Misonidatsolin ja 1-(2,3-epoksipropyyli)-2-nitroimidatsolin fragmentaatio fotoionisaation vaikutuksesta

Syövän sädehoidossa syöpäsolujen DNA:han pyritään aiheuttamaan pysyviä vaurioita ionisoivalla säteilyllä, minkä seurauksena solut kuolevat. Koska säteily vaurioittaa myös kasvainta ympäröiviä terveitä soluja, on tärkeää saavuttaa hoidon tavoitteet mahdollisimman pienellä säteilyannoksella. Syöpäkudos on usein niukkahappista solujen hallitsemattoman kasvun johdosta, mikä tekee kudoksesta resistentimmän säteilylle kuin normaalisti hapettuneen kudoksen. Yksi ratkaisu tähän ongelmaan on sädeherkistävien lääkemolekyylien käyttö. Tässä tutkielmassa tarkasteltiin misonidatsolin ja 1-(2,3-epoksipropyyli)-2-nitroimidatsolin fragmentaatiota valenssikuoren fotoionisaation jälkeen. Molekyyleistä misonidatsoli on tunnettu sädeherkiste. 1-(2,3-epoksipropyyli)-2-nitroimidatsolilla ei tiedetä olevan sädeherkistäviä ominaisuuksia mutta sillä on misonidatsolin tavoin 2-nitroimidatsoli-rakenne. Tutkielman tarkoituksena on vertailla miten eri funktionaaliset ryhmät molekyylien hajoamiseen. Työn kokeellinen osuudessa näytteille tehtiin kahdenlaisia mittauksia. Molekyylejä tutkittuun ensiksi lentoaikamassaspektrometrian avulla käyttäen eri fotonin energioita. Lisäksi tehtiin koinssidenssimittauksia, joissa havaitaan samaan ionisaatiotapahtumasta lähtevä fotoelektroni ja ioni. Tällöin saadaan tietoa ionisoituneen elektronin alkutilan vaikutuksesta molekyylin hajoamiskanavaan. Tulosten perusteella molemmilla molekyyleillä hajoaminen alkaa usein NO2-ejektiolla, mihin liittyy pieni fotoelektronin sidosenergia. Tätä lukuunottamatta funktionaalisen ryhmän vaihtuminen johtaa hyvin erityyppisiin hajoamiskanaviin ja PEPICO-karttoihin. Tulosten perusteella 1-(2,3-epoksipropyyli)-2-nitroimidatsolilla voi mahdollisesti olla sädeherkistäviä ominaisuuksia kuten misonidatsolillakin

Fragmentation Patterns of Radiosensitizers Metronidazole and Nimorazole upon Valence Ionization

We study gas-phase photodissociation of radiosensitizer molecules nimorazole and metronidazole with the focus on the yield of the oxygen mimics nitrogen oxides and nitrous acid. Regardless of photon energy, we find the nimorazole cation to split the intramolecular bridge with little NO2 or NO production, which makes the molecule a precursor of dehydrogenated methylnitroimidazole. Metronidazole cation, on the contrary, has numerous fragmentation pathways with strong energy dependence. Most notably, ejection of NOOH and NO2 takes place within 4 eV from the valence ionization energy. Whereas the NO2 ejection is followed by further fragmentation steps when energy so allows, we find emission of NOOH takes place in microsecond time-scales and as a slow process that is relevant only when no other competing reaction is feasible. These primary dissociation characteristics of the molecules are understood by applying the long-known principle of rapid internal conversion of the initial electronic excitation energy and by studying the energy minima and the saddle points on the potential energy surface of the electronic ground state of the molecular cation

Energy-dependent timescales in the dissociation of diiodothiophene dication.

