Herein is described our synthetic efforts toward the synthesis of (±)-nakadomarin A, a member of the manzamine alkaloids. The first chapter describes the isolation and biological significance of (–)-nakadomarin A. Chapter 2 describes the previous total syntheses as well as other partial syntheses of both (–)-nakadomarin A and its unnatural enantiomer. Chapter 3 discusses our approach to the formation of rings A and B in nakadomarin, as well as the installation of the quaternary center and the regioselective incorporation of a hydrazine moiety. Chapter 4 contains the development of a new methodology for the cleavage of hydrazine N-N bonds situated alpha to a carbonyl functionality. Chapter 5 describes the formation of rings D and E. Chapter 6 consists of experimental details and characterization data for all new compounds. / text

Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.

Thesis (Ph. D.)--West Virginia University, 2001. / Title from document title page. Document formatted into pages; contains ix, 82 p. : ill. Includes abstract. Includes bibliographical references (p. 70-80).

Thesis (M.S.)--Florida State University, 2005. / Advisor: Albert E. Stiegman, Florida State University, College of Arts and Sciences, Dept. of Chemistry and Biochemistry. Title and description from dissertation home page (viewed Jan. 24, 2006). Document formatted into pages; contains xiv, 89 pages. Includes bibliographical references.

Indiana University-Purdue University Indianapolis (IUPUI) / Metallopeptides of the general form M(II)∙Gly1-Gly2-His induce DNA strand scission via minor groove interactions. This peptide system can serve as a nucleic acid-targeted cleavage agent – either as an appendage to other DNA binding agents, or as a stand alone complex. In an effort to further our knowledge of DNA recognition and cleavage, a novel series of phenyl-benzimidazole modified Gly-Gly-His-derived metallopeptides was synthesized via solid phase methods and investigated. The new systems allow the formation of additional contacts to the DNA minor groove through the incorporation of a DNA binding phenyl-benzimidazole moiety, thus strengthening the overall binding interaction and further stabilizing the metal complex-DNA association. In addition, how Lys side chains and an amidinium group influence the efficiency of DNA cleavage was also studied. DNA cleavage studies suggested that the phenyl-benzimidazole-modified Gly-Gly-His metallopeptides possess enhanced DNA cleavage abilities. In particular, when amidines are placed on the benzimidazole moieties, these moieties appeared to play an important role in increasing the DNA cleavage activity of the metal complex, most likely through an enhanced electrostatic attraction to the DNA.

