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Photochemistry of polycyclic molecules: From mechanistic studies to new drugs and medicinal applications

Principal investigator

Category
Projekti Hrvatske zaklade za znanost
Start date
Jul 1st 2010
End date
Sep 30th 2013
Status
Done

Photons are phenomenal reagents which open new opportunities in chemical synthesis that cannot be attained in the chemistry of ground state. The goal of the project was to find new photochemical transformations applicable in organic synthesis, as well as investigation of the photochemical reaction mechanisms. In addition, the aim of the project was to go beyond the state of the art, and ultimately find application of photochemistry in new medical treatments and synthesis of new compounds, potential drug molecules for treating malignant diseases.

The main instrument for achieving the goals of the project was research on new photochemical transformations and finding ways of understanding their reaction mechanisms, which took three main directions:

a) photochemistry of polycyclic phthalimides for the production of potential anticancer and antiviral agents;

b) photochemical formation of polycyclic quinone methides, new potential anticancer therapeutics;

c) understanding photochemical reaction mechanisms of H+ and H˙ transfer on the examples of photochemical transformations of aryl-pyrroles and aryl-indoles

A) Photochemistry of polycyclic phthalimides

Polycyclic cage molecules are important organic compounds because of their properties such as rigid structure, lipophilicity and biological activity. Adamantane is the most well-known cage molecule. It is very important pharmacophore, as well as the ideal model for studying chemical reactivity. Consequently, it is highly important to develop novel synthetic methods for the preparation of new functionalized adamantane derivatives.

In the course of the bilateral DAAD project with the group of Professor A.G. Griesbeck, new polycyclic adamantane derivatives were synthesized by employing photochemical methodology (Org. Lett., 2008 10, 3965-3968; J. Org. Chem., 2009, 74, 8219-8231). For that purpose adamantane derivatives were activated by a phthalimide group which is known as a very convenient chromophore that undergoes various photochemical reactions such as homolytic H-abstraction, [2+2] cycloaddition, photoreduction and electron-transfer (Croatica Chemica Acta, 2010, 83, 179-188). Photochemical reactions of adamantane-phthalimides give more complex polycyclic molecules, with an anticipated anticancer and antiviral activity. 

Within the framework of the HRZZ project, the phthalimide moiety was introduced to different positions of cage molecules such as homoadamantane and protoadamantne, and we carried out investigation of the photochemical reactivity. Upon excitation to the triplet excited state, an intramolecular H-abstraction from the cage skeleton takes place. The H-abstraction gives rise to biradicals that recombine giving complex polycyclic molecules with potential biological activity (Beilstein J. Org. Chem. 2011, 7, 270-276). Formation of inclusion complexes with β-cyclodextrines or irradiation in the solid state change photochemical reactivity and lead to different photo-products or different ratio of regioisomers (Eur. J. Org. Chem. 2013, 929-938)

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The antiproliferative activity was investigated on a small library of adamantyl derivatives of phthalimides. All the compounds are characterized by antiproliferative activity that is higher than the activity of commercial anticancer drug Thalidomide (Chem. Biol. Drug Des. 2012, 79, 497-506). In addition, the same library of compounds was tested for antiviral activity on Herpes simplex, HIV, CMV, and VZV viruses (manuscript in preparation). The testing was performed in the Rega institute in Leuven, Belgium.

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The research has also been extended to photochemistry of polycyclic derivatives of amino acids. The unnatural adamantane amino acid was activated by the phthalimide chromophore. Irradiation of 1,3-adamantane derivative leads to a photoinduced electron transfer followed by a decarboxylation. The decarboxylation gives rise to radical intermediates that were used in the addition reactions to olefins with electron-withdrawing groups. The mechanism of the photochemical reaction was elucidated by use of transient spectroscopy. The LFP enabled detection of the triplet excited state. In addition, regiospecific incorporation of deuterium in the molecule upon irradiations in deuterated solvents indicated presence of radical and carbanion intermediates (Photochem. Photobiol. Sci. 2011, 10, 610-617).

