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The planarity and the appropriate size of the porphyrin ring make porphyrin derivatives ideal ligands for stacking to guanine quartets and they could thus be used as anti-cancer drugs. In this contribution we analyzed complexes of a guanine quartet with a porphyrin molecule, magnesium porphyrin and calcium porphyrin. As magnesium and calcium ions are located in the center and above the porphyrin ring, respectively, the two metalloporphyrins are expected to have different impacts on the target. The optimized structures of the three systems revealed geometrical changes in the guanine quartet upon complexation: while stacking of porphyrin and magnesium porphyrin does not induce significant changes, calcium porphyrin considerably distorts the quartet's structure, which has significant implications for the binding properties among guanine molecules. Ab initio molecular dynamics simulations revealed that the systems perform small fluctuations around the equilibrium structures. The largest atom displacements are performed by the calcium ion. The interacting quantum atoms methodology enabled analysis of the binding properties in the studied complexes. Interestingly, although the proximity of the calcium ion is responsible for the quartet's pronounced deformation and weakening of guanine-guanine binding, it also enables stronger binding of the metal ion to the quartet, resulting in a more stable complex. These results imply that metalloporphyrin-like ligands with out-of-plane central ions might represent promising drug candidates in anti-tumor treatment.

Larger Coulombic repulsion between divalent cations compared to the monovalent counterparts dictates the cation-cation distance in the central ion channel of quadruplexes. In this work, density functional theory and a continuum solvation model were employed to study bond energies of alkaline earth cations in adjacent cavities of the central ion channel. Four crystallized tetramolecular quadruplexes with various geometric constraints and structural motifs available in the Protein Data Bank were examined in order to understand how the cation binding affinities could be increased in aqueous solution. A cytosine quartet sandwiched between guanine quartets has a larger bond energy of the second alkaline earth cation in comparison with guanine and uracil quartets. Four highly conserved hydrogen-bonded water molecules in the center of the cytosine quartet are responsible for a higher electrostatic interaction with the cations in comparison with guanines' carbonyl groups. The reported findings are valuable for the design of synthetic quadruplexes templated with divalent cations for optoelectronic applications.

Guanine self-assemblies are promising supramolecularplatforms for optoelectronic applications. The study (Hua et al., J. Phys. Chem. C 2012, 116, 14,682−14,689) reported that alkaline cations cannot modulate the electronic absorption spectrum of G-quadruplexes, although a cation effect is observableduring electronic relaxation due to different mobility of Na+ and K+ cations. In this work, we theoretically examined whether divalent Mg2+ and Ca2+ cations and hydration might shift excited charge-transfer states of a cation-templated stacked G-quartet to the absorption red tail. Our results showed that earth alkaline cationsblue-shifted nπ* states and stabilized charge-transfer ππ* states relative to those of complexes with alkaline cations, although the number of charge-separation states was not significantly modified. Earth alkaline cations were not able to considerably increase theamount of charge-transfer states below the Lb excitonic states. Hydration shifted charge-transfer states of the Na+-coordinated Goctet to the absorption red tail, although this part of the spectrum was still dominated by monomer-like excitations. We found Goctet electron detachment states at low excitation energies in aqueous solution. These states were distributed over a broad range of excitation energies and could be responsible for oxidative damage observed upon UV irradiation of biological G-quadruplexes.

