This paper introduces the Bodymind model of Art Therapy and delineates the processes through which it has salutary effects on individuals coping with a variety of health related challenges. The goal of this model is to articulate how activation, reorganization, growth and reintegration of the self can emerge from bodymind processes activated by art therapy. It provides a framework for the conduct of research that will test the key theoretical mechanisms through which art therapy benefits clients. We expect this model to be a spring board for discussion, debate and development of the profession of art therapy. Furthermore, we hope readers can use this model to conduct sound mechanistic studies. This paper can inform social scientists and medical professionals on the manner in which art making can contribute to health.

<p> Dicobalt octacarbonyl reacts with a wide variety of molecules containing trichloromethyl functionalities to yield carbynyl tricobalt nonacarbonyl clusters of the general formula R-CCo 3 (CO) 9 . While these clusters have been shown to undergo many reactions, mechanistic studies on these systems are sparse. In particular, their rather facile decarbonylation processes are not well understood. </p> <p> Complexes of the type Ar-CO-CCo 3 (CO)9 readily lose CO to produce the corresponding Ar-CCo 3 (C0) 9 clusters but the origin of the carbon monoxide extruded was not known . Speculation had focussed on two possibilities: firstly, direct elimination of the ketonic carbonyl - perhaps via radical intermediates - and, secondly, via initial loss of a cobalt carbonyl ligand (to produce a 16-electron cobalt vertex) with subsequent migration of the original ketonic group onto the coordinatively unsaturated cobalt center. These two mechanistic possibilities are differentiable by labelling either the cobalt carbonyl sites or the ketonic position with carbon-13 and then examining the decarbonylated product to locate the isotopically enriched positions by 13c NMR spectroscopy. It is shown that the carbon monoxide initially eliminated is a cobalt carbonyl and the ketonic CO migrates from its apical position onto a cobalt atom. </p> <p> A second project involves the synthesis and characterization of a cobalt cluster derived from the reaction of dicobalt octacarbonyl with the insecticide DDT . This cluster contains the bis(4-chlorophenyl)methylcarbynyl capping group which is so bulky that it has the potential to stop the rotation of the carbynyl ligand and also prevent carbonyl exchange on the metal triangle. The DDT-tricobalt cluster was characterized by X-ray crystallography. The compound crystallizes in the space group P21/n: the monoclinic cell has dimensions a = 13.083 A, b = 14.222 A, c = 14.165 A, B = 95.871 degrees and Z = 4. The molecule adopts almost Cs symmetry except that the phenyl rings are twisted slightly so as to destroy the potential mirror plane. At low temperature, the cobalt carbonyl ligands are non-equivalent on the NMR time-scale and the possible causes for this behaviour are discussed. </p> / Thesis / Master of Science (MSc)

<p> A detailed study of the photoaddition of 3-phenylcyclohex- 2-enone and 2,3-dimethylbut-2-ene was undertaken in order to gain mechanistic information of the photochemistry of this enone. Photoadditions of this enone with cyclopentene, norbornene, and but-2-ene were also studied. Sensitization experiments showed that photoaddition with 2,3-dimethylbut-2-ene occurs when triplet sensitizers such as Michler's ketone or 2-acetonaphthone are used. The sensitized reactions are less efficient than the direct irradiation, except at infinite 2,3-dimethylbut-2-ene concentration, when the quantum yields for direct and sensitized processes are the same. This quantitative result may be explained by (a) inefficiency in the energy-transfer process from the sensitizer to enone 0 or (b) two excited states of enone being involved in the direct and sensitized processeso There are evidences that the excited state involved in the direct irradiation could possibly be the second triplet of the enoneo The presence of a higher enone tTiplet (T2) was established by the observed dimerization of norbornene. Cis-trans isomerization of but-2-ene was observed during photoaddition, which could also be attributed to a higher triplet, or to a 1,4-diradical intermediates Quenching studies provided an estimate of the lifetime of the reactive excited state in the direct irradiation. The energies of the electronic states of the enone were estimated from spectroscopic and chemical measurements. The formation of an enoneoolefin 1,4-diradical has been proposed to explain the effect of olefin concentration on the photoaddition. </p> / Thesis / Doctor of Philosophy (PhD)

