61)2]·19H2O, koji je pokazao dobre osobine kao kontrastno sredstvo za
vizuelizaciju tkiva bubrega i dugih kostiju miša.
METODOLOGIJA: Hf-WD 1:2 je sintetisan prema metodi opisanoj u literaturi. Uzorci humane pune krvi
su uzeti od zdravih donora i izloženi različitim koncentracijama (10-6-10-4 mol/L) Hf-WD 1:2 tokom 4
i 24 sata, na 37 °C. Standardna metoda za alkalni komet test je korišćena za praćenje genotoksičnih
efekata Hf-WD 1:2.
REZULTATI: Stepen oštećenja DNK humane periferne krvi nakon izlaganja Hf-WD 1:2 je izražen kao relativno
povećanje repne DNK u odnosu na kontrolu. Nije uočena statistički značajna razlika u količini prekida
DNK lanca u poređenju sa odgovarajućom kontrolom, za oba vremena izlaganja (4 i 24 sata) i za sve
ispitivane koncentracije polioksovolframata.
ZAKLJUČAK: In vitro ispitivanje genotoksičnosti pokazalo je da Hf-WD 1:2 ne menja značajno strukturu
DNK zdravih humanih ćelija pune krvi i stoga se može smatrati bezbednim u smislu genotoksičnosti u
dodatnim studijama kao potencijalnog kontrastnog sredstva za CT.
AB  - INTRODUCTION: Metallic nanoparticles have been reported as promising candidates for the development
of new-generation contrast-enhancing staining agents (CESAs) for computed tomography (CT)
due to their high X-ray attenuation and density.
AIM: In vivo toxicity studies revealed side effects of polyoxometalate clusters, which could be a key
obstacle in the potential clinical application of these bioactive compounds. Therefore, the aim of this
investigation was to perform the genotoxicity evaluation of 1:2 hafnium(IV)-substituted Wells-Dawson
polyoxotungstate (Hf-WD 1:2), K16[Hf(α2-P2W17O61)2]·19H2O that was reported as a promising CESA
candidate to visualize murine long bones and kidneys.
METHODOLOGY: Hf-WD 1:2 was prepared using the method described in the literature. Human whole
blood samples were taken from healthy donors and exposed to different Hf-WD 1:2 concentrations
(within the range of 10-6-10-4 mol/L) for 4 and 24 h, at 37 °C. The standard procedure for alkaline comet
assay was carried out for monitoring the genotoxic effects of Hf-WD 1:2.
RESULTS: The degree of DNA damage in human peripheral blood cells after exposure to Hf-WD 1:2 was
expressed as a relative increase of tail DNA related to the control. No statistically significant difference
in the amount of DNA strand breaks in comparison with the corresponding control was observed for
both 4 and 24 h, regardless of the Hf-WD 1:2 concentrations tested.
CONCLUSION: In vitro genotoxicity assessment indicated that Hf-WD 1:2 does not affect DNA structure
in healthy human blood cells, accordingly might be regarded as genotoxicity safe in further research as
a potential CESA for CT.
PB  - Belgrade : Serbian Society of Toxicology
C3  - 13th International Congress of the Serbian Society of Toxicology and the 1st ToxSEE Regional Conference : Abstract book
T1  - Wells-Dawson polioksovolframati supstituisani hafnijumom kao potencijalna kontrastna sredstva: uticaj na DNK in vitro
T1  - Hafnium(IV)-substituted Wells-Dawson based contrast-enhancing staining agent: effect on DNA in vitro
SP  - 189
EP  - 190
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12929
ER  - 
@conference{
author = "Čolović, Mirjana and Gajski, Goran and Gerić, M. and Domijan, Ana-Marija and Savić, N. and Parac-Vogt, Tatjana and Krstić, Danijela",
year = "2023",
abstract = "UVOD: Istraživanja pokazuju da su metalne nanočestice pogodni kandidati za kontrastna sredstva
(CESA-contrast-enhancing staining agents) nove generacije za kompjuterizovanu tomografiju (CT)
zahvaljujući velikoj gustini i sposobnosti da apsorbuju X-zrake.
CILJ: Studije toksičnosti in vivo ukazuju na štetno dejstvo polioksometalata, što bi mogla biti glavna
prepreka u kliničkoj primeni ovih bioaktivnih kompleksnih jedinjenja. Stoga je cilj ovog istraživanja da
se ispitaju genotoksične osobine polioksovolframata Wells-Dawson tipa supstituisanih sa hafnijumom
(Hf-WD 1:2), K16[Hf(α2-P2W17O61)2]·19H2O, koji je pokazao dobre osobine kao kontrastno sredstvo za
vizuelizaciju tkiva bubrega i dugih kostiju miša.
METODOLOGIJA: Hf-WD 1:2 je sintetisan prema metodi opisanoj u literaturi. Uzorci humane pune krvi
su uzeti od zdravih donora i izloženi različitim koncentracijama (10-6-10-4 mol/L) Hf-WD 1:2 tokom 4
i 24 sata, na 37 °C. Standardna metoda za alkalni komet test je korišćena za praćenje genotoksičnih
efekata Hf-WD 1:2.
REZULTATI: Stepen oštećenja DNK humane periferne krvi nakon izlaganja Hf-WD 1:2 je izražen kao relativno
povećanje repne DNK u odnosu na kontrolu. Nije uočena statistički značajna razlika u količini prekida
DNK lanca u poređenju sa odgovarajućom kontrolom, za oba vremena izlaganja (4 i 24 sata) i za sve
ispitivane koncentracije polioksovolframata.
ZAKLJUČAK: In vitro ispitivanje genotoksičnosti pokazalo je da Hf-WD 1:2 ne menja značajno strukturu
DNK zdravih humanih ćelija pune krvi i stoga se može smatrati bezbednim u smislu genotoksičnosti u
dodatnim studijama kao potencijalnog kontrastnog sredstva za CT., INTRODUCTION: Metallic nanoparticles have been reported as promising candidates for the development
of new-generation contrast-enhancing staining agents (CESAs) for computed tomography (CT)
due to their high X-ray attenuation and density.
AIM: In vivo toxicity studies revealed side effects of polyoxometalate clusters, which could be a key
obstacle in the potential clinical application of these bioactive compounds. Therefore, the aim of this
investigation was to perform the genotoxicity evaluation of 1:2 hafnium(IV)-substituted Wells-Dawson
polyoxotungstate (Hf-WD 1:2), K16[Hf(α2-P2W17O61)2]·19H2O that was reported as a promising CESA
candidate to visualize murine long bones and kidneys.
METHODOLOGY: Hf-WD 1:2 was prepared using the method described in the literature. Human whole
blood samples were taken from healthy donors and exposed to different Hf-WD 1:2 concentrations
(within the range of 10-6-10-4 mol/L) for 4 and 24 h, at 37 °C. The standard procedure for alkaline comet
assay was carried out for monitoring the genotoxic effects of Hf-WD 1:2.
RESULTS: The degree of DNA damage in human peripheral blood cells after exposure to Hf-WD 1:2 was
expressed as a relative increase of tail DNA related to the control. No statistically significant difference
in the amount of DNA strand breaks in comparison with the corresponding control was observed for
both 4 and 24 h, regardless of the Hf-WD 1:2 concentrations tested.
CONCLUSION: In vitro genotoxicity assessment indicated that Hf-WD 1:2 does not affect DNA structure
in healthy human blood cells, accordingly might be regarded as genotoxicity safe in further research as
a potential CESA for CT.",
publisher = "Belgrade : Serbian Society of Toxicology",
journal = "13th International Congress of the Serbian Society of Toxicology and the 1st ToxSEE Regional Conference : Abstract book",
title = "Wells-Dawson polioksovolframati supstituisani hafnijumom kao potencijalna kontrastna sredstva: uticaj na DNK in vitro, Hafnium(IV)-substituted Wells-Dawson based contrast-enhancing staining agent: effect on DNA in vitro",
pages = "189-190",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12929"
}
Čolović, M., Gajski, G., Gerić, M., Domijan, A., Savić, N., Parac-Vogt, T.,& Krstić, D.. (2023). Wells-Dawson polioksovolframati supstituisani hafnijumom kao potencijalna kontrastna sredstva: uticaj na DNK in vitro. in 13th International Congress of the Serbian Society of Toxicology and the 1st ToxSEE Regional Conference : Abstract book
Belgrade : Serbian Society of Toxicology., 189-190.
https://hdl.handle.net/21.15107/rcub_vinar_12929
Čolović M, Gajski G, Gerić M, Domijan A, Savić N, Parac-Vogt T, Krstić D. Wells-Dawson polioksovolframati supstituisani hafnijumom kao potencijalna kontrastna sredstva: uticaj na DNK in vitro. in 13th International Congress of the Serbian Society of Toxicology and the 1st ToxSEE Regional Conference : Abstract book. 2023;:189-190.
https://hdl.handle.net/21.15107/rcub_vinar_12929 .
Čolović, Mirjana, Gajski, Goran, Gerić, M., Domijan, Ana-Marija, Savić, N., Parac-Vogt, Tatjana, Krstić, Danijela, "Wells-Dawson polioksovolframati supstituisani hafnijumom kao potencijalna kontrastna sredstva: uticaj na DNK in vitro" in 13th International Congress of the Serbian Society of Toxicology and the 1st ToxSEE Regional Conference : Abstract book (2023):189-190,
https://hdl.handle.net/21.15107/rcub_vinar_12929 .

