published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

Nanosecond time-resolved resonance Raman (ns-TR3) spectroscopy was used in this thesis to study the photoreduction reactions and the photochemistry of chloro-substituted benzophenone (ClBP) triplets. The 3-chlorobenzophenone (3-ClBP), 4-chlorobenzophenone (4-ClBP) and 4,4′-dichlorobenzophenone (4,4′-diClBP) triplets exhibit similar properties to the parent BP triplet. In isopropyl alcohol (IPA), the hydrogen abstraction reactions were observed for the 3-ClBP, 4-ClBP and 4,4′-diDlBP triplets. The diphenylketyl (DPK) radicals produced from the hydrogen abstraction reactions were observed and the recombination of the DPK and dimethylketyl radicals at the para-position was observed to form a light absorption transient (LAT) species. In MeCN:H2O/1:1 aqueous solutions, these DPK radicals were also observed but with a slower formation rate and the LAT species was produced by reaction with OH radicals. Density functional theory (DFT) calculations were employed to help identify the intermediates seen in the TR3 spectra and to help provide information about the vibrational motions of the molecules examined. The 2-Cl-DPK radical was also observed in the TR3 spectra obtained in an IPA solvent. However, the yield of the 2-Cl-DPK radical and the hydrogen abstraction rate was observed to be significantly lower than that of the other ClBP examined here under the same experimental conditions. The results DFT calculations show that the 2-chloro substituent changes the geometry and the electron density of the molecular orbitals of the BP triplet so that the 2-chloro substituent reduces the hydrogen abstraction ability the triplet state, which is different the hypothesis put forward by some previous studies that an electron-withdrawing group should increase the photoreduction ability of BP derivatives. Norfloxacin (NF) and Enoxacin (EN) are representative derivatives of Fluoroquinolones (FQ). There are four forms of NF and EN and these different forms can coexist in aqueous solutions. The UV-vis absorption and resonance Raman (RR) spectra of NF and EN have been obtained in neat acetonitrile (MeCN), MeCN:HClO4-H2O/1:1 (pH?1), MeCN:H2O/1:1 (pH?7.5) and MeCN:NaOH-H2O/1:1 (pH?13) solutions. The species observed in the spectra are assigned by comparison of the experimental spectra to the DFT calculated spectra and the vibrational modes are also described from the results of the DFT calculations. The absorption spectra of NF and EN obtained in MeCN:H2O/1:1 solutions show that some other species coexist with the tautomeric forms in the neutral aqueous solution. The RR spectra of the tautomeric forms of NF and EN were obtained by subtraction of the RR spectra of the neutral and anionic forms from the RR spectra of NF and EN in neutral aqueous solutions. The results suggest that NF and EN exists in neutral, anionic and tautomeric forms in neutral aqueous solutions. The time dependant DFT calculation results suggest that the fluorine atom has little contribution to the lowest unoccupied molecular orbitals of the different forms of NF and EN. / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

Nanosecond time-resolved resonance Raman spectroscopy (ns-TR3), nanosecond transient absorption (ns-TA) and femtosecond transient absorption (fs-TA) were utilized to investigate the photochemistry of ketoprofen (KP), ketoprofen-purine dyads, fenofebric acid (FA) in different solutions. For KP, the rate constant and reaction mechanism of KP are strongly dependent on the concentration of water. In neat acetonitrile and acetonitrile-rich solutions (water:acetonitrile?1:1, v:v), KP exhibits mostly benzophenone-like photochemistry to give rise to triplet state which in turn transforms to ketyl radical intermediate by hydrogen abstraction reaction. However, in aqueous solutions with higher water ratios (water:acetonitrile?80%) or acidic solutions, fs-TA studies found that after the irradiation of KP the singlet state will transform into the triplet state with a high efficiency through an intersystem crossing and a triplet state mediated decarboxylation reaction of KP is confirmed in water-rich and acidic solutions as well as the triplet state KP- anion generating a KP carbanion through a decarboxylation reaction. Triplet state ketoprofen (3KP) is firstly observed by ns-TR3 experiments and then excited triplet state intramolecular proton transfer (ESIPT) induces 3KP to facilely undergo the decarboxylation reaction to generate a triplet protonated carbanion biradical (3BCH) species, this observation is also confirmed by the results from density functional theory (DFT) calculations. For solutions with higher water concentrations (such as between 50% and 90% water by volume), the hydrogen abstraction and decarboxylation processes are two competitive pathways with different rate constants. For KP-purine dyads, intramolecular hydrogen abstraction has been proposed to form ketyl-C1 biradical in acetonitrile solvent. Fs-TA study on KP-purine nucleoside dyads reveals that 3KP of cisoid dyads decays faster than 3KP of transoid dyads obtained in acetonitrile-water mixtures. Ns-TR3 experiments and DFT calculations suggest that ketyl-C1 biradical intermediate is generated with a higher efficiency for the 5-KP-dG dyad than for the 5-KP-dA and 5-KPGly-dA dyads. There is no ketyl-C1 biradical observed in ns-TR3 experiments for the 3-KP-dA dyad with transoid structure due to a steric effect. For FA, a solvent dependent photochemistry is observed. A typical nπ* triplet state FA (3FA) is evolved by a high efficient intersystem crossing in acetonitrile-rich solutions and subsequently 3FA promptly abstracts a hydrogen from water molecule to generate a ketyl radical intermediate. In contrast, an inversion of the hydrogen abstraction and decarboxylation reactions of nπ* 3FA is rationalized with the assistance of water molecules when going from acetonitrile-rich to water-rich mixtures. However, in 50% PBS solution, FA carbanion is observed from the picosecond to nanosecond times and the cleavage of FA carbanion gives rise to the enolate 3- anion at later nanosecond delay times. / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