Yes / Nanocrystalline hydroxyapatite (nanoHA) is the main hard component of bone and has potential to be used to promote osseointegration of implants and to treat bone defects. Here, using active pharmaceutical ingredients (APIs) like ibuprofen, we report on the prospects of combining nanoHA with biologically active compounds to improve the clinical performance of these treatments. In this study we designed and investigated the possibility of API attachment to the surface of nano-HA crystals via the formation of a hydrogen-bonded complex. The mechanistic studies of an ibuprofen/nanoHA complex formation have been performed using a holistic approach encompassing spectroscopic (FT-IR and Raman) and X-ray diffraction techniques as well as quantum chemistry calculations (DFT), while comparing the behaviour of the ibuprofen/nanoHA complex with that of a physical mixture of the two components. Whereas ibuprofen exists in dimeric form both in solid and liquid state, our study showed that the formation of the ibuprofen/nanoHA complex most likely occurs via the dissociation of the ibuprofen dimer into monomeric species promoted by ethanol, with subsequent attachment of a monomer to the HA surface. An adsorption mode for this process is proposed; this includes hydrogen bonding of the hydroxyl group of ibuprofen to the hydroxyl group of the apatite, together with the interaction of the ibuprofen carbonyl group to an HA calcium centre. Overall, this mechanistic study provides new insights into the molecular interactions between APIs and the surfaces of bioactive inorganic solids and sheds light on the relation between the non-covalent bonding and drug release properties. / Authors would like to acknowledge funding support from EPSRC (EP/L027011/1, EP/K029592/1). This research was performed in part at the MIDAS Facility, at the University of Sheffield, which was established with support from the Department of Energy and Climate Change.

Palladium-catalyzed reactions for carbon-carbon bond formation have had a significant impact on the field of organic chemistry in recent decades. Illustrative is the 2010 Nobel Prize, awarded for “palladium-catalyzed cross couplings in organic synthesis”, and the numerous applications of these transformations in industrial settings. This thesis describes recent developments in C(sp2)-C(sp3) bond formation, focusing on alkane arylation reactions and arylative dearomatization transformations. In the first part, our contributions to the development of intramolecular C(sp3)-H arylation reactions from aryl chlorides are described (Chapter 2). The use of catalytic quantities of pivalic acid was found to be crucial to observe the desired reactivity. The reactions are highly chemoselective for arylation at primary aliphatic C-H bonds. Theoretical calculations revealed that C-H bond cleavage is facilitated by the formation of an agostic interaction between the palladium centre and a geminal C-H bond. In the following section, the development of an alkane arylation reaction adjacent to amides and sulfonamides is presented (Chapter 3). The mechanism of C(sp3)-H bond cleavage in alkane arylation reactions is also addressed through an in-depth experimental and theoretical mechanistic study. The isolation and characterization of an intermediate in the catalytic cycle, the evaluation of the roles of both carbonate and pivalate bases in reaction mechanism as well as kinetic studies are reported. Our serendipitous discovery of an arylation reaction at cyclopropane methylene C-H bonds is discussed in Chapter 4. Reaction conditions for the conversion of cyclopropylanilines to quinolines/tetrahydroquinolines via one-pot palladium(0)-catalyzed C(sp3)-H arylation with subsequent oxidation/reduction are described. Initial studies are also presented, which suggest that this transformation is mechanistically unique from other Pd catalyzed cyclopropane ring-opening reactions. Preliminary investigations towards the development of an asymmetric alkane arylation reaction are highlighted in Chapter 5. Both chiral carboxylic acid additives and phosphine ligands have been examined in this context. While high yields and enantiomeric excesses were never observed, encouraging results have been obtained and are supported by recent reports from other research groups. Finally, in part two, the use of Pd(0)-catalysis for the intramolecular arylative dearomatization of phenols is presented (Chapter 7). These reactions generate spirocyclohexadienones bearing all-carbon quaternary centres in good to excellent yields. The nature of the base, although not well understood, appears to be crucial for this transformation. Preliminary results in the development of an enantioselective variant of this transformation demonstrate the influence of catalyst activation on levels of enantiomeric excess.