Evaluacija genotoksičnosti nanoklastera polioksovolframata kao potencijalnog kontrastnog agensa

Čolović, Mirjana; Gajski, Goran; Gerić, M.; Domijan, Ana-Marija; Savić, N.; Parac-Vogt, Tatjana; Krstić, Danijela

(Belgrade : Serbian Society of Toxicology, 2023)

TY  - CONF
AU  - Čolović, Mirjana
AU  - Gajski, Goran
AU  - Gerić, M.
AU  - Domijan, Ana-Marija
AU  - Savić, N.
AU  - Parac-Vogt, Tatjana
AU  - Krstić, Danijela
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12930
AB  - UVOD: Polioksovolframati su negativno naelektrisana neorganska kompleksna jedinjenja koja se dve
decenije intenzivno proučavaju kao moćni bioaktivni agensi. Skorašnje studije na dugim kostima i
bubrezima miša su pokazale da poliokosvoframati mogu da se koriste kao agensi za bojenje za poboljšanje
kontrasta (CESAs) za kompjuterizovanu tomografiju (CT).
CILJ: S obzirom da razvoj novih medicinskih agenasa zahteva procenu njihove bezbednosti, cilj ove
studije je da se evaluiraju genotoksične osobine in vitro polioksovolframata Wells-Dawson tipa (parent
WD), α2-K6P2W18O62.14H2O, koji je u prethodnim istraživanjima pokazao bolje osobine u odnosu na
joheksol, standardni kontrastni agens za CT.
METODOLOGIJA: Parent WD je sintetisan sledeći ovjavljenu proceduru. Uzorci humane krvi dobijeni od
zdravih donora su tretirani ispitivanim polioksovolframatom, a zatim inkubirani na 37 °C tokom 4 i 24
sata. Za procenu genotoksičnosti parent WD korišćen je alkalni komet test kako je opisano u literaturi.
REZULTATI: Uzorci pune krvi su tretirani parent WD polioksovolframatom u opsegu koncentracija
1-100 μmol/L. Oštećenje DNK, koje se koristi kao pokazatelj genotoksičnosti, je izraženo kao % repne
DNK. Dobijeni rezultati su pokazali da sve ispitivane koncentracije parent WD nisu značajno uticale na
oštećenje DNK u odnosu na odgovarajuću kontrolu, posle 4 i 24 sata tretmana.
ZAKLJUČAK: Parent WD nanoklaster nije izazvao genotoksični efekat na zdravim ćelijama periferne
humane krvi u svim ispitivanim koncentracijama. U skladu sa tim, ispitivani potencijalni CESA kandidat
za CT bi se u daljim istraživanjima mogao smatrati bezbednim sa stanovišta genotoksičnosti.
AB  - INTRODUCTION: Polyoxotungstates are negatively charged inorganic cage complexes that were studied
as potent bioactive agents for the last two decades. They were recently reported as promising
contrast-enhancing staining agents (CESAs) for computed tomography (CT) of murine long bones and
kidney tissues.
AIM: Taking into account the fact that the development of novel medications requires an evaluation
of their safety, the purpose of this study was to assess the genotoxic properties in vitro of parent
Wells-Dawson polyoxotungstate (parent WD), α2-K6P2W18O62.14H2O that showed superior imaging
capabilities compared to the standard CT contrast agent iohexol.
METHODOLOGY: Parent WD was synthesized according to the published procedure. Human whole
blood samples obtained from healthy donors were treated with parent WD, and then incubated at 37
°C for 4 and 24 h. For the genotoxicity assessment of the studied nanocluster alkaline comet assay was
performed as described in the literature.
RESULTS: Whole blood samples were treated with parent WD within the concentration range of 1-100
μmol/L. DNA damage was expressed as % of tail DNA and used as the indicator of genotoxicity. The
obtained results demonstrated that parent WD at all investigated concentrations did not significantly
affect DNA damage with respect to the corresponding control, for both 4 and 24 h.
CONCLUSION: Parent WD nanocluster did not induce a genotoxic effect on normal non-target human
peripheral blood cells at all studied concentrations. Thus, this promising CESA candidate for CT could
be considered in further research as safe from a genotoxicity point of view.
PB  - Belgrade : Serbian Society of Toxicology
C3  - 13th International Congress of the Serbian Society of Toxicology and the 1st ToxSEE Regional Conference : Abstract book
T1  - Evaluacija genotoksičnosti nanoklastera polioksovolframata kao potencijalnog kontrastnog agensa
T1  - Genotoxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent
SP  - 191
EP  - 192
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12930
ER  - 
@conference{
author = "Čolović, Mirjana and Gajski, Goran and Gerić, M. and Domijan, Ana-Marija and Savić, N. and Parac-Vogt, Tatjana and Krstić, Danijela",
year = "2023",
abstract = "UVOD: Polioksovolframati su negativno naelektrisana neorganska kompleksna jedinjenja koja se dve
decenije intenzivno proučavaju kao moćni bioaktivni agensi. Skorašnje studije na dugim kostima i
bubrezima miša su pokazale da poliokosvoframati mogu da se koriste kao agensi za bojenje za poboljšanje