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Photoinduced decarboxylation was also investigated on a series of dipeptides that at the N-terminus bear N-adamantylphthalimide or N-phenylphthalimide, and at the C-terminus bear phenylalanine or glycine. The photodecarboxylation of N-adamantyl derivatives probably proceeds from both singlet and triplet excited state, whereas cyclization products probably arise from the triplet excited state. The photodecarboxylation of N-phenylphthalimide probably takes place from the triplet excited state, which was characterized by laser flash photolysis. N-phenylphthalimides undergo 2-5 times more efficient photodecarboxylation than N-adamantylphthalimides. The aminoacid residue (Phe or Gly) at the C-terminus of the dipeptide does not influence the photodecarboxylation efficiency. Product selectivity in the photoreactions is determined by the conformation of the molecules. N-phenylphthalimides with the separated electron donor (carboxylate) and acceptor moiety (phthalimide) give only simple decarboxylation products, whereas N-adamantyl derivatives give cyclization products (manuscript in peraparation).

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Photoinduced decarboxylation is currently investigated on a series of tetra- and pentapeptides that at the C-terminus bear different electron-donating substituent. It is anticipated that electron donating substituent should affect the photodecarboxylation and cyclization efficiency.

B) Photochemical generation of quinone methides

The major goal of this research direction is development of new class of quinone methides (QM) characterized by exceptionally long lifetimes, and therefore with potential applicability in biology and medicine. Although this research is multidisciplinary, involving organic synthesis, spectroscopy, theoretical chemistry and biology, a major part is concerned with the synthesis and the photochemistry. A special emphasis in this research topic is given to spectroscopic characterization of QMs that was performed in a collaboration with the group of Professor P. Wan, at the University of Victoria (Canada, BC), equipped with laser facilities necessary for the spectroscopic characterization of QMs (transient spectroscopy, laser flash photolysis LFP, single photon timing). Testing of the antiproliferative activity was performed in cooperation with the Laboratory for Experimental Therapy, at the Department for Molecular Medicine.

To date we have investigated photochemical reactivity of simple phenol derivatives and shown that incorporation of adamantane substituent at the methylene position of QM significantly increases lifetime of these transient species (J. Org. Chem., 2010, 75, 102-116).

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In continuation of the research, new phenylphenol derivatives were synthesized wherein extended conjugation enabled excitation by light of longer wavelengths (> 254 nm). The first series were adamantyl derivatives of 2-phenylphenol. We found out that excitation of the investigated compounds leads to two competitive excited state processes, intramolecular proton transfer from the phenolic OH (ESIPT) and protonation of the carbon atom of the adjacent phenyl substituent, as well as formal proton transfer and dehydration. Both processes lead to the formation of QMs. However, only QMs formed in dehydration reactions were sufficiently long-lived to be detected by nanosecond LFP. QMs formed by ESIPT are very short-lived and very rapidly tautomerize to the starting phenol molecules (Can. J. Chem. 2011, 89, 221-234).

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To prevent the ESIPT to carbon atom of an adjacent phenyl ring, we studied the next generation of the compounds, the derivatives of 4-phenylphenol and 3-phenylphenol. In aqueous media, photochemical excitation (S1) of hydroxyadamantyl, diphenylhydroxymethyl, and hydroxypropyl derivatives of 4-phenylphenol leads to solvent-assisted deprotonation of the phenol OH, and protonation of the benzyl alcohol coupled with dehydration that delivers QMs. The QMs react with CH3OH converting them in high quantum yields to the photosolvolysis products (overall F ~ 0.1-0.5). QMs were characterized by LFP in CH3CN-H2O and TFE. In TFE para QMs have lifetimes of 500 μs - 1.1 s. Introduction of the steric hindrance to the parent QM structure (with the adamantyl moiety), or additional stabilization by two phenyl rings, results in an increase of QM lifetimes and selectivity in the reactions with nucleophiles (Photochem. Photobiol. Sci. 2011, 10, 1910-1925).