Palladium-catalyzed reactions for carbon-carbon bond formation have had a significant impact on the field of organic chemistry in recent decades. Illustrative is the 2010 Nobel Prize, awarded for “palladium-catalyzed cross couplings in organic synthesis”, and the numerous applications of these transformations in industrial settings. This thesis describes recent developments in C(sp2)-C(sp3) bond formation, focusing on alkane arylation reactions and arylative dearomatization transformations. In the first part, our contributions to the development of intramolecular C(sp3)-H arylation reactions from aryl chlorides are described (Chapter 2). The use of catalytic quantities of pivalic acid was found to be crucial to observe the desired reactivity. The reactions are highly chemoselective for arylation at primary aliphatic C-H bonds. Theoretical calculations revealed that C-H bond cleavage is facilitated by the formation of an agostic interaction between the palladium centre and a geminal C-H bond. In the following section, the development of an alkane arylation reaction adjacent to amides and sulfonamides is presented (Chapter 3). The mechanism of C(sp3)-H bond cleavage in alkane arylation reactions is also addressed through an in-depth experimental and theoretical mechanistic study. The isolation and characterization of an intermediate in the catalytic cycle, the evaluation of the roles of both carbonate and pivalate bases in reaction mechanism as well as kinetic studies are reported. Our serendipitous discovery of an arylation reaction at cyclopropane methylene C-H bonds is discussed in Chapter 4. Reaction conditions for the conversion of cyclopropylanilines to quinolines/tetrahydroquinolines via one-pot palladium(0)-catalyzed C(sp3)-H arylation with subsequent oxidation/reduction are described. Initial studies are also presented, which suggest that this transformation is mechanistically unique from other Pd catalyzed cyclopropane ring-opening reactions. Preliminary investigations towards the development of an asymmetric alkane arylation reaction are highlighted in Chapter 5. Both chiral carboxylic acid additives and phosphine ligands have been examined in this context. While high yields and enantiomeric excesses were never observed, encouraging results have been obtained and are supported by recent reports from other research groups. Finally, in part two, the use of Pd(0)-catalysis for the intramolecular arylative dearomatization of phenols is presented (Chapter 7). These reactions generate spirocyclohexadienones bearing all-carbon quaternary centres in good to excellent yields. The nature of the base, although not well understood, appears to be crucial for this transformation. Preliminary results in the development of an enantioselective variant of this transformation demonstrate the influence of catalyst activation on levels of enantiomeric excess.

The phenylalanine hydroxylase from Chromobacterium violaceum (CvPheH) is a non-heme iron monooxygenase that catalyzes the hydroxylation of phenylalanine. This study presents the use of kinetic isotope effects (KIE) as mechanistic probes to compare the reactivity of CvPheH and that of the eukaryotic aromatic amino acid hydroxylases. This study also describes the use of different spectroscopic and kinetic techniques to identify the hydroxylating intermediate for this enzyme and the assignment of the NMR backbone resonances of CvPheH. Kinetic isotope effects on aromatic and benzylic hydroxylation were used to establish that bacterial and eukaryotic phenylalanine hydroxylases have similar reactivity. The observed KIE on aromatic hydroxylation of 1.4 was shown to be a combination of an inverse isotope effect on the hydroxylation of the amino acid and a normal isotope effect on a subsequent step in the reaction. An isotope effect on benzylic hydroxylation of 10 was found for CvPheH. This result establishes the similar reactivity for CvPheH and the eukaryotic aromatic amino acid hydroxylases and suggests the involvement of a common hydroxylating intermediate. Kinetic isotope effects were used to study the hydroxylation of the aliphatic substrate cyclohexylalanine. The Dkcat value with [1,2,2,3,3,4,4,5,5,6,6-2H11]- cyclohexylalanine is unity with wild-type CvPheH, suggesting that chemistry is not ratelimiting with this substrate. The intramolecular isotope effect calculated using [1,2,3,4,5,6-2H6]-cyclohexylalanine yields a value of 14. This result is evidence for the involvement of a reactive iron species capable of abstracting a hydrogen atom from the aliphatic carbon in cyclohexylalanine. Analysis of the CvPheH reaction using freeze-quench Mössbauer spectroscopy allowed the detection of an Fe(IV) species in the first turnover of the enzyme. Chemical quench and stopped-flow spectrophotometric methods were used to establish the kinetic competency of the Fe(IV) intermediate as the hydroxylating species. The NMR amide backbone resonances in the HSQC spectrum of CvPheH were assigned to the corresponding amino acid residues using a suite of TROSY-based threedimensional triple resonance experiments. We were able to assign 224 residues out of the 278 assignable residues in CvPheH, this constitutes 81 percent of the assignable protein sequence.

DL-2-Amino-4-phosphonobutyric acid, an isostere of phosphoserine, was incorporated into the heptapeptide sequence, Leu-Arg-Arg-Ala-(DL-2-amino-4-phosphonobutyric acid)-Leu-Gly, for kinetic mechanistic studies of the cAMP-dependent protein kinase. To block the phosphono hydroxyl groups, methyl, ethyl and 4nitrobenzyl esters were studied as possible protecting groups. The phosphono diethyl ester of the N-Fmoc-protected amino acid was utilized in the synthesis of the heptapeptide. Two configurational forms of the protected peptide were obtained and were separated by C18-reverse phase HPLC. Characterization of the two isomeric forms was accomplished by 3 1P NMR, 1H NMR, 13C% NMR and amino acid analysis. The protecting groups of the isomeric phsophonopeptides were removed by HBr/AcOH and purified by cation exchange HPLC. Both phosphonopeptides were found to be inhibitors of the cAMP-dependent protein kinase, having Ki values of 0.6 mM (peptide A) and 1.9 mM (peptide B).