本論文主要研究銥和銠卟啉絡合物與鹵代苯 (ArX, X = Cl, Br, I)的碳-鹵鍵(Ar-X)的斷裂反應及其應用。本論文分為四個部分：（1）銠卟啉絡合物與鹵代苯(ArX, X = Cl, Br, I)之間的碳-鹵鍵(Ar-X)斷裂反應；（2）氟氯化苯的碳-氟鍵(Ar-F)與碳-氯鍵(Ar-Cl)斷裂的競爭反應；（3）氟取代基對金屬（銥和銠）-芳香碳(M-Ar)鍵強弱的影響；以及（4）銥卟啉氟硼荧絡合物的合成。 / 第一部分闡述了銠卟啉絡合物(Rh(ttp)Cl)與鹵代苯(ArX, X = Cl, Br, I) 之間的碳-鹵鍵 (Ar-X) 斷裂反應以及反應機理。在鹼性條件下，無論富電子還是缺電子的鹵代苯都能與Rh(ttp)Cl反應，生成Ar-X鍵斷裂的產物──銠卟啉芳基絡合物(Rh(ttp)Ar) 。機理研究顯示， Rh(ttp)Cl 首先與氫氧根離子反應生成Rh(ttp)OH，進而通過二聚反應生成[Rh(ttp)]₂。[Rh(ttp)]₂在加熱條件下與Rh(ttp)自由基可以互相轉化，產生的Rh(ttp)自由基與鹵代苯進行原位取代反應，生成銠卟啉芳基絡合物(Rh(ttp)Ar)和鹵素自由基。鹵素自由基可以和另一個Rh(ttp)自由基反應生成Rh(ttp)X，在氫氧根離子存在的條件下，Rh(ttp)X將再次轉化為Rh(ttp)OH繼續反應。 / 第二部分描述了氟氯化苯中碳-氟鍵(Ar-F)與碳-氯鍵(Ar-Cl)斷裂的競爭反應。機理研究顯示碳-氟鍵(Ar-F)斷裂的中間體是M(por)⁻，而碳-氯鍵(Ar-Cl)斷裂的中間體是MII(por)。因此，我們可以通過改變反應條件而控制生成物。例如，在較低溫度下和強鹼性的極性溶劑中，以M(por)⁻前體作為反應物，可以獲得較多的碳-氟鍵(Ar-F)斷裂的產物；而在較高溫度下和弱鹼性的非極性溶劑中，可以獲得較多的碳-氯鍵(Ar-Cl)斷裂的產物。 / 第三部分敘述了間位氟取代基對金屬-芳香碳(M-Ar)鍵的增強作用。有間位氟取代基的金屬（銥，銠）卟啉芳基絡合物(M(ttp)ArF)是最穩定的同分異構體。在250°C條件下，當反應30天後，Ir(ttp)C₆H₄F的三個異構體達到平衡狀態，其鄰位:間位:對位的比例大約為0:5:1。理論計算的結果也顯示Ir(ttp)(3-fluorophenyl)相對Ir(ttp)(2-fluorophenyl)和Ir(ttp)(4-fluorophenyl)有更低的能量。氟取代基在鄰位時，氟與卟啉之間空間位阻較大，減弱了金屬-芳香碳(M-Ar)鍵的鍵能。與氟取代基在對位相比，在間位時具有更好的吸電子效應，從而增加了金屬-芳香碳(M-Ar)鍵的極性，增強了金屬-芳香碳(M-Ar)鍵鍵能。 / 第四部分描述了利用碳-鹵鍵 (Ar-X) 的斷裂，合成銥卟啉氟硼荧絡合物的反應。銥卟啉氟硼荧絡合物的產率可以達到70%。銥卟啉氟硼荧絡合物在生物成像和放射療法都有潛在的應用。銥卟啉氟硼荧絡合物是用金屬自由基與氟硼荧反應合成的。 / This thesis focuses on the reaction scopes, mechanistic investigations and applications of base-promoted aryl carbon-halogen (Ar-X) bond cleavage with iridium and rhodium porphyrin complexes. This thesis is divided into four parts: (1) Ar-X (X = Cl, Br, I) bond cleavage with Rh(ttp)Cl; (2) competitive Ar-F and Ar-Cl bond cleavage with iridium and rhodium porphyrins; (3) fluorine substituent effect on the M-Ar (M = Ir, Rh) bond strength; and (4) synthesis of iridium porphyrin BODIPY complexes. / Part I describes the reaction scopes and mechanism of Ar-X (X = I, Br, Cl) bond cleavage with Rh(ttp)Cl (ttp = 5,10,15,20-tetratolylporphyrinato dianion). Under basic conditions, both electron-rich and electron-deficient ArX undergo Ar-X bond cleavage to give Rh(ttp)Ar in good yields. [with diagram] / The mechanistic investigations suggest that RhIII(ttp)Cl first undergoes ligand substitution by OH- to give RhIII(ttp)OH, which forms [RhII(ttp)]₂ through reductive dimerization. RhII(ttp) radical, which is in equilibrium with [RhII(ttp)]₂, cleaves the Ar-X (X = I, Br, Cl) bond through metalloradical ipso-substitution and gives RhIII(ttp)Ar and X radical. X radical recombines with another RhII(ttp) radical to generate RhIII(ttp)X, which gives back RhIII(ttp)OH through ligand substitution by OH-. [with diagram] / Part II describes the competitive Ar-F and Ar-X (X = Cl, Br) bond cleavage reactions of fluorochlorobenzenes with iridium and rhodium porphyrin complexes. Mechanistic studies suggest that M(por)⁻ is the intermediate for the Ar-F bond cleavage while MII(por) is the intermediate for the Ar-X bond cleavage. By taking advantage of the difference in mechanisms of the Ar-F and Ar-X bond cleavages, the selectivity of bond cleavage can be controlled by varying the reaction conditions. The Ar-F bond cleavage is favored in a polar solvent with a stronger base at lower temperatures with M(por)⁻ precursor, and the Ar-X bond cleavage is favored under non-polar conditions with a weaker base and at higher temperatures. [with diagram] / Part III describes the meta-fluorine substituent effect on strengthening the M-Ar (M = Ir, Rh) bond of M(ttp)ArF. M(ttp)ArF with meta-fluorine substituent are the most stable isomers among the isomeric Ar-H bond cleavage products. At 250 °C for 30 days, the three isomers of Ir(ttp)C₆H₄F reached an equilibrium with o : m : p = 0 : 5 : 1. The theoretical calculations also suggest that Ir(ttp)(3-fluorophenyl) is of lower energy than Ir(ttp)(2-fluorophenyl) and Ir(ttp)(4-fluorophenyl). The ortho-fluorine substituent exhibits steric effect which weakens the M-Ar bond. The meta-fluorine, which is more electron-withdrawing than para-fluorine, enhances the polarity of the M-C(ipso) bond and thus strengthens the M-Ar bond. [with diagram] / Part IV describes the application of Ar-I bond cleavage with Ir(ttp)(CO)Cl in synthesizing iridium porphyrin boron-dipyrromethene (BODIPY) complexes, which are potential photosensitizers for biological imaging and photodynamic therapy. The clinically interested iridium porphyrin BODIPY complexes have been prepared by a radical process of metalloradical with BODIPY. [with diagram] / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Qian, Yingying. / Thesis (Ph.D.) Chinese University of Hong Kong, 2014. / Includes bibliographical references. / Abstracts also in Chinese.

Thesis (Ph. D.)--Ohio State University, 2006. / Available online via OhioLINK's ETD Center; full text release delayed at author's request until 2007 Aug 15.