kontrasta (CESAs) za kompjuterizovanu tomografiju (CT).
CILJ: S obzirom da razvoj novih medicinskih agenasa zahteva procenu njihove bezbednosti, cilj ove
studije je da se evaluiraju genotoksične osobine in vitro polioksovolframata Wells-Dawson tipa (parent
WD), α2-K6P2W18O62.14H2O, koji je u prethodnim istraživanjima pokazao bolje osobine u odnosu na
joheksol, standardni kontrastni agens za CT.
METODOLOGIJA: Parent WD je sintetisan sledeći ovjavljenu proceduru. Uzorci humane krvi dobijeni od
zdravih donora su tretirani ispitivanim polioksovolframatom, a zatim inkubirani na 37 °C tokom 4 i 24
sata. Za procenu genotoksičnosti parent WD korišćen je alkalni komet test kako je opisano u literaturi.
REZULTATI: Uzorci pune krvi su tretirani parent WD polioksovolframatom u opsegu koncentracija
1-100 μmol/L. Oštećenje DNK, koje se koristi kao pokazatelj genotoksičnosti, je izraženo kao % repne
DNK. Dobijeni rezultati su pokazali da sve ispitivane koncentracije parent WD nisu značajno uticale na
oštećenje DNK u odnosu na odgovarajuću kontrolu, posle 4 i 24 sata tretmana.
ZAKLJUČAK: Parent WD nanoklaster nije izazvao genotoksični efekat na zdravim ćelijama periferne
humane krvi u svim ispitivanim koncentracijama. U skladu sa tim, ispitivani potencijalni CESA kandidat
za CT bi se u daljim istraživanjima mogao smatrati bezbednim sa stanovišta genotoksičnosti., INTRODUCTION: Polyoxotungstates are negatively charged inorganic cage complexes that were studied
as potent bioactive agents for the last two decades. They were recently reported as promising
contrast-enhancing staining agents (CESAs) for computed tomography (CT) of murine long bones and
kidney tissues.
AIM: Taking into account the fact that the development of novel medications requires an evaluation
of their safety, the purpose of this study was to assess the genotoxic properties in vitro of parent
Wells-Dawson polyoxotungstate (parent WD), α2-K6P2W18O62.14H2O that showed superior imaging
capabilities compared to the standard CT contrast agent iohexol.
METHODOLOGY: Parent WD was synthesized according to the published procedure. Human whole
blood samples obtained from healthy donors were treated with parent WD, and then incubated at 37
°C for 4 and 24 h. For the genotoxicity assessment of the studied nanocluster alkaline comet assay was
performed as described in the literature.
RESULTS: Whole blood samples were treated with parent WD within the concentration range of 1-100
μmol/L. DNA damage was expressed as % of tail DNA and used as the indicator of genotoxicity. The
obtained results demonstrated that parent WD at all investigated concentrations did not significantly
affect DNA damage with respect to the corresponding control, for both 4 and 24 h.
CONCLUSION: Parent WD nanocluster did not induce a genotoxic effect on normal non-target human
peripheral blood cells at all studied concentrations. Thus, this promising CESA candidate for CT could
be considered in further research as safe from a genotoxicity point of view.",
publisher = "Belgrade : Serbian Society of Toxicology",
journal = "13th International Congress of the Serbian Society of Toxicology and the 1st ToxSEE Regional Conference : Abstract book",
title = "Evaluacija genotoksičnosti nanoklastera polioksovolframata kao potencijalnog kontrastnog agensa, Genotoxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent",
pages = "191-192",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12930"
}
Čolović, M., Gajski, G., Gerić, M., Domijan, A., Savić, N., Parac-Vogt, T.,& Krstić, D.. (2023). Evaluacija genotoksičnosti nanoklastera polioksovolframata kao potencijalnog kontrastnog agensa. in 13th International Congress of the Serbian Society of Toxicology and the 1st ToxSEE Regional Conference : Abstract book
Belgrade : Serbian Society of Toxicology., 191-192.
https://hdl.handle.net/21.15107/rcub_vinar_12930
Čolović M, Gajski G, Gerić M, Domijan A, Savić N, Parac-Vogt T, Krstić D. Evaluacija genotoksičnosti nanoklastera polioksovolframata kao potencijalnog kontrastnog agensa. in 13th International Congress of the Serbian Society of Toxicology and the 1st ToxSEE Regional Conference : Abstract book. 2023;:191-192.
https://hdl.handle.net/21.15107/rcub_vinar_12930 .
Čolović, Mirjana, Gajski, Goran, Gerić, M., Domijan, Ana-Marija, Savić, N., Parac-Vogt, Tatjana, Krstić, Danijela, "Evaluacija genotoksičnosti nanoklastera polioksovolframata kao potencijalnog kontrastnog agensa" in 13th International Congress of the Serbian Society of Toxicology and the 1st ToxSEE Regional Conference : Abstract book (2023):191-192,
https://hdl.handle.net/21.15107/rcub_vinar_12930 .

