The inclusion of atoms other than carbon into the framework of polycyclic conjugated hydrocarbons can have profound effects on the properties of the resultant compounds. Substitution of acenes with nitrogen-, oxygen-, and sulfur-containing rings has long been used as a strategy to alter the HOMO and LUMO energy levels of a compound and direct the solid-state morphology. In this thesis, I present my work in extending heteroatom substitution into the class of compounds known as indenofluorenes. Chapter I serves as an overview of indenofluorenes and related compounds with a special focus on the redox properties of these materials. Chapter II covers the synthesis and characterization of two selenophene-containing indenofluorene analogues. Chapter III discloses a new synthetic method for the preparation of unsymmetrical indenofluorenes and discusses the unusual reactivity of the dione precursors. Chapter IV is a comprehensive study of indacenodibenzothiophenes. This chapter investigates how heteroatom substitution affects the antiaromaticity of the indacene core and presents a detailed optoelectronic, computational, solid-state and materials study of a series of indacenodibenzothiophene derivatives. Chapter V presents my work towards the synthesis of the final unknown indenofluorene isomer, indeno[1,2-a]fluorene. Appendices A and B discuss my work done as part of Professor Shih-Yuan Liu’s research group at the start of my graduate career. This dissertation includes previously published and unpublished coauthored material. / 10000-01-01

京都大学 / 新制・課程博士 / 博士(理学) / 甲第23021号 / 理博第4698号 / 新制||理||1674(附属図書館) / 京都大学大学院理学研究科化学専攻 / (主査)准教授 齊藤 尚平, 教授 時任 宣博, 教授 依光 英樹 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

Texaphyrins represent the vanguard of experimental anticancer drugs and also symbolize a well-known example of expanded porphyrins, a class of oligopyrrolic macrocycles with tumor localization properties and powerful metal chelating properties. Chapter 1 of this thesis describes the unique structural characteristics of this complex synthetic molecule along with the biological relevance and scientific justifications for studying its anticancer properties and powerful MRI contrast ability. This Chapter also serves to underscore the need to improve further and refine the efficacy of texaphyrins as compounds that may be applied in the struggle against cancer. Chapter 2 details the synthesis of bismuth(III) and lead(II)-texaphyrin complexes that could potentially find use as [alpha]-core emitters for radiotherapy. In principle, porphyrins would ostensibly appear to be ideal ligands for use in radiotherapy due to their tumor-localizing ability. However, Bi(III)- and Pb(II)-porphyrin complexes are extremely rare, most reflecting the vastly challenging synthesis of these compounds as well as their general lack of stability. These limitations provided an incentive for us to use texaphyrins as more versatile ligands to prepare and fully characterize stable bismuth(III) and lead(II) complexes. To be of interest in future medical applications, we needed to prepare these complexes quickly as compared to the relevant time scales set by the half-lives of the isotopes targeted for use in radiotherapy. This goal was successfully realized. As mentioned above, texaphyrin is able to form stable complexes with a large variety of metals particularly in the lanthanide series. Gadolinium(III) complexes of texaphyrin have been studied in considerable detail. Chapter 3 details the synthesis and conjugation methods used to develop a texaphyrin conjugated dual mode nanoparticle contrast agent. This project has been done in collaboration with the group of Prof. Jinwoo Cheon (Yonsei University, Seoul, Korea), who demonstrated fascinating results with the texaphyrin functionalized nanoparticles. Not only do these conjugates act as improved magnetic resonance contrast agents displaying enhanced signals in both the T1 and T2 MRI modes, but also serve to sensitize apoptotic hyperthermia. It is this latter, double effector feature, that has been most extensively studied to date. Chapter 4 of this dissertation describes work done in close collaboration with Dr. Natalie Barkey and Dr. David Morse (Moffitt Cancer Center, Tampa, FL) where a gadolinium texaphyrin complex was developed that is able to target the melanocortin 1 receptor (MC1R) when encapsulated in a micellar system. As detailed in this Chapter, these collaborateurs demonstrated that these gadolinium-texaphyrin micelles are able to target MC1R-expressing xenograft tumors in vivo. This work relied on the supply of a new set of texaphyrin derivatives that were prepared and characterized as part of this dissertation work Chapter 5 of this disseration introduces sapphyrins, another class of expanded porphyrins with tumor selectivity. This project is based on the hypothesis that a direct linkage of sapphyrin with an anticancer agent based on ruthenium(II) could improve the efficacy of both compounds. Since sapphyrins exhibit limited ability to form stable complexes with transition metals, an appended 1,10-phenanthroline unit was chosen as an efficient N-donor aromatic ligand for ruthenium(II). Therefore, extensive synthetic efforts were made to form this sapphyrin-1,10-phenanthroline construct in an effort to stabilize a mixed sapphyrin-metallo-phenanthroline complex. Finally, Chapter 6 of this dissertation demonstrates the author's efforts to synthesize a planar rosarin species. Non-aromatic and non-planar rosarins have been known for over two decades. Through structural modification of the compound, namely through linking of both [Beta] positions on the bipyrrole unit, a new planar rosarin species has been synthesized exhibiting Hückel antiaromaticity. / text