Avobenzon (4-terc-butil-4’metoksidibenzoilmetan) je jedan od najpoznatijih najˇsire koriˇs´cenih filtera za zaˇstitu od UVA zraˇcenja. Avobenzon spada u grupu β-dikarbonilnih jedinjenja i ˇcija fotohemija ukljuˇcuje keto-enol tautomerizaciju, cis-trans izomerizaciju, rotaciju oko jednostruke veze kao i raskidanje karbonilnih grupa. Kako bi istraˇzili fotohemiju avobenzona izuˇcavani su tautomeri avobenzona: helatni i ne-helatni enol, rotamer Z, rotamer E kao i keto oblik u osnovnom i pobudenim stanjima u gasnoj fazi i acetonitrilu pomo´cu DFT i metode spregnutih klastera. Istraˇzivanje je pokazalo da torzija oko dvostruke C2-C3 veze fotopobudenog enolnog oblika vodi do unutraˇsnje konverzije u osnovno elektronsko stanje i formiranje rotamera E. Takode, otvaranje helatnog prstena i raskidanje vodoniˇcne veze rotacijom hidroksilne grupe uzrokuje stvaranje ne-helatnog enolnog oblika. Izuˇcavani su i mogu´ci mehanizmi za formiranje rotamera Z. Studija je pokazala da je zavisnost fotostabilnosti avobenzona od rastvaraˇca u direktnoj vezi sa relativnim rasporedom najniˇzeg tripletnog ππ∗ i nπ∗ stanja. Opis apsorpcionih osobina samo na osnovu vertikalnog ekscitacionog spektra raˇcunatog u minimumu povrˇsi potencijalne energije osnovnog elektronskog stanja, dovodi do zakljuˇcka da ne dolazi do inicijalnog pobudivanja nπ∗ stanja. S obzirom da pod uticajem termalnih i kvantnih efekata dolazi do znaˇcajnih promena u strukturi molekula avobenzona, za potpunije opisivanje sistema neophodno je uraˇcunati ne samo jednu konfiguraciju ve´c ansambl konfiguracija molekula. Tako je u ovom radu izvrˇsena simulacija spektara primenom DFT/MRCI metode zajedno sa ansamblom konfiguracija dobijenih pomo´cu metoda molekulske dinamike. Takode, izraˇcunati su i Frank-Kondonovi faktori za prelazak na ππ∗ stanje. Istraˇzivanje je pokazalo da termalne i kvantne fluktuacije simetriˇcno ˇsire apsorpcioni spektar u okviru poluklasiˇcne aproksimacije zbog ˇcega je neophodno uraˇcunati i vibronske efekt, Avobenzone (4-tert-butyl-4’-methoxydibenzoylmethane, AB) is one of the most popular and widely used organic filter for skin photoprotection in the UVA band. AB belongs to the class of a β-dicarbonyl compounds which undergoes keto-enol tautomerization, rotation around single bond, bond breaking of carbonyl groups and cis-trans isomerization. All of these structural changes of AB lead to formation of different forms of AB which we labeled as: rotamer E, rotamer Z, chelated enol, non-chelated enol and keto tautomer. In order to study the photochemistry of AB we examined AB tautomers in the ground and excited states in the gas phase and acetonitrile using the coupled cluster and DFT computational methods. Based on the results of this study, it can be concluded that the internal conversion to the ground state of photoexcited chelated enol and creation of rotamer E is a consequence of the rotation around C2-C3 double bond of the chelated enol form. In addition, non-chelated enol tautomer is formed as a result of torsion of the hydroxyl group and breaking of the hydrogen bond of the chelated ring. The possible mechanisms of rotamer Z creation are discussed. Examination of the keto tautomer triplet states revealed that the lowest triplet ππ∗ and nπ∗ states exchange their relative order depending on the solvent. Results acquired from the calculation of the vertical excitation spectrum at the minimum of the ground state potential energy surface indicate that nπ∗ state does not exhibit initial photoexcitation. Because thermal and quantum fluctuations cause major structural changes of AB molecule and in order to create overall picture of photoexcitation, it is necessary to consider an ensemble of configurations instead of one molecular configuration. In order to do so, we sampled different configurations using DFT-based classical and path integral molecular dynamics, which are later used to calculate UVA response at DFT/MRCI level of theory. Also, Franck-Condon factors are calc