In vitro toxicity evaluation of potential contrast agents for micro-computed tomography: effect on cell membrane

Domijan, Ana-Marija; Gajski, Goran; Gerić, M.; Savić, Nada; Parac-Vogt, Tatjana; Krstić, Danijela; Čolović, Mirjana

(Belgrade : Society of Physical Chemists of Serbia, 2022)

TY  - CONF
AU  - Domijan, Ana-Marija
AU  - Gajski, Goran
AU  - Gerić, M.
AU  - Savić, Nada
AU  - Parac-Vogt, Tatjana
AU  - Krstić, Danijela
AU  - Čolović, Mirjana
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12926
AB  - In this study, prooxidative properties of three Wells-Dawson polyoxometalates (POMs) previously reported as promising contrast-enhancing staining agents for micro-computed tomography (microCT): parent Wells-Dawson POM α2-K6P2W18O62.14H2O (parent WD), monolacunary Wells-Dawson POM α2-K10P2W17O61.20H2O (lacunary WD), and 1:2 hafnium(IV)-substituted Wells-Dawson POM K16[Hf(α2-P2W17O61)2]·19H2O (Hf-WD 1:2), were evaluated in vitro. In this aim, malondialdehyde (MDA) level, as an indicator of prooxidant action and lipid peroxidation, was determined in human plasma after 24 h treatment with the POMs in the concentration range 1-100 μM at 37 °C. The results demonstrated that the studied POMs did not induce an increase in plasma lipid peroxidation level compared to the corresponding control. Thus, it could be concluded that the investigated POM-based contrast agent candidates for microCT are not sufficiently potent prooxidants capable to cause membrane damage and consequent toxic occurrences.
PB  - Belgrade : Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2022 : 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry : Proceedings
T1  - In vitro toxicity evaluation of potential contrast agents for micro-computed tomography: effect on cell membrane
VL  - 1
SP  - 283
EP  - 286
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12926
ER  - 
@conference{
author = "Domijan, Ana-Marija and Gajski, Goran and Gerić, M. and Savić, Nada and Parac-Vogt, Tatjana and Krstić, Danijela and Čolović, Mirjana",
year = "2022",
abstract = "In this study, prooxidative properties of three Wells-Dawson polyoxometalates (POMs) previously reported as promising contrast-enhancing staining agents for micro-computed tomography (microCT): parent Wells-Dawson POM α2-K6P2W18O62.14H2O (parent WD), monolacunary Wells-Dawson POM α2-K10P2W17O61.20H2O (lacunary WD), and 1:2 hafnium(IV)-substituted Wells-Dawson POM K16[Hf(α2-P2W17O61)2]·19H2O (Hf-WD 1:2), were evaluated in vitro. In this aim, malondialdehyde (MDA) level, as an indicator of prooxidant action and lipid peroxidation, was determined in human plasma after 24 h treatment with the POMs in the concentration range 1-100 μM at 37 °C. The results demonstrated that the studied POMs did not induce an increase in plasma lipid peroxidation level compared to the corresponding control. Thus, it could be concluded that the investigated POM-based contrast agent candidates for microCT are not sufficiently potent prooxidants capable to cause membrane damage and consequent toxic occurrences.",
publisher = "Belgrade : Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2022 : 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry : Proceedings",
title = "In vitro toxicity evaluation of potential contrast agents for micro-computed tomography: effect on cell membrane",
volume = "1",
pages = "283-286",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12926"
}
Domijan, A., Gajski, G., Gerić, M., Savić, N., Parac-Vogt, T., Krstić, D.,& Čolović, M.. (2022). In vitro toxicity evaluation of potential contrast agents for micro-computed tomography: effect on cell membrane. in PHYSICAL CHEMISTRY 2022 : 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry : Proceedings
Belgrade : Society of Physical Chemists of Serbia., 1, 283-286.
https://hdl.handle.net/21.15107/rcub_vinar_12926
Domijan A, Gajski G, Gerić M, Savić N, Parac-Vogt T, Krstić D, Čolović M. In vitro toxicity evaluation of potential contrast agents for micro-computed tomography: effect on cell membrane. in PHYSICAL CHEMISTRY 2022 : 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry : Proceedings. 2022;1:283-286.
https://hdl.handle.net/21.15107/rcub_vinar_12926 .
Domijan, Ana-Marija, Gajski, Goran, Gerić, M., Savić, Nada, Parac-Vogt, Tatjana, Krstić, Danijela, Čolović, Mirjana, "In vitro toxicity evaluation of potential contrast agents for micro-computed tomography: effect on cell membrane" in PHYSICAL CHEMISTRY 2022 : 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry : Proceedings, 1 (2022):283-286,
https://hdl.handle.net/21.15107/rcub_vinar_12926 .