Title from PDF of title page (University of Missouri--Columbia, viewed on Feb 18, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Thesis advisor: Dr. Stephen Lombardo. Includes bibliographical references.

The topical application of sunscreens is widely practised to protect healthy and photosensitive skins from the sun. The benzophenone-derived sunscreens, e.g. 2-hydroxy-4-methoxy benzophenone-5-sulphonic acid (or benzophenone-4) and 2-hydroxy-4-methoxy benzophenone (or benzophenone-3), were ranked as the second and third most frequently used sunscreens, respectively, by the United States Food and Drug Administration (FDA) in 1996. These sunscreens are categorised as being 'safe' and 'effective'. However, it is well known that the parent compound, benzophenone, undergoes rapid hydrogen abstraction reactions on irradiation and is an extremely powerful radical generator. In addition, benzophenone has been shown to be a potent photosensitizer of thymine dimers in deoxyribose nucleic acid (DNA). More astounding to the sunscreen industry is the recent discovery that a group of non-steroidal anti- inflammatory drugs (NSAIDs) having the benzophenone backbone, e.g. ketoprofen, not only form thymine dimers when irradiated with DNA in vitro, but also photosensitize double stranded supercoiled DNA making it prone to single-strand break formation. Both these lesions, if unrepaired, may contribute to mutagenesis, carcinogenesis, inherited disease and eventually cell death. The purpose of this investigation was to determine if a group of benzophenone-derived sunscreen agents has the ability to photosensitize the cleavage of DNA, whereby supercoiled DNA is converted to the relaxed circular and linear forms. The group of UV absorbers investigated in this study included benzophenone-4, benzophenone-3 , 2,4 dihydroxybenzophenone (or benzophenone-l), 2,2'-dihydroxy-4,4'-dimethoxy benzophenone sulphonic acid (or trade name Uvinul DS49) and 2-phenylbenzimidazole-5-sulphonic acid (or trade name Eusolex 232). For comparison the parent compound benzophenone and the NSAID ketoprofen, a well-known photocleaver, were also studied. Buffered aqueous solutions of the benzophenones were irradiated in the presence of DNA at wavelengths greater than 300 nm with an Osram 500 W/2 high-pressure mercury lamp in conjunction with a 10 mm thick Pyrex filter. The irradiated samples were analysed for DNA cleavage by agarose gel electrophoresis and for DNA binding by fluorescence spectroscopy. The photostability of the UV absorbers was also investigated. In addition, computational studies were conducted to obtain the lowest energy geometrical structures of these UV absorbers and hence determine if intercalation of these UV absorbers with DNA was possible. From the photostability experiments conducted, it is apparent that the benzophenone-based UV absorbers were stable to photodecomposition when irradiated with UV light. They behaved in a manner different from their parent compound benzophenone, and from ketoprofen, where substantial photodegradation occurred upon UV irradiation. This is indicative of the rapid photoreactivity of the benzophenone backbone. The relative photostability of the UV absorbers was not anticipated and was attributed to the substituents present on the benzophenone backbone. The agarose gel electrophoresis experiments however clearly showed that benzophenone, ketoprofen, benzophenone-l, Uvinul DS49 and Eusolex 232 cleave ?X174 DNA when irradiated with UV light at wavelengths greater than 300 nm, while benzophenone-3 and benzophenone-4 did not. For these UV absorbers with the exception of benzophenone-3 and benzophenone-4, the number of single strand breaks in the DNA increased compared to when it was irradiated in their absence. In addition, the supercoiled DNA was converted to the relaxed circular and linear forms, the latter of which was undetected in the absence of the UV absorbers. Binding of benzophenone, ketoprofen, benzophenone-l and Uvinul DS49 to calf thymus DNA was also detected by the fluorescence spectroscopy technique. However, this was not observed for Eusolex 232, benzophenone-3 and benzophenone-4, since they did not compete with ethidium bromide for DNA binding sites. Where DNA cleavage did occur, the mechanism of this interaction had to be determined hence the motivation for the computational studies. From computational studies using PM3 semi- empirical calculations, it was determined that the benzophenone-based UV absorbers investigated, apart from Eusolex 232, displayed non-planar geometrical structures. This indicated that DNA intercalation of these sunscreen agents with DNA would at best be very limited, since only one half of the molecule could possibly interact with the bases of DNA. For benzophenone, ketoprofen, benzophenone-l and Uvinul DS49, photosensitised type I and type II processes involving triplet energy transfer reactions has been identified in literature as being responsible for DNA cleavage. It was determined by ab initio calculations that Eusolex 232 exists in a planar structure unlike the other UV absorbers mentioned above that were non- planar. It was concluded that although Eusolex 232 has the ability to intercalate with the base pairs of DNA, it does not do so, as shown by its lack of binding to calf thymus DNA by the fluorescence spectroscopy study. Literature alludes to photooxidation by singlet oxygen in single stranded DNA via the type II reaction and type I electron transfer reactions in double stranded DNA as the mechanism responsible for DNA cleavage induced by Eusolex 232. / Thesis (M.Sc.)-University of Natal, Durban, 2003.

Cheung, Chi Wai. / "December 2010." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.