Photodissociation molecular dynamics of gas-phase 2,5-diiodothiophene molecules was studied in an electron-energy-resolved electron-multi-ion coincidence experiment performed at the FinEstBeAMS beamline of MAX IV synchrotron. Following the photoionization of the iodine 4d subshell and the Auger decay, the dissociation landscape of the molecular dication was investigated as a function of the Auger electron energy. Concentrating on an major dissociation pathway, C4H2I2S2+ → C4H2S+ + I+ + I, and accessing the timescales of the process via ion momentum correlation analysis, it was revealed how this three-body process changes depending on the available internal energy. Using a generalized secondary dissociation model, the process was shown to evolve from secondary dissociation regime towards concerted dissociation as the available energy increased, with the secondary dissociation time constant changing from 1.5 ps to 129 fs. The experimental results were compared with simulations using a stochastic charge-hopping molecular mechanics model. It represented the observed trend and also gave a fair quantitative agreement with the experiment

Photodissociation dynamics of halogenated aromatic molecules : The case of core-ionized tetrabromothiophene

We studied the gas-phase photodissociation of a fully halogenated aromatic molecule, tetrabromothiophene, upon core-shell ionization by using synchrotron radiation and energy-resolved multiparticle coincidence spectroscopy. Photodynamics was initiated by the selective soft X-ray ionization of three elements-C, S, and Br-leading to the formation of dicationic states by Auger decay. From a detailed study of photodissociation upon Br 3d ionization, we formulate a general fragmentation scheme, where dissociation into neutral fragments and a pair of cations prevails, but dicationic species are also produced. We conclude that dicationic tetrabromothiophene typically undergoes deferred charge separation (with one of the ions being often Br+) that may be followed by secondary dissociation steps, depending on the available internal energy of the parent dication. Observations suggest that the ejection of neutral bromine atoms as the first step of deferred charge separation is a prevailing feature in dicationic dissociation, although sometimes in this step the C-Br bonds appear to remain intact and the thiophene ring is broken instead. Ionization-site-specific effects are observed particularly in doubly charged fragments and as large differences in the yields of the intact parent dication. We interpret these effects, using first-principles calculations and molecular dynamics simulations of core-hole states, as likely caused by the geometry changes during the core-hole lifetime

Photodissociation of bromine-substituted nitroimidazole radiosensitizers

Heavy elements and some nitroimidazoles both exhibit radiosensitizing properties through different mechanisms. In an effort to see how the overall radiosensitivity might be affected when the two radiosensitizers are combined in the same molecule, we studied the gas-phase photodissociation of two brominated nitroimidazoles and a bromine-free reference sample. Synchrotron radiation was employed to initiate the photodynamics and energy-resolved multiparticle coincidence spectroscopy was used to study the ensuing dissociation. We observed the brominated samples releasing high amounts of potentially radiosensitizing fragments upon dissociation. Since bromination also increases the likelihood of the drug molecule being ionised per a given X-ray dose, we conclude that heavy-element substitution of nitroimidazoles appears to be a viable path towards new, potent radiosensitizer drugs

Photodissociation dynamics of halogenated aromatic molecules:the case of core-ionized tetrabromothiophene

Abstract We studied the gas-phase photodissociation of a fully halogenated aromatic molecule, tetrabromothiophene, upon core–shell ionization by using synchrotron radiation and energy-resolved multiparticle coincidence spectroscopy. Photodynamics was initiated by the selective soft X-ray ionization of three elements — C, S, and Br — leading to the formation of dicationic states by Auger decay. From a detailed study of photodissociation upon Br 3d ionization, we formulate a general fragmentation scheme, where dissociation into neutral fragments and a pair of cations prevails, but dicationic species are also produced. We conclude that dicationic tetrabromothiophene typically undergoes deferred charge separation (with one of the ions being often Br⁺) that may be followed by secondary dissociation steps, depending on the available internal energy of the parent dication. Observations suggest that the ejection of neutral bromine atoms as the first step of deferred charge separation is a prevailing feature in dicationic dissociation, although sometimes in this step the C—Br bonds appear to remain intact and the thiophene ring is broken instead. Ionization-site-specific effects are observed particularly in doubly charged fragments and as large differences in the yields of the intact parent dication. We interpret these effects, using first-principles calculations and molecular dynamics simulations of core-hole states, as likely caused by the geometry changes during the core-hole lifetime