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Photochemical excitation (S1) of 3-phenylphenol delivers QMs that have zwitterionic structure. The zwitterions react with nucleophiles (CH3OH, CF3CH2OH and ethanolamine) converting them in high quantum yields to the corresponding adducts and photosolvolysis products (for photomethanolysis F ~ 0.1-0.5). The diphenyl substituted zwitterions were characterized by LFP in CH3CN-H2O (τ~7.5 and 25μs) and the associated quenching rate constants with nucleophiles azide and ethanolamine determined.In vitro studies of antiproliferative activity of the photochemicaly generated QMs and zwitterions formed from 2-, 3- and 4-phenylphenols were carried out on three human cancer cell lines HCT 116 (colon), MCF-7 (breast), and H 460 (lung). Irradiation of cells incubated showed enhanced antiproliferative activity compared to the cells that were not irradiated in accordance with the activity being due to the formation of QMs (Photochem. Photobiol. Sci.2012,11, 381-396).

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Photochemical reactivity in the photodehydration reaction was also investigated in a series of 1- and 2-(2-hydroxy-2-adamantyl)naphthol derivatives. Excitation of 3-substituted-2-naphthol to S1 leads to efficient excited state intramolecular proton transfer (ESIPT) coupled with dehydration, giving quinone methide which was characterized by LFP (in CH3CN-H2O, λmax = 370 nm, τ =0.19 ms). On irradiation in CH3OH-H2O (4:1), the quantum yield of methanolysis is Φ = 0.70. Excitation of 6- and 7-substituted-2-naphthol to S1 in CH3CN leads to photoionization and formation of naphthoxyl radicals, whereas in a protic solvent they undergo solvent-assisted PT giving QMs that react with nucleophiles delivering adducts, but with a significantly lower quantum efficiency. 5-Substituted-1-naphthol in a protic solvent undergoes two competitive processes, photosolvolysis via QM and solvent-assisted PT to carbon atom of the naphthalene giving zwitterion. The QM has been characterized by LFP (in CH3CN-H2O, λmax > 600 nm, τ =0.9 ms). In addition to photogenerated QMs, two stable naphthalene QMs were synthesized thermally and characterized by X-ray crystallography. Antiproliferative activity was investigated on three human cancer cell lines. Exposure of MCF-7 cells treated with 3-substituted-2-naphthol to 300 nm irradiation leads to enhanced antiproliferative effect, in accordance with the activity being due to the formation of QM (J. Org. Chem. 2012, 77, 4596-4610).

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The chromophoric system in the substrates that are anticipated to undergo photodehydration was further extended by incorporating an additional phenyl ring between the phenol OH and the naphthalene. Six new naphthylphenols, bearing bulky hydroxymethyl substituents on the naphthalene, were synthesized and their photoreactivity investigated by preparative irradiations, fluorescence measurements, and LFP. All derivatives (in S1) undergo deprotonation of the phenolic OH in the aqueous solution. Formation of QMs most probably takes place sequentially, triggered by the phenol deprotonation. Photodehydration takes place only for adamantyl derivatives and 2,6-substituted naphthalenes delivering the corresponding QMs which react with nucleophilic solvents giving the corresponding photosolvolysis products. The other less likely option for the formation of the observed solvolysis products may involve some radical species. The most efficient photosolvolyses were observed for the 2,6-substituted naphthalenes (Photochem. Photobiol. Sci. 2013, in press).

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In some chromophoric systems photosolvolysis reaction takes plave with lower efficiency due to competing photochemical process, ESIPT from the phenolic OH to a carbon atom of the adjecent phenyl ring. Therefore, we investigated the ESIPT process in selected examples of naphthylphenols and phenylnaphthols. Thus, irradiation of 2-phenyl-1-naphthol in CH3CN-D2O (3:1) leads to very efficient incorporation of deuterium at the ortho positions of the adjacent phenyl ring (overall Ф = 0.73±0.07), along with minor incorporation at the naphthalene positions 5 and 8. These finding are explained by excited state intramolecular proton transfer (ESIPT) from the phenol OH to the corresponding carbon atoms, the main pathway giving rise to quinone methide, which has been characterized by LFP (τ ≈ 20 ns; 460 nm). The ESIPT reaction paths have been explored with the second order approximate coupled cluster (CC2) method. In non-protic solvents the ESIPT from the naphthol O-H to the ortho position of the phenyl ring proceeds in a barrierless manner along the 1La energy surface via a conical intersection with the S  state, delivering QM. In aqueous solvent, clusters with H2O are formed wherein proton transfer (PT) to solvent and a H2O-mediated relay mechanism gives rise to naphtholates and QMs. To date, this ESIPT represents the moste efficient protonation of carbon atom in the excited state (Chem. Eur. J. 2012, 18, 10617-10623)