Palladium-catalyzed reactions for carbon-carbon bond formation have had a significant impact on the field of organic chemistry in recent decades. Illustrative is the 2010 Nobel Prize, awarded for “palladium-catalyzed cross couplings in organic synthesis”, and the numerous applications of these transformations in industrial settings. This thesis describes recent developments in C(sp2)-C(sp3) bond formation, focusing on alkane arylation reactions and arylative dearomatization transformations. In the first part, our contributions to the development of intramolecular C(sp3)-H arylation reactions from aryl chlorides are described (Chapter 2). The use of catalytic quantities of pivalic acid was found to be crucial to observe the desired reactivity. The reactions are highly chemoselective for arylation at primary aliphatic C-H bonds. Theoretical calculations revealed that C-H bond cleavage is facilitated by the formation of an agostic interaction between the palladium centre and a geminal C-H bond. In the following section, the development of an alkane arylation reaction adjacent to amides and sulfonamides is presented (Chapter 3). The mechanism of C(sp3)-H bond cleavage in alkane arylation reactions is also addressed through an in-depth experimental and theoretical mechanistic study. The isolation and characterization of an intermediate in the catalytic cycle, the evaluation of the roles of both carbonate and pivalate bases in reaction mechanism as well as kinetic studies are reported. Our serendipitous discovery of an arylation reaction at cyclopropane methylene C-H bonds is discussed in Chapter 4. Reaction conditions for the conversion of cyclopropylanilines to quinolines/tetrahydroquinolines via one-pot palladium(0)-catalyzed C(sp3)-H arylation with subsequent oxidation/reduction are described. Initial studies are also presented, which suggest that this transformation is mechanistically unique from other Pd catalyzed cyclopropane ring-opening reactions. Preliminary investigations towards the development of an asymmetric alkane arylation reaction are highlighted in Chapter 5. Both chiral carboxylic acid additives and phosphine ligands have been examined in this context. While high yields and enantiomeric excesses were never observed, encouraging results have been obtained and are supported by recent reports from other research groups. Finally, in part two, the use of Pd(0)-catalysis for the intramolecular arylative dearomatization of phenols is presented (Chapter 7). These reactions generate spirocyclohexadienones bearing all-carbon quaternary centres in good to excellent yields. The nature of the base, although not well understood, appears to be crucial for this transformation. Preliminary results in the development of an enantioselective variant of this transformation demonstrate the influence of catalyst activation on levels of enantiomeric excess.

Olefin metathesis is a valuable synthetic tool, widely used in several fields of science. Due to the importance of this transformation several contributions have been made in this field in order to understand mechanistic aspects, reactivity and applicability of this process. In this topic, ruthenium indenylidene complexes have shown great activity and stability in metathesis, making them very valuable pre-catalysts. However, several aspects of these pre-catalysts have not been evaluated yet. For example, even though reports of active second generation ruthenium indenylidene complexes bearing bulky N-heterocyclic carbenes are present in the literature, no studies have been done to understand how steric hindrance affects the process. For these reasons, [RuCl₂(IPr*)(PPh₃)(3-phenylindenylidene)] (IPr*-PPh₃) and [RuCl₂(IPr*)(Py)(3-phenylindenylidene)] (IPr*-Py), bearing the very bulky ligand, IPr* have been synthesised and compared with [RuCl₂(IPr)(PPh₃)(3-phenylindenylidene)] (IPr-PPh₃) and the new [RuCl₂(IPr)(Py)(3-phenylindenylidene)] (IPr-Py). Another important aspect, presented in this thesis, is the investigation of the stability of indenylidene pre-catalysts in alcohol solvents. Surprisingly, several different decomposition processes occur depending on the starting complex and the alcohol used. Mechanistic investigation into this decomposition, allowed us to develop a better understanding of this process, and to predict the decomposition product based on the environment. In particular, this study revealed that [RuCl(η⁵-3-phenylindenyl)(PPh₃)₂] (Eta-5) is accessed from [RuCl₂(3-phenylindenylidene)(PPh₃)₂] (M₁₀) via a novel indenylidene to η⁵-indenyl rearrangement. This formal decomposition product has been found to be active in at least 20 different catalytic transformations, rendering it a versatile catalytic tool.