Cytotoxicity evaluation of promising staining agents for contrast-enhanced microfocus computed tomography

Čolović, Mirjana; Gajski, Goran; Gerić, M.; Savić, Nada; Krstić, Danijela

(Belgrade : Society of Physical Chemists of Serbia, 2022)

TY  - CONF
AU  - Čolović, Mirjana
AU  - Gajski, Goran
AU  - Gerić, M.
AU  - Savić, Nada
AU  - Krstić, Danijela
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12924
AB  - Cytotoxicity assessment in vitro of three Wells-Dawson polyoxometalates (POMs) as contrast-enhancing staining agent (CESA) candidates: parent Wells-Dawson POM α2-K6P2W18O62.14H2O (parent WD), monolacunary Wells-Dawson POM α2-K10P2W17O61.20H2O (lacunary WD), and 1:2 hafnium(IV)-substituted Wells-Dawson POM K16[Hf(α2-P2W17O61)2]·19H2O (Hf-WD 1:2), was carried out on healthy non-target human blood cells. Whole blood samples were treated with these POMs (1-100 μM) for 4 and 24 h at 37 °C. The results showed a time-dependent decrease of the peripheral blood mononuclear cell (PBMC) viability for all investigated polyoxotungstates. The 4 h treatment induced a significant cytotoxic effect only for the higher concentrations of Hf-WD 1:2, whereas 24 h exposure resulted in a concentration-dependent alteration of the cell viability. The most potent cytotoxic activity was obtained for Hf-WD 1:2 inducing a decrease of the cell viability from 25 to 45% compared to the corresponding control. The weakest effect was observed for parent WD, which resulted in no statistically significant difference in PBMC viability in respect to the control at the concentration of 1 μM. Finally, parent WD, lacunary WD, and Hf-WD 1:2 could not be considered safe from a cytotoxic point of view, thus further more extensive toxicity studies are needed.
PB  - Belgrade : Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2022 : 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry : Proceedings
T1  - Cytotoxicity evaluation of promising staining agents for contrast-enhanced microfocus computed tomography
VL  - 1
SP  - 275
EP  - 278
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12924
ER  - 
@conference{
author = "Čolović, Mirjana and Gajski, Goran and Gerić, M. and Savić, Nada and Krstić, Danijela",
year = "2022",
abstract = "Cytotoxicity assessment in vitro of three Wells-Dawson polyoxometalates (POMs) as contrast-enhancing staining agent (CESA) candidates: parent Wells-Dawson POM α2-K6P2W18O62.14H2O (parent WD), monolacunary Wells-Dawson POM α2-K10P2W17O61.20H2O (lacunary WD), and 1:2 hafnium(IV)-substituted Wells-Dawson POM K16[Hf(α2-P2W17O61)2]·19H2O (Hf-WD 1:2), was carried out on healthy non-target human blood cells. Whole blood samples were treated with these POMs (1-100 μM) for 4 and 24 h at 37 °C. The results showed a time-dependent decrease of the peripheral blood mononuclear cell (PBMC) viability for all investigated polyoxotungstates. The 4 h treatment induced a significant cytotoxic effect only for the higher concentrations of Hf-WD 1:2, whereas 24 h exposure resulted in a concentration-dependent alteration of the cell viability. The most potent cytotoxic activity was obtained for Hf-WD 1:2 inducing a decrease of the cell viability from 25 to 45% compared to the corresponding control. The weakest effect was observed for parent WD, which resulted in no statistically significant difference in PBMC viability in respect to the control at the concentration of 1 μM. Finally, parent WD, lacunary WD, and Hf-WD 1:2 could not be considered safe from a cytotoxic point of view, thus further more extensive toxicity studies are needed.",
publisher = "Belgrade : Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2022 : 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry : Proceedings",
title = "Cytotoxicity evaluation of promising staining agents for contrast-enhanced microfocus computed tomography",
volume = "1",
pages = "275-278",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12924"
}
Čolović, M., Gajski, G., Gerić, M., Savić, N.,& Krstić, D.. (2022). Cytotoxicity evaluation of promising staining agents for contrast-enhanced microfocus computed tomography. in PHYSICAL CHEMISTRY 2022 : 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry : Proceedings
Belgrade : Society of Physical Chemists of Serbia., 1, 275-278.
https://hdl.handle.net/21.15107/rcub_vinar_12924
Čolović M, Gajski G, Gerić M, Savić N, Krstić D. Cytotoxicity evaluation of promising staining agents for contrast-enhanced microfocus computed tomography. in PHYSICAL CHEMISTRY 2022 : 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry : Proceedings. 2022;1:275-278.
https://hdl.handle.net/21.15107/rcub_vinar_12924 .
Čolović, Mirjana, Gajski, Goran, Gerić, M., Savić, Nada, Krstić, Danijela, "Cytotoxicity evaluation of promising staining agents for contrast-enhanced microfocus computed tomography" in PHYSICAL CHEMISTRY 2022 : 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry : Proceedings, 1 (2022):275-278,
https://hdl.handle.net/21.15107/rcub_vinar_12924 .