The thesis entitled “Addressing subtle physicochemical features exhibited by molecular crystals via Experimental and Theoretical Charge Density Analysis” consists of five chapters. An introductory note provides a brief description of experimental and theoretical charge density methodology, followed by its utilization in obtaining certain physical and chemical properties in molecular crystals. Chapter 1 addresses not so easily accessed molecular property arising due to electron conjugation, highlighting antiaromaticity in tetracyclones. A systematic study of six tetracyclone derivatives with electron withdrawing and electron donating substituents has been carried out using experimental and theoretical charge density analysis. A three pronged approach based on quantum theory of atoms in molecules (QTAIM), nucleus independent chemical shifts (NICS), and source function (SF) has been employed to establish the degree of antiaromaticity of the central five-membered ring in all the derivatives. Electrostatic potentials mapped on the is density surface reveal the finer effects of different electron withdrawing and electron donating substituents on the carbonyl group. Chapter 2 presents a temperature induced reversible first order single crystal to single crystal phase transition (Room temperature Orthorhombic, P22121 to low temperature Monoclinic, P21) in a  hybrid peptide, Boc-γ4(R)Val-Val-OH. The thermal behavior accompanying the phase transition of the dipeptide crystal was characterized by differential scanning calorimetry, visual changes in birefringence of the sample during heating and cooling cycles on a hot-stage microscope with polarized light. Variable-temperature unit cell check measurements from 300 to 100 K showed discontinuity in the volume and cell parameters near the transition temperature, supporting the first-order behavior. The reversible nature of the phase transition is traced to be due to an interplay between enthalpy and entropy. Chapter 3 brings out an unusual stabilizing interaction involving a cooperative -hole and ¬hole character in a short NCS···NCS bond. This chapter describes structural features of four isothiocyanate derivatives, FmocXCH2NCS; X=Leu, Ile, Val and Ala. Among these it is observed that only FmocLeuCH2NCS which crystallizes in a tetragonal space group, P41, (a=b=12.4405(5) Å; c= 13.4141(8) Å) transforms isomorphously to a low temperature form, P41, (a=b=17.4665(1) Å; c= 13.1291(1) Å). The characteristics of the phase transition have been monitored by Differential Scanning Calorimetry, variable temperature IR and temperature dependent unit cell measurements. The short NCS···NCS intermolecular interaction (3.296(1) Å) is analyzed based on detailed experimental charge density analysis which reveals the nature of this stabilizing interaction. Chapter 4 explains a comparative study of syn and anti conformations of carboxylic acids in peptides from both structural aspect and charge density features. Single crystal structures of four peptides having syn conformations [BocLeuγ4(R)Valγ4(R)ValOH, BocLeuγ4(R)ValLeuγ4(R)ValOH, Boc3(S)Leu3(S)LeuOH] and one with anti conformation, BocLeuγ4(R)ValValOH have been analyzed. Experimental charge density analysis has been carried out exclusively on BocLeuγ4(R)ValValOH having anti form, because of its rare occurrence in literature. However, low temperature datasets on the four peptides with syn conformations were collected and theoretical charge density analysis has been carried out on two of these compounds. Electrostatic potentials mapped on is density surface bring out a significant difference at the oxygen atoms of the carboxyl group in the two conformations. However, lone pair orientation of different types of Oxygen atoms in the two forms (urethane, amide, acid) doesn’t exclusively indicate the differences in the corresponding charge density features. Chapter 5 addresses the issue of how sensitive are the charge density features associated with amino acid residues when the backbone conformational angles are varied. Three model systems, 1, L-alanyl–L-alanyl–L-alanine dehydrate; 2, anhydrous L-alanyl–L-alanyl–L¬alanine and 3, cyclo-(D,L-Pro)2(L-Ala)4 monohydrate have been chosen for this evaluation. Compound 1 has ant parallel alignment of tripe tide strands, and compound 2 has parallel alignment. All the alanine residues in compound 1 and 2 are in the -sheet region of the Ramachandran plot, whereas, the four Alanine residues in the cyclic hex peptide 3 span different regions of the Ramachandran plot. Theoretical multipole modelling has been carried out in order to explore the plausibility of transferring multipole parameters across different regions of Ramachandran Plot. Appendix I contains a brief description of charge shift bonding in Ph-CH2-Se-Se-CH2-Ph, as determined based on both experimental and theoretical charge density analysis. Appendix II contains a reprint of a published article on “Conformation-Changing Aggregation in Hydroxyacetone: A Combined Low-Temperature FTIR, Jet, and Crystallographic Study”.