ESPIT

ESIPT and solvent-assisted ESPT in isomeric phenyl naphthols and naphthyl phenols were also investigated by preparative photolyses in CH3CN-D2O, fluorescence spectroscopy, LFP, and ab initio calculations. ESIPT takes place only in 2-(2-hydroxyphenyl)naphthalene (D-exchange Φ = 0.3), whereas the other derivatives undergo solvent-assisted PT with much lower efficiencies. The efficiency of the ESIPT and solvent-assisted PT is mainly determined by different populations of the reactive conformers in the ground state and the NEER principle. The D-exchange experiments and calculations using RI-CC2/cc-pVDZ show that S1 deactivates by direct ESIPT from the OH to the naphthalene position 1 through a conical intersection with S , delivering QM that was detected by LFP (τ = 26 ± 3 ns). ESIPT to the position 3 is possible but it proceeds from a less-populated conformer and involves an energy barrier on S1. In solvent-assisted PT to the naphthalene position 4, zwitterion is formed that cyclizes to stable naphthofuran photoproducts. The regiochemistry of the deuteration in solvent-assisted PT was correlated with the NBO charges of the corresponding phenolates/naphtholates. Combined experimental and theoretical data indicate that solvent-assisted PT takes place via a sequential mechanism involving first deprotonation of the phenol/naphthol, followed by the protonation by H2O in the S1 state of phenolate/naphtholate. The site of protonation by H2O is mostly at the naphthalene α-position (J. Org. Chem. 2013, 78, 1811-1823).

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In addition to the above mentioned antiproliferative investigations of phenols and naphthols, several libraries of compounds were screened for antibacterial activity. The testing was performed at the Natal University, Durban, South Africa on Klebsiella pneumoniae, Escherichia coli, Candida albicans, Bacillus Subtilis, and Staphylococcus aureus (manuscript in preparation).

C) Photochemical reaction mechanisms of H+ and H˙ transfer

The main objective of this working package, is finding examples of pyrrole and indole molecules wherein the NH would becomes enough acidic in the singlet excited state to undergo ESPT and protonate carbon atom. Furthermore, the important task of this working package is investigation of mechanisms of the (formal) intramolecular H transfer.

To date, we have investigated a possibility of a transfer of a proton on series of phenylpyrroles and phenylindoles. We found out that NH in the singlet excited state is not enough acidic to undergo the intramolecular proton transfer and protonate the carbon atoms. However, upon irradiation in deuterated solvents, deuterium incorporation takes place. The mechanism of the deuterium incorporation involves photoionization and formation of radical-cations. Quantum yield of deuterium incorporation can be correlated with the oxidation potentials of the compounds (Photochem. Photobiol. Sci.2011,10, 610-617).

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Further, we have synthesized three new cyanophenylpyrrole derivatives. It was anticipated that introduction of the CN group would increase polarization of the molecule in S1, and possibly set the stage for ESIPT or solvent-assisted ESPT to carbon atoms of the cyanophenyl ring. However, we found that molecules exhibit very high quantum yields of fluorescence, ΦF (0.2-0.9) and S1 lifetimes in the rage 2-8 ns. In addition, cyanophenylpyrroles exhibit strong solvatochrmoic properties suggesting high ICT character of the excited state. Increase of the solvent polarity does not quench fluorescence, but increases fluorescent lifetimes. The absorption spectra were calculated at B3LYP/6-31 level of theory indicating similar energy of S1 and S2, probably resulting in the state mixing and CT character of the relaxed S1 states. Ultrafast absorption measurements were performed in collaboration with the group of Prof. Elisei at the University of Perugia, Italy (manuscript in preparation). The measurements indicated existence of three transient species assigned to torsional motion of the C-C bond between the phenyl and the pyrrole ring (several picoseconds), solvent reorganization after reaching the relaxed S1 state (several hundreds of picoseconds), and radiactive decay of the relaxed S1 state (nanoseconds).