Prooxidative properties of contrast agent candidates for micro-computed tomography

Čolović, Mirjana; Domijan, Ana-Marija; Gajski, Goran; Gerić, M.; Parac-Vogt, Tatjana; Krstić, Danijela

(Belgrade : Society of Physical Chemists of Serbia, 2022)

TY  - CONF
AU  - Čolović, Mirjana
AU  - Domijan, Ana-Marija
AU  - Gajski, Goran
AU  - Gerić, M.
AU  - Parac-Vogt, Tatjana
AU  - Krstić, Danijela
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12925
AB  - The aim of this study to assess in vitro prooxidative properties of three polyoxometalate (POM)-based species that were found as potential contrast-enhancing staining agents for micro-computed tomography (microCT) to visualize kidney and bone tissues: parent Wells-Dawson POM α2-K6P2W18O62.14H2O (parent WD), monolacunary Wells-Dawson POM α2-K10P2W17O61.20H2O (lacunary WD), and 1:2 hafnium(IV)-substituted Wells-Dawson POM K16[Hf(α2-P2W17O61)2]·19H2O (Hf-WD 1:2). Thus, reduced glutathione (GSH) concentration, as a major antioxidant to prevent reactive oxygen species (ROS) attack and an indicator of oxidative stress, was followed in human plasma after 24 h exposure to the POMs within the concentration range 1-100 μM at 37 °C. The promising contrast agents exhibited various prooxidative properties. Parent WD did not significantly influence GSH level, thus prooxidative properties could not be associated with this POM species. On the contrary, Hf-WD 1:2 exposure resulted in a significant decrease in GSH concentration in human plasma compared to untreated control. Accordingly, Hf-WD 1:2 might be regarded as a prooxidant agent that could cause oxidative stress and consequent toxic occurrences. Nevertheless, additional studies on other relevant oxidative stress parameters are needed to confirm this assumption.
PB  - Belgrade : Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2022 : 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry : Proceedings
T1  - Prooxidative properties of contrast agent candidates for micro-computed tomography
VL  - 1
SP  - 279
EP  - 282
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12925
ER  - 
@conference{
author = "Čolović, Mirjana and Domijan, Ana-Marija and Gajski, Goran and Gerić, M. and Parac-Vogt, Tatjana and Krstić, Danijela",
year = "2022",
abstract = "The aim of this study to assess in vitro prooxidative properties of three polyoxometalate (POM)-based species that were found as potential contrast-enhancing staining agents for micro-computed tomography (microCT) to visualize kidney and bone tissues: parent Wells-Dawson POM α2-K6P2W18O62.14H2O (parent WD), monolacunary Wells-Dawson POM α2-K10P2W17O61.20H2O (lacunary WD), and 1:2 hafnium(IV)-substituted Wells-Dawson POM K16[Hf(α2-P2W17O61)2]·19H2O (Hf-WD 1:2). Thus, reduced glutathione (GSH) concentration, as a major antioxidant to prevent reactive oxygen species (ROS) attack and an indicator of oxidative stress, was followed in human plasma after 24 h exposure to the POMs within the concentration range 1-100 μM at 37 °C. The promising contrast agents exhibited various prooxidative properties. Parent WD did not significantly influence GSH level, thus prooxidative properties could not be associated with this POM species. On the contrary, Hf-WD 1:2 exposure resulted in a significant decrease in GSH concentration in human plasma compared to untreated control. Accordingly, Hf-WD 1:2 might be regarded as a prooxidant agent that could cause oxidative stress and consequent toxic occurrences. Nevertheless, additional studies on other relevant oxidative stress parameters are needed to confirm this assumption.",
publisher = "Belgrade : Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2022 : 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry : Proceedings",
title = "Prooxidative properties of contrast agent candidates for micro-computed tomography",
volume = "1",
pages = "279-282",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12925"
}
Čolović, M., Domijan, A., Gajski, G., Gerić, M., Parac-Vogt, T.,& Krstić, D.. (2022). Prooxidative properties of contrast agent candidates for micro-computed tomography. in PHYSICAL CHEMISTRY 2022 : 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry : Proceedings
Belgrade : Society of Physical Chemists of Serbia., 1, 279-282.
https://hdl.handle.net/21.15107/rcub_vinar_12925
Čolović M, Domijan A, Gajski G, Gerić M, Parac-Vogt T, Krstić D. Prooxidative properties of contrast agent candidates for micro-computed tomography. in PHYSICAL CHEMISTRY 2022 : 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry : Proceedings. 2022;1:279-282.
https://hdl.handle.net/21.15107/rcub_vinar_12925 .
Čolović, Mirjana, Domijan, Ana-Marija, Gajski, Goran, Gerić, M., Parac-Vogt, Tatjana, Krstić, Danijela, "Prooxidative properties of contrast agent candidates for micro-computed tomography" in PHYSICAL CHEMISTRY 2022 : 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry : Proceedings, 1 (2022):279-282,
https://hdl.handle.net/21.15107/rcub_vinar_12925 .