Avarol je sekundarni metabolit izolovan iz morskog sunđera Dysidea avara. Smatra se da hidrohinonski segment molekula avarola ima ključnu ulogu u njegovoj biološkoj aktivnosti, dok je uloga terpenoidnog dela manje značajna. Avarol ima nisku toksičnost i širok dijapazon bioloških aktivnosti, između ostalog antioksidativnu, antiinflamatornu, antitumorsku, antipsorijatičnu i anti-HIV. Imajući u vidu ove činjenice, kao i to da avarol može proći kroz krvno-moždanu barijeru, on predstavlja dobrog kandidata za razvoj novih terapija za neurodegenerativne bolesti, posebno Alchajmerovu bolest. Međutim, problem primene avarola u terapijske svrhe ogleda se u njegovoj nerastvorljivosti u vodi. Pošto se smatra da su jedan od uzročnika Alchajmerove bolesti slobodni radikali, potrebno je detaljno ispitati prirodu interakcija avarola sa njima. U ovoj doktorskoj disertaciji, interakcije avarola sa slobodnim radikalima proučavane su primenom metoda teorijske hemije i elektronske paramagnetne rezonantne (EPR) spektroskopije. Zbog kompleksnosti sistema, kod teorijskih proračuna upotrebljen je hidrohinon kao model molekul. Osim toga, primenom ciklične voltametrije i ultraljubičaste i vidljive spektroskopije ispitana je interakcija avarola sa L-dopom, prekursorom kateholaminskih neurotransmitera. Teorijskim proračunima zasnovanim na teoriji funkcionala gustine (DFT), odnosno kvantnoj teoriji atoma u molekulima (QTAIM), ispitano je do kakvih interakcija dolazi između hidrohinona i tri radikala: hidroksilnog, hidroperoksilnog i metoksi radikala. Na osnovu rezultata teorijskih proračuna, ustanovljeno je da je energijska barijera za reakciju hidrohinona sa hidroperoksilnim radikalom znatno viša od barijere za reakciju hidrohinona sa hidroksilnim radikalom. Sem toga, reakcija apstrakcije vodonikovog atoma sa hidroksilne grupe hidrohinona od strane sva tri posmatrana radikala odvija se mehanizmom poznatim kao PCET (spregnuti prenos protona i elektrona, od eng. proton-coupled electron transfer)., avara. The hydroquinone moiety of avarol is supposed to play a key role in its biological activity, while the role of its terpenoid moiety is merely marginal. Avarol is known for its low toxicity and a wide range of biological activities, antioxidative, antiinflamatoric, antitumour, antipsoriatic and anti-HIV being some of the most important ones. Having this in mind, as well as the fact that avarol can cross through the blood-brain barrier, it could serve as a good candidate for the development of the new therapies for neurodegenerative diseases, principally Alzheimer’s disease. However, its poor solubility in water hampers its application in therapeutical purposes. Since free radicals are presumed to be one of the causes of Alzheimer’s disease, the nature of interactions of avarol with these species should be explored more elaborately. In this doctoral dissertation, interactios of avarol with free radicals have been studied by the means of computational chemistry and electron paramagnetic resonance (EPR) spectroscopy. Due to the complexity of the systems, hydroquinone was used as a model molecule for computational studies. The interaction of avarol with L-dopa (precursor for catecholamine neurotransmitters) was studied using cyclic voltammetry and ultraviolet-visible spectroscopy. Theoretical computations based on density functional theory (DFT), and quantum theory of atoms in molecules (QTAIM) were employed in order to study interactions between hydroquinone and three radical species: hydroxyl, hydroperoxyl and metoxy radicals. Based on the results of theoretical computations, it was found that the energy barrier for the reaction of hydroquinone with hydroperoxyl radical is significantly higher compared to its reaction with hydroxyl radical. The reaction of hydrogen atom abstraction from the hydroxyl group of hydroquinone by all three radicals follows PCET (proton coupled electron transfer) mechanism. By using the implicite solvent method, it was determined that