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graf_smal

Solvent-assisted ESIPT to distal sites has also been investigated in a series of four new terphenyl analogues of pyrrolylpyridines. The photophysical properties of the molecules were investigated by fluorescence spectroscopy, whereas formation of the photo-tautomers was probed by LFP. In addition, we invstigated the ability of pyridinium hydrochloride derivative to form inclusion complexes with cucurbiturils CB[6], CB[7], and CB[8] and undergo the same photo-tautomerization in the cavity of the inclusion complex. The research is performed in collaboration with a group of Prof. Bohne at the University of Victoria, Canada, BC (manuscript in preparation).

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Co-workers:

  • Dr. Nikola Basarić, senior scientist (project leader)
  • Prof. Dr. Kata Majerski, senior scientist
  • Dr. Jelena Veljković, research associate
  • Dr. Margareta Horvat, researcher
  • Dipl. ing. Jakov Ivković (researcher, April 1-August 16, 2011.)
  • Mag. chem. Đani Škalamera (researcher, August 29, 2011-March 30, 2012.; PhD student April 1, 2012 – to date)
  • Mag. appl. chem. Martina Tireli (researcher, May 2, 2012-September 30, 2012.)
  • Mag. appl. chem. Leo Mandić (researcher October 1, 2012.-June 30, 2013.; PhD student July 1, 2013 – to date)
  • Dr. Marijeta Kralj, senior scientist (Laboratory for experimental therapy, Department for molecular medicine)
  • Dr. Nađa Došlić, senior research associate (Group for theoretical chemistry, Department for physical chemistry)

Students and volunteers:

  • B.Sc.Nikola Cindro (volunteer from 2008, student of chemistry at the Faculty of Science, University of Zagreb)
  • Dipl. ing. Damir Bobinac (volunteer from 2010, PhD Student at the Faculty of Chemical Engineering and Technology, University of Zagreb)
  • Mag. chem. Lucija Ptiček (student, January-July, 2011., Diploma thesis: Synthesis of hydroxy-derivatives of naphthalene and anthracene, precursors in the photochemical synthesis of quinone methides, Faculty of Science, University of Zagreb, July 12, 2011)
  • B.Sc. Nikolina Vidović (volunteer from 2011, student of chemistry at the Faculty of Science, University of Zagreb)
  • Mag. chem. Matija Sambol (student, September-to date, Diploma thesis: Synthesis of benzene, naphthalene and anthracene precursors of bis(qinomethane), Faculty of Science, University of Zagreb, July 4, 2013).

Published papers:

14. N. Basarić, K. Mlinarić-Majerski, M. Kralj: “Quinone methides: photochemical generation and its application in biomedicine”,Curr. Org. Chem. (2013) in press.

13. Đ. Škalamera, K. Mlinarić-Majerski, L. Uzelac, M. Kralj, P. Wan, N. Basarić: “Photosolvolysis of bulky (4-hydroxyphenyl)naphthalene derivatives”,Photochem. Photobiol. Sci.(2013) in press.

12. J. Veljković, I. Antol, N. Basarić, V. Smrečki, K. Molčanov, N. Müller, K. Mlinarić-Majerski: “Atropisomerism in 1-(2-adamantyl)naphthalene derivatives”,J. Mol. Struct. 1046 (2013) 101-109.

11. N. Cindro, I. Halasz, K. Mlinarić-Majerski, N. Basarić: “Photoinduced H-abstraction in homo- and protoadamantylphthalimide derivatives in solution and in organized and constrained media”,Eur. J. Org. Chem. (2013) 929-938.

10. N. Basarić, N. Došlić, J. Ivković, Y.-H. Wang, J. Veljković, K. Mlinarić-Majerski, P. Wan: “Excited State Intramolecular Proton Transfer (ESIPT) from Phenol to Carbon in Selected Phenylnaphthols and Naphthylphenols”,J. Org. Chem. 78 (2013) 1811-1823.