Polyoxopalladates as potential antitumor drugs: in vitro toxicity assessment

Čolović, Mirjana; Gajski, Goran; Ma, Tian; Isaković, Anđelka; Misirlić-Denčić, Sonja; Kortz, Urlich; Krstić, Danijela

(Zagreb, Croatia : Institute for Medical Research and Occupational Health, 2021)

TY  - CONF
AU  - Čolović, Mirjana
AU  - Gajski, Goran
AU  - Ma, Tian
AU  - Isaković, Anđelka
AU  - Misirlić-Denčić, Sonja
AU  - Kortz, Urlich
AU  - Krstić, Danijela
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12963
AB  - Polyoxopalladates (POPs) are a subclass of polyoxometalates (POMs) comprising discrete, anionic palladium(II)-oxo complexes. Although numerous studies have been conducted on the biological activity of POMs, their toxicity (e.g. nonselectivity) is frequently a limitation for real-world biomedical applications. Thus, the aim of this study was to evaluate the in vitro safety of the three POPs Pd13 As8 , SrPd12 As6 , and Pd13 (PhAs)8 , which exhibited strong antitumour activity against human neuroblastoma cell line SH-SY5Y, by performing a cyto/genotoxicity study on human healthy blood. Blood samples obtained from a healthy female donor were treated with three different concentrations (12.5, 25, and 50 µmol/L) of the POPs, and incubated at 37 oC for 4 and 24 h. A cytotoxicity (cell viability) assay was performed on isolated human peripheral blood lymphocytes stained with acridine orange and ethidium bromide. A genotoxicity test was carried out on whole blood by alkaline comet assay (microgel electrophoresis), and the percentage of tail DNA was used to assess the level of DNA damage. Pd13 As8 did not affect neither cell viability nor DNA damage, related to the control, at either of the investigated concentrations (after both 4 and 24 h). On the contrary, higher concentrations (25 and 50 µmol/L) of both SrPd12 As6 and Pd13 (PhAs)8 induced a statistically significant decrease in cell viability after 24 h (up to 42 %), and a relative increase of tail DNA (up to 3×) was observed at 50 µmol/L, after 24 h. Therefore, Pd13 As8 could be regarded as non-toxic to human healthy cells, whereas SrPd12 As6 and Pd13 (PhAs)8 require additional toxicity analysis.
PB  - Zagreb, Croatia : Institute for Medical Research and Occupational Health
C3  - Archives of Industrial Hygiene and Toxicology
T1  - Polyoxopalladates as potential antitumor drugs: in vitro toxicity assessment
VL  - 72
IS  - Suppl. 1
SP  - 65
EP  - 65
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12963
ER  - 
@conference{
author = "Čolović, Mirjana and Gajski, Goran and Ma, Tian and Isaković, Anđelka and Misirlić-Denčić, Sonja and Kortz, Urlich and Krstić, Danijela",
year = "2021",
abstract = "Polyoxopalladates (POPs) are a subclass of polyoxometalates (POMs) comprising discrete, anionic palladium(II)-oxo complexes. Although numerous studies have been conducted on the biological activity of POMs, their toxicity (e.g. nonselectivity) is frequently a limitation for real-world biomedical applications. Thus, the aim of this study was to evaluate the in vitro safety of the three POPs Pd13 As8 , SrPd12 As6 , and Pd13 (PhAs)8 , which exhibited strong antitumour activity against human neuroblastoma cell line SH-SY5Y, by performing a cyto/genotoxicity study on human healthy blood. Blood samples obtained from a healthy female donor were treated with three different concentrations (12.5, 25, and 50 µmol/L) of the POPs, and incubated at 37 oC for 4 and 24 h. A cytotoxicity (cell viability) assay was performed on isolated human peripheral blood lymphocytes stained with acridine orange and ethidium bromide. A genotoxicity test was carried out on whole blood by alkaline comet assay (microgel electrophoresis), and the percentage of tail DNA was used to assess the level of DNA damage. Pd13 As8 did not affect neither cell viability nor DNA damage, related to the control, at either of the investigated concentrations (after both 4 and 24 h). On the contrary, higher concentrations (25 and 50 µmol/L) of both SrPd12 As6 and Pd13 (PhAs)8 induced a statistically significant decrease in cell viability after 24 h (up to 42 %), and a relative increase of tail DNA (up to 3×) was observed at 50 µmol/L, after 24 h. Therefore, Pd13 As8 could be regarded as non-toxic to human healthy cells, whereas SrPd12 As6 and Pd13 (PhAs)8 require additional toxicity analysis.",
publisher = "Zagreb, Croatia : Institute for Medical Research and Occupational Health",
journal = "Archives of Industrial Hygiene and Toxicology",
title = "Polyoxopalladates as potential antitumor drugs: in vitro toxicity assessment",
volume = "72",
number = "Suppl. 1",
pages = "65-65",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12963"
}
Čolović, M., Gajski, G., Ma, T., Isaković, A., Misirlić-Denčić, S., Kortz, U.,& Krstić, D.. (2021). Polyoxopalladates as potential antitumor drugs: in vitro toxicity assessment. in Archives of Industrial Hygiene and Toxicology
Zagreb, Croatia : Institute for Medical Research and Occupational Health., 72(Suppl. 1), 65-65.
https://hdl.handle.net/21.15107/rcub_vinar_12963
Čolović M, Gajski G, Ma T, Isaković A, Misirlić-Denčić S, Kortz U, Krstić D. Polyoxopalladates as potential antitumor drugs: in vitro toxicity assessment. in Archives of Industrial Hygiene and Toxicology. 2021;72(Suppl. 1):65-65.
https://hdl.handle.net/21.15107/rcub_vinar_12963 .
Čolović, Mirjana, Gajski, Goran, Ma, Tian, Isaković, Anđelka, Misirlić-Denčić, Sonja, Kortz, Urlich, Krstić, Danijela, "Polyoxopalladates as potential antitumor drugs: in vitro toxicity assessment" in Archives of Industrial Hygiene and Toxicology, 72, no. Suppl. 1 (2021):65-65,
https://hdl.handle.net/21.15107/rcub_vinar_12963 .