This thesis presents a combined experimental and computational evaluation of the physical-organic properties of butadiyne-linked porphyrin oligomers. The principal result from the thesis is the synthesis and characterisation of the largest aromatic and antiaromatic systems to date, in the form of an oxidised [6]-porphyrin nanoring, with diameter 2.4 nm. This large electronically coherent system provides insight into the connection between aromatic ring currents and persistent currents in metal and semiconductor mesoscopic rings. Chapter 1 briefly reviews the concepts used in the remainder of the thesis, with a particular focus on aromaticity. In Chapter 2, the barrier to inter-porphyrin torsional rotation in a butadiyne-linked porphyrin dimer is determined computationally and experimentally to be 3 kJ mol^-1. The barrier height is closely related to the resonance delocalisation energy between the porphyrin subunits. In Chapter 3 we show that by oxidising a butadiyne-linked [6]-porphyrin nanoring to its 4+ and 6+ oxidation states, the nanoring becomes antiaromatic and aromatic respectively. In contrast, the neutral oxidation state exhibits only local aromaticity for the six porphyrin units. The 12+ cation can also be generated, and exhibits local antiaromaticity for each porphyrin unit. The characterisation of (anti)aromaticity employs NMR and computational techniques. In Chapter 4, the properties of cation radicals of linear and cyclic porphyrin oligomers are explored. Cations generated by spectroelectrochemistry are measured by optical spectroscopies, and chemically generated radical monocations are examined by cw/pulsed EPR spectroscopies. EPR and optical spectroscopies agree that the dimer monocation radical is fully delocalised, in Robin-Day Class III, whereas the monocations of longer oligomers are localised over 2-3 porphyrin units (Class II). In Chapter 5, photophysical and computational investigations into excited state aromaticity in porphyrin nanorings are presented. The computational results suggest the presence of aromaticity in the triplet excited states, but experiment fails to convincingly demonstrate the effect. Computational results in Chapter 6 show that a butadiyne linked [6]-porphyrin nanoring in which one butadiyne (C≡C-C≡C) is truncated to an alkyne (C≡C) exhibits a reversal of aromaticity and antiaromaticity in its oxidised states, compared to the all-butadiyne linked nanoring, consistent with Hückel's law.