9. N. Basarić, N. Došlić, J. Ivković, Y.-H. Wang, M. Mališ, P. Wan: “Very Efficient Generation of Quinone Methides via Excited State Intramolecular Proton Transfer (ESIPT) to Carbon Atom”,Chem. Eur. J.18 (2012) 10618-10623.

8. J. Veljković, L. Uzelac, K. Molčanov, K. Mlinarić-Majerski, M. Kralj, P. Wan, N. Basarić: “Sterically Congested Adamantylnaphthalene Quinone Methides”,J. Org. Chem. 77 (2012) 4596-4610.

7. N. Basarić, N. Cindro, D. Bobinac, L. Uzelac, K. Mlinarić-Majerski, M. Kralj, P. Wan: “Zwitterionic biphenyl quinone methides in photodehydration reactions of 3-hydroxybiphenyl derivatives: laser flash photolysis and antiproliferation study”Photochem. Photobiol. Sci. 11 (2012) 381-396.

6. M. Horvat, L. Uzelac, M. Marjanović, N. Cindro, O. Franković, K. Mlinarić-Majerski, M. Kralj, N. Basarić: “Evaluation of antiproliferative effect of N-(alkyladamantyl)phthalimides in vitro”,Chem. Biol. Drug Des. 79 (2012) 497-506.

5. N. Basarić, N. Cindro, D. Bobinac, K. Mlinarić-Majerski, L. Uzelac, M. Kralj, P. Wan: “Sterically congested quinone methides in photodehydration reactions of 4-hydroxybiphenyl derivatives and investigation of their antiproliferative activity”,Photochem. Photobiol. Sci. 10 (2011) 1910-1925.

4. M. Horvat, K. Mlinarić-Majerski, A.G. Griesbeck, N. Basarić: “Photoinduced decarboxylation of 3-(N-phthalimido)adamantane-1-carboxylic acid and radical addition to electron deficient alkenes”,Photochem. Photobiol. Sci.10 (2011) 610-617.

3. N. Cindro, M. Horvat, K. Mlinarić-Majerski, A.G. Griesbeck, N. Basarić: “Photoinduced homolytic C-H activation inN-(4-homoadamantyl)phthalimide”,Beilstein J. Org. Chem.7 (2011) 270-276.

2. N. Basarić, N. Cindro, Y. Hou, I. Žabčić, K. Mlinarić-Majerski, P. Wan: “Competing photodehydration and ESIPT in adamantyl derivatives of 2-phenylphenols”,Can. J. Chem.89 (2011) 221-234.

1. N. Basarić, A. Franco-Cea, M. Alešković, K. Mlinarić-Majerski, P. Wan: “Photochemical deuterium exchange in phenyl substituted pyrroles and indoles in CD3CN-D2O”,Photochem. Photobiol. Sci.9 (2010) 779-790.

 

Conference presentations:

14. N. Basarić, Đ. Škalamera, K. Mlinarić-Majerski, P. Wan: “Quinone methides in the photodehydration of 2-hydroxy-3-(hydroxymethyl)anthracenes”,XXVI International Conference on Photochemistry ICP 2013, Leuven, Belgium, 2013 (lecture).

13. N. Basarić: “Quinone methides: photochemical generation and antiproliferative activity”  XXIII. Croatian meeting of chemists and chemical engineers, Osijek, 2013 (lecture).

12. N. Cindro, N. Basarić, K. Mlinarić-Majerski, P. Wan: “Photochemical formation and reactivity of homoadamantyl - and protoadamantyl-zwitterions”,XXIII. Croatian meeting of chemists and chemical engineers, Osijek, 2013 (poster).

11. M. Sohora, T. Šumanovac Ramljak, K. Mlinarić-Majerski, N. Basarić: “Synthesis and photochemistry of novel N-phthalimido dipeptides”XXIII. Croatian meeting of chemists and chemical engineers, Osijek, 2013 (poster).

10. Đ. Škalamera, M. Sambol, J. Veljković, K. Mlinarić-Majerski, N. Basarić: “Optimized synthetic pathway to anthrol carbaldehydes” / XXIII. Croatian meeting of chemists and chemical engineers, Osijek, 2013 (poster).