Cytogenotoxicity assessment of polyoxopalladates(II) as promising antileukemic drug candidates

Čolović, Mirjana; Gajski, Goran; Gerić, M.; Ma, T.; Ma, X.; Kortz, Ulrich; Krstić, Danijela

(Belgrade : Society of Physical Chemists of Serbia, 2021)

TY  - CONF
AU  - Čolović, Mirjana
AU  - Gajski, Goran
AU  - Gerić, M.
AU  - Ma, T.
AU  - Ma, X.
AU  - Kortz, Ulrich
AU  - Krstić, Danijela
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12923
AB  - Polyoxopalladates(II) (POPs) are discrete, anionic palladium(II)- oxo nanoclusters that possess features of both conventional polyoxometalates (POMs) and palladium(II), which were shown to exhibit promising antitumor properties. In this study, in vitro cyto- and genotoxicity evaluation was performed on normal non-target human blood cells using two isostructural POPs with tetravalent metal ions (SnIV, PbIV) encapsulated in the cuboid Pd12-oxo host, Na12[SnO8Pd12(PO4)8]·43H2O (SnPd12) and Na12[PbO8Pd12(PO4)8]·38H2O (PbPd12), with confirmed in vitro antileukemic actions against HL-60 cell line. For this purpose, whole blood samples were exposed to the POPs, at concentrations of ≈ IC50 (24 h) values, resulting in cytotoxicity in HL-60 cells for 24 h at 37 °C. The cytotoxicity studies were performed on human peripheral blood mononuclear cells which were stained with acridine orange and ethidium bromide, and then viewed under a fluorescence microscope. The genotoxicity was tested in whole blood by the alkaline comet assay (microgel electrophoresis). The results of the cytotoxicity evaluation and the comet assay demonstrated that none of the tested POPs, within the investigated concentration range 12.5 – 50 µM, resulted in a statistically significant modulation of blood cell viability as well as DNA damage, expressed as % of tail DNA (relative increase of tail DNA), compared to the untreated controls. Therefore, the promising antileukemic drug candidates, SnPd12 and PbPd12, can be considered as selective and safe from a cytogenotoxicity point of view.
PB  - Belgrade : Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2021 : 15th international conference on fundamental and applied aspects of physical chemistry : Proceedings
T1  - Cytogenotoxicity assessment of polyoxopalladates(II) as promising antileukemic drug candidates
VL  - 2
SP  - 414
EP  - 417
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12923
ER  - 
@conference{
author = "Čolović, Mirjana and Gajski, Goran and Gerić, M. and Ma, T. and Ma, X. and Kortz, Ulrich and Krstić, Danijela",
year = "2021",
abstract = "Polyoxopalladates(II) (POPs) are discrete, anionic palladium(II)- oxo nanoclusters that possess features of both conventional polyoxometalates (POMs) and palladium(II), which were shown to exhibit promising antitumor properties. In this study, in vitro cyto- and genotoxicity evaluation was performed on normal non-target human blood cells using two isostructural POPs with tetravalent metal ions (SnIV, PbIV) encapsulated in the cuboid Pd12-oxo host, Na12[SnO8Pd12(PO4)8]·43H2O (SnPd12) and Na12[PbO8Pd12(PO4)8]·38H2O (PbPd12), with confirmed in vitro antileukemic actions against HL-60 cell line. For this purpose, whole blood samples were exposed to the POPs, at concentrations of ≈ IC50 (24 h) values, resulting in cytotoxicity in HL-60 cells for 24 h at 37 °C. The cytotoxicity studies were performed on human peripheral blood mononuclear cells which were stained with acridine orange and ethidium bromide, and then viewed under a fluorescence microscope. The genotoxicity was tested in whole blood by the alkaline comet assay (microgel electrophoresis). The results of the cytotoxicity evaluation and the comet assay demonstrated that none of the tested POPs, within the investigated concentration range 12.5 – 50 µM, resulted in a statistically significant modulation of blood cell viability as well as DNA damage, expressed as % of tail DNA (relative increase of tail DNA), compared to the untreated controls. Therefore, the promising antileukemic drug candidates, SnPd12 and PbPd12, can be considered as selective and safe from a cytogenotoxicity point of view.",
publisher = "Belgrade : Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2021 : 15th international conference on fundamental and applied aspects of physical chemistry : Proceedings",
title = "Cytogenotoxicity assessment of polyoxopalladates(II) as promising antileukemic drug candidates",
volume = "2",
pages = "414-417",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12923"
}
Čolović, M., Gajski, G., Gerić, M., Ma, T., Ma, X., Kortz, U.,& Krstić, D.. (2021). Cytogenotoxicity assessment of polyoxopalladates(II) as promising antileukemic drug candidates. in PHYSICAL CHEMISTRY 2021 : 15th international conference on fundamental and applied aspects of physical chemistry : Proceedings
Belgrade : Society of Physical Chemists of Serbia., 2, 414-417.
https://hdl.handle.net/21.15107/rcub_vinar_12923
Čolović M, Gajski G, Gerić M, Ma T, Ma X, Kortz U, Krstić D. Cytogenotoxicity assessment of polyoxopalladates(II) as promising antileukemic drug candidates. in PHYSICAL CHEMISTRY 2021 : 15th international conference on fundamental and applied aspects of physical chemistry : Proceedings. 2021;2:414-417.
https://hdl.handle.net/21.15107/rcub_vinar_12923 .
Čolović, Mirjana, Gajski, Goran, Gerić, M., Ma, T., Ma, X., Kortz, Ulrich, Krstić, Danijela, "Cytogenotoxicity assessment of polyoxopalladates(II) as promising antileukemic drug candidates" in PHYSICAL CHEMISTRY 2021 : 15th international conference on fundamental and applied aspects of physical chemistry : Proceedings, 2 (2021):414-417,
https://hdl.handle.net/21.15107/rcub_vinar_12923 .