The dynamic aspect of solvation plays a crucial role in determining properties of strong intramolecular hydrogen bonds since solvent fluctuations modify instantaneous hydrogen‐bonded proton transfer barriers. Previous studies pointed out that solvent‐solute interactions in the first solvation shell govern the position of the proton but the ability of the electric field due to other solvent molecules to localize the proton remains an important issue. In this work, we examine the structure of the O−H⋅⋅⋅O intramolecular hydrogen bond of dibenzoylmethane in methanol solution by employing density functional theory‐based molecular dynamics and quantum chemical calculations. Our computations showed that homogeneous electric fields with intensities corresponding to those found in polar solvents are able to considerably alter the proton transfer barrier height in the gas phase. In methanol solution, the proton position is correlated with the difference in electrostatic potentials on the oxygen atoms of dibenzoylmethane even when dibenzoylmethane‐methanol hydrogen bonding is lacking. On a timescale of our simulation, the hydrogen bonding and solvent electrostatics tend to localize the proton on different oxygen atoms. These findings provide an insight into the importance of the solvent electric field on the structure of a strong intramolecular hydrogen bond

Паралелне стекинг интеракције η-координованих ароматичних лиганада и хелатних прстенова испитиване су претраживањем Кембричке базе структурних података и квантнохемијским прорачунима. Најјаче стекинг интеракције између координованих молекула бензена (-4,0 kcal/mol) и координованих циклопентадиенил-анјона (-3,3 kcal/mol) су паралелно-смакнуте, и јаче су од стекинг интеракција у димеру бензена (-2,7 kcal/mol). Међутим, анализа кристалних структура показала је да координовани бензен и циклопентадиенил-анјон формирају велики број стекинг интеракција на великим хоризонталним померањима, услед тога што формирање таквих интеракција доводи до успостављања стабилнијих супрамолекулских структура. Стекинг интеракције на великим хоризонталним померањима су веома типичне за сендвич-једињења бензена и циклопентадиенил-анјона, с обзиром да поседују око 75% енергије најјаче стекинг интеракције. Ове интеракције се ређе јављају између полусендвич-једињења, јер њихова јачина не прелази 55% енергије најјаче стекинг интеракције. За разлику од координованих ароматичних прстенова, хелатни прстенови не граде јаке стекинг интеракције на великим хоризонталним померањима. Најјаче хелат-арил стекинг интеракције имају паралелно-смакнуте геометрије, што је у сагласности са врло израженом доминацијом ових геометрија у кристалним структурама. Најјача израчуната стекинг интеракција између хелатног прстена acac типа и бензена има енергију од -7,2 kcal/mol, што хелат-арил интеракције чини значајно јачим од стекинг интеракција у димеру бензена. Утврђено је да јачине хелат-арил стекинг интеракција расту у 3d низу метала, услед јачања електростатичког привлачења, с обзиром на сличнедисперзионе интеракције. Јачине хелат-арил стекинг интеракција сличне су за све метале у 10. групи ПСЕ, као последица надокнађивања мање повољне електростатике повољнијом дисперзијом и обратно..., Parallel stacking interactions of η-coordinating aromatic ligands and chelate rings were studied by searching the Cambridge Structural Database and by performing quantum chemical calculations. The strongest stacking interactions between coordinating benzenes (-4.0 kcal/mol) and between coordinating cyclopentadienyl-anions (-3.3 kcal/mol) are parallel-displaced, and they are stronger than stacking interactions in benzene dimer (-2.7 kcal/mol). However, analysis of crystal structures has shown that coordinating benzene and cyclopentadienyl-anion form a large number of stacking interactions at large horizontal displacements, since the formation of these interactions leads to establishing of more stable supramolecular structures. Stacking interactions at large horizontal displacements are typical for sandwich compounds of benzene and cyclopentadienyl-anion, since they possess around 75% of energy of the most stable stacking interaction. These interactions occur less frequently between half-sandwich compounds, since their strength does not exceed 55% of energy of the strongest stacking interaction. Unlike coordinating aromatic rings, chelate rings do not form strong stacking interactions at large horizontal displacements. The strongest chelate-aryl stacking interactions have parallel-displaced geometries, which is in agreement with huge dominance of these geometries in crystal structures. The strongest calculated stacking interaction between acac type chelate ring and benzene has the energy of -7.2 kcal/mol, which makes chelate-aryl interactions much stronger than stacking interactions in benzene dimer. It was determined that the strength of chelate-aryl stacking interactions increases across the 3d row, due to increase in electrostatic attraction, with dispersion interactions being very similar. The strengths of chelate-aryl stacking interactions are similarfor all metals of Group 10, since less favorable electrostatics are compensated by more favorable dispersion, and