9. Đ. Škalamera, N. Basarić, K. Mlinarić-Majerski, P. Wan: “Excited state intramolecular proton transfer (ESIPT) in 3-hydroxyanthracene-2-carbaldehyde”e-WISPOC 2013 / 2nd Training School COST Action CM1005 Supremolecular Chemistry in Water, Bressanone, Italy, 2013 (poster).

8. N. Basarić: “Photochemical formation of quinone methides and investigation of their antiproliferative effect”,4th Young Investigators Workshop, Wiena, Austria, 2012 (lecture).

7. Đ. Škalamera, K. Mlinarić-Majerski, N. Basarić, P. Wan: “Photodehydration in 4-[(hydroxymethyl)naphthyl]phenol derivatives “,Photochemistry 2012: Fundamentals and Applications, Wijk aan Zee, Netherland, 2012 (poster).

6. N. Basarić, N. Došlić, J. Ivković, Y.-H. Wang, J. Veljković, M. Mališ, K. Mlinarić-Majerski, P. Wan: “Very Efficient New Examples of Excited State Intramolecular Proton Transfer (ESIPT) to Carbon”XXIV IUPAC Symposium on photochemistry, Coimbra, Portugal, 2012 (poster).

5. N. Basarić, J. Veljković, K. Mlinarić-Majerski, L. Uzelac, M. Kralj, P. Wan: “Photochemical formation and investigation of antiproliferative effect of adamantylnaphthalene quinone methides”,Central European Conference on Photochemistry CECP 2012, Bad Hofgastein, Austria, 2012 (poster).

4. N. Cindro, K. Mlinarić-Majerski, I. Halasz, A. Griesbeck,  N. Basarić: “Mechanistic study of photoinduced intramolecular H-abstraction in endo- and exo- protoadamantylphthalimides”Central European Conference on Photochemistry CECP 2012, Bad Hofgastein, Austria, 2012 (poster).

3. N. Basarić, D. Bobinac, N. Cindro, K. Mlinarić-Majerski, L. Uzelac, M. Kralj, P. Wan: “Characterization of sterically congested biphenyl quinone methides and zwitterions by laser flash photolysis, and investigation of their antiproliferative activity”,XXV International Conference on Photochemistry ICP 2011, Bejing, China, 2011 (lecture).

2. N. Cindro, M. Horvat, K. Mlinarić-Majerski, A. G. Griesbeck, N. Basarić: “Photoinduced H-abstraction inN-(4-homoadamantyl)phthalimide”XXII. Croatian meeting of chemists and chemical engineers, Zagreb, 2011 (poster).

1. N. Basarić, N. Cindro, D. Bobinac, I. Žabčić, K. Mlinarić-Majerski, Y. Hou, P. Wan: “Photochemistry of adamantyl derivatives of hydroxybiphenyls: ESIPT vs. photosolvolysis“2010 International Chemical Congress of Pacfic Basin Societies (lecture).

 

Public lectures:

1. N. Basarić: “Photochemical formation of quinone methides: investigation of reaction mechanism and antiproliferative activity”, June 20, 2012, RBI, Zagreb.

2. N. Basarić: “Formation of sterically congested quinone methides in photodehydration of phenols”, August 4, 2011, Lanzhou, China.

3. N. Basarić: “Photochemistry of polycyclic molecules: From mechanistic studies to new drugs and medicinal applications“, June 6, 2011, RBI, Zagreb.

4. N. Basarić: “Photochemistry of polycyclic molecules: From mechanistic studies to new drugs and medicinal applications“, August 26, 2010, RBI, Zagreb.

 

PhD Thesis

M. Horvat: “Synthesis and photochemistry of novel adamantyl phthalimide derivatives”, Faculty of Science, University of Zagreb, Septemer 15, 2011, Mentor: N. Basarić.

 

Diploma Thesis

M. Sambol: “Synthesis of benzene, naphthalene and anthracene precursors of bis(qinomethane)“, Faculty of Science, University of Zagreb, July 4, 2013, Mentor: N. Basarić.

L. Ptiček: “Synthesis of hydroxy-derivatives of naphthalene and anthracene, precursors in the photochemical synthesis of quinone methides, Faculty of Science, University of Zagreb, July 12, 2011, Mentor: N. Basarić.

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