Femtosecond time-resolved transient absorption (fs-TA), nanosecond time-resolved transient absorption (ns-TA), and nanosecond time-resolved resonance Raman spectroscopy (ns-TR3) methods were used to study the behaviors of the transient intermediates involved in the photophysical and photochemical processes of 3-methylbenzophenone (3-MeBP), 3-(hydroxymethyl)benzophenone (m-BPOH), and 2-(1-hydroxyethyl) 9,10-anthraquinone (2-HEAQ). A particular focus of this work was to study the unusual meta methyl activation reactions of these compounds in water-containing solutions. Density functional theory (DFT) calculations were conducted to help make assignments of the observed experimental transient species and to better understand the reaction mechanisms. First, the photophysical and photochemical reactions of m-BPOH were investigated in selected solvents. In acetonitrile (MeCN) the formation of the triplet state of m-BPOH, (denoted as (m-BPOH)3 ), was detected via an intersystem crossing (ISC). In 2-propanol (IPA), (m-BPOH)3 abstracted a hydrogen atom from the solvent molecule to form an aryl ketyl radical. In an acidic mixed aqueous solution at pH 2, the photoredox reaction appeared to be the predominant reaction. In a more acidic aqueous solution with [H+] =1.0 M, the photoredox reaction faced some competition from the overall photohydration reaction. Second, the photophysical and photochemical reactions of 2-HEAQ in MeCN, IPA, and neutral, acid and basic aqueous solutions were studied. The ISC process of 2-HEAQ took place in MeCN with generation of the triplet excited state species of 2-HEAQ, (2-HEAQ)3. In IPA solvent, (2-HEAQ)3 underwent a hydrogen abstraction with the solvent. A photoredox reaction takes place via an initial protonation process of the AQ group that is followed by deprotonation of the methylene C-H bond in aqueous solutions within a pH range from 2 to 10. Under a stronger acidic aqueous condition with [H+] =1.0 M, the photohydration reaction becomes the major reaction. In strong basic solutions (pH=12) only ISC was observed to take place. The unusual photoredox reaction takes place via protonation of the carbonyl oxygen first followed by deprotonation of the C-H bond in the side chain for both m-BPOH and 2-HEAQ. The protonation of the excited carbonyl oxygen group has been widely studied. On the other hand, the deprotonation of methylene C-H bond is unusual. Therefore, this photoredox reaction for m-BPOH and 2-HEAQ is termed as a meta methyl activation reaction. Third, the photophysical and photochemical reactions of 3-MeBP were explored and compared to those of 4-methylbenzophenone (4-MeBP). This work found that 3-MeBP and 4-MeBP exhibit similar behaviors with m-BPOH and 2-HEAQ in MeCN and IPA. In MeCN, both 3-MeBP and 4-MeBP undergo an efficient ISC process producing triplet excited state species, (3-MeBP)3 and (4-MeBP)3, respectively. In IPA, the (3-MeBP)3 and (4-MeBP)3 intermediates were quenched by the hydrogen abstraction reaction with the solvent. In acidic aqueous solutions (pH  2), the protonated carbonyl oxygen species (3-MeBPH+)3 and (4-(MeBPH+)3 are directly observed by fs-TA spectra. In the case of 4-MeBP, a photohydration is detected and the m-(4-MeBPH2O)3 and o-(4-MeBPH2O)1 species are observed. In contrast, an unusual meta methyl activation reaction is observed for 3-MeBP. In a stronger acid aqueous solution ([H+] =1.0 M) the meta methyl activation reaction becomes the predominant reaction. / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

No / A systematic identification of the degradation products of hydroxypropyl methylcellulose phthalate (HPMCP) during hot melt extrusion (HME) has been performed. A reverse phase HPLC method was developed for the extrudates of both hydroxypropyl methylcellulose acetate succinate (HPMCAS) and HPMCP polymers to quantify their thermal hydrolytic products: acetic acid (AA), succinic acid (SA) for HPMCAS and phthalic acid (PA) for HPMCP, without hydrolysing the polymers in strong alkaline solutions. The polymers were extruded in the temperature range of 160-190 degrees C at different screw rotation speeds and hydrolytic impurities were analysed. Investigation of extruded HPMCP showed an additional thermal degradation product, who is structural elucidation revealed to be phthalic anhydride (PAH). Moreover, two environmental analytical impurities, dimethyl phthalate and methyl benzoate formed in situ were recorded on GC-MS and their origin was found to be associated with PAH derivatization. Using the experimental data gathered during this study, a degradation mechanism for HPMCP is proposed.