xx, 318 p. ： ill. (some col.) / Highly conjugated, carbon rich molecules are of great interest due to their unique optoelectronic properties. These molecules are now recognized as suitable materials for advanced materials applications such as light-emitting diodes, photovoltaics, and thin film transistors. Of particular interest is the indenofluorene (IF) scaffold, a 6-5-6-5-6-fused ring system that holds a striking topological similarity to pentacene, a very successful electron donating organic semiconductor. Also of interest is another class of compounds referred to as tetrakis(arylethynyl)benzenes, TAEBs, which are cruciform-shaped molecules that possess numerous pathways for electronic and photonic transfer and are amenable to a host of substitution patterns. Chapter I examines the history of the IF scaffold and its development over the last century through the use of literature examples relating to both its synthesis and potential use as an emerging class of electron accepting materials. Chapter II introduces the feasibility of stable, fully conjugated IFs. Two examples of 5,6,11,12-tetraethynyl-indeno[1,2- b ]fluorenes are synthesized where their structural and optoelectronic properties are explored. Chapter III further explores the IF scaffold and outlines the synthesis of a series of 6,12-diethynylindeno[1,2-b ]fluorenes in conjunction with detailed computational, structural, and photophysical studies. Chapter IV discusses the synthesis and characterization of a series of 6,12-diarylindeno[1,2- b ]fluorenes and examines their structural and optoelectronic properties. Chapter V describes a series of donor/acceptor-functionalized TAEBs that incorporate the 4,4-difluoro-4-bora-3a,4a,-diaza-s -indacene moiety, better known as BODIPY, as the acceptor unit. Additionally, two TAEB molecules and three structurally related bis(arylethynyl)benzene (BAEB) isomers where only acceptors are used to evaluate the effectiveness of the donor group are synthesized. This dissertation includes both previously published and unpublished co-authored material. / Committee in charge: Professor David R. Tyler， Chairperson； Professor Michael M. Haley， Advisor； Professor Victoria J. DeRose， Member； Professor Shih-Yuan Liu， Member； Professor Scott D. Bridgham， Outside Member

The cyclopentadienone-fused dihydropyrenes 46 and 47 were synthesized. The internal methyl resonances, the coupling constants, NICS calculations and X-ray results confirmed that the cyclopentadienone displays antiaromatic character resulting in bond localization in the annulene ring consistent with a 4n-pi fused system. The ring current of the dihydropyrene fragment is reduced by fusion of the antiaromatic system by about 80% of that caused by benzene. The syntheses of the methylfulvene fused dihydropyrene 56 and the phenylfulvene fused dihydropyrene 58 have been accomplished. The calculated and experimental NMR data and NICS calculations all demonstrated that the fulvenes had weak diatropic ring currents and caused bond localizations in the DHP rings, in which phenyl fulvene has a larger effect than that of methyl fulvene. A number of bis-dihydropyrene systems, bis-dihydropyrene ketone 117, bis-benzo[e]dihydropyrene ketone 119, benzo[e]dihydropyrene dihydropyrene ketone 122, bis-benzo[e]dihydropyrene methylene 124 and the benzo[e]dihydropyrene- dihydropyrene acetylene 130, have been synthesized, in which 117, 119 and 124 are homo-systems and 122 and 130 are hetero-systems. The multiple photoswitching properties study found that all of these systems except 130 showed multi-states during the photo opening and photo closing processes, which means that each end of the DHP units photo opens or closes separately rather than synchronously. In the homo switches 117, 119 and 124, the two DHP units act independently, but the relative differentiation is not very significant. On the other hand, the hetero-switch 122 showed fully differentiated photo opening process and almost a pure open-closed intermediate 122’ could be achieved. This is the first example which clearly showed four states in the UV closing process. The relative photo opening and closing rates compared to benzoDHP 36 have also been studied. It was found that while the carbonyl linker largely increased the relative photo opening rate (117, 119 and 122), the methylene linker only increased it slightly (124). The photo closing processes were always fast as usual. The studies of the thermal return reactions of these systems showed that while the carbonyl linker substantially slowed down the thermal return reactions of the DHP units (117, 119 and 122), the methylene linker speeded it up slightly (124). The mono-iron tricarbonyl benzo[e]dihydropyrene complex 152, the bis-iron tricarbonyl benzo[e]dihydropyrene complex 153 and the iron tetracarbonyl dihydropyrene complex 151 were synthesized. The structures of 152 and 153 were determined by X-ray crystallography. The coordinations of iron tricarbonyl moieties to the DHP rings caused a distortion of ca. 30 degree away from the central DHP plane. Coordination also increased bond alternation and reduced ring currents in the DHP rings. 1H-NMR and X-ray studies showed that 152 showed a weak paratropic ring current in the DHP ring. Iron coordination of the DHP completely stopped the photochromic properties of the dihydropyrenes.

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