Паралелне стекинг интеракције η-координованих ароматичних лиганада и хелатних прстенова испитиване су претраживањем Кембричке базе структурних података и квантнохемијским прорачунима. Најјаче стекинг интеракције између координованих молекула бензена (-4,0 kcal/mol) и координованих циклопентадиенил-анјона (-3,3 kcal/mol) су паралелно-смакнуте, и јаче су од стекинг интеракција у димеру бензена (-2,7 kcal/mol). Међутим, анализа кристалних структура показала је да координовани бензен и циклопентадиенил-анјон формирају велики број стекинг интеракција на великим хоризонталним померањима, услед тога што формирање таквих интеракција доводи до успостављања стабилнијих супрамолекулских структура. Стекинг интеракције на великим хоризонталним померањима су веома типичне за сендвич-једињења бензена и циклопентадиенил-анјона, с обзиром да поседују око 75% енергије најјаче стекинг интеракције. Ове интеракције се ређе јављају између полусендвич-једињења, јер њихова јачина не прелази 55% енергије најјаче стекинг интеракције. За разлику од координованих ароматичних прстенова, хелатни прстенови не граде јаке стекинг интеракције на великим хоризонталним померањима. Најјаче хелат-арил стекинг интеракције имају паралелно-смакнуте геометрије, што је у сагласности са врло израженом доминацијом ових геометрија у кристалним структурама. Најјача израчуната стекинг интеракција између хелатног прстена acac типа и бензена има енергију од -7,2 kcal/mol, што хелат-арил интеракције чини значајно јачим од стекинг интеракција у димеру бензена. Утврђено је да јачине хелат-арил стекинг интеракција расту у 3d низу метала, услед јачања електростатичког привлачења, с обзиром на сличне дисперзионе интеракције. Јачине хелат-арил стекинг интеракција сличне су за све метале у 10. групи ПСЕ, као последица надокнађивања мање повољне електростатике повољнијом дисперзијом и обратно..., Parallel stacking interactions of η-coordinating aromatic ligands and chelate rings were studied by searching the Cambridge Structural Database and by performing quantum chemical calculations. The strongest stacking interactions between coordinating benzenes (-4.0 kcal/mol) and between coordinating cyclopentadienyl-anions (-3.3 kcal/mol) are parallel-displaced, and they are stronger than stacking interactions in benzene dimer (-2.7 kcal/mol). However, analysis of crystal structures has shown that coordinating benzene and cyclopentadienyl-anion form a large number of stacking interactions at large horizontal displacements, since the formation of these interactions leads to establishing of more stable supramolecular structures. Stacking interactions at large horizontal displacements are typical for sandwich compounds of benzene and cyclopentadienyl-anion, since they possess around 75% of energy of the most stable stacking interaction. These interactions occur less frequently between half-sandwich compounds, since their strength does not exceed 55% of energy of the strongest stacking interaction. Unlike coordinating aromatic rings, chelate rings do not form strong stacking interactions at large horizontal displacements. The strongest chelate-aryl stacking interactions have parallel-displaced geometries, which is in agreement with huge dominance of these geometries in crystal structures. The strongest calculated stacking interaction between acac type chelate ring and benzene has the energy of -7.2 kcal/mol, which makes chelate-aryl interactions much stronger than stacking interactions in benzene dimer. It was determined that the strength of chelate-aryl stacking interactions increases across the 3d row, due to increase in electrostatic attraction, with dispersion interactions being very similar. The strengths of chelate-aryl stacking interactions are similar for all metals of Group 10, since less favorable electrostatics are compensated by more favorable dispersion, and