Rozprawy doktorskie na temat „Organoplatinum compounds”

Kliknij ten link, aby zobaczyć inne rodzaje publikacji na ten temat: Organoplatinum compounds.

Utwórz poprawne odniesienie w stylach APA, MLA, Chicago, Harvard i wielu innych

Wybierz rodzaj źródła:

Sprawdź 29 najlepszych rozpraw doktorskich naukowych na temat „Organoplatinum compounds”.

Przycisk „Dodaj do bibliografii” jest dostępny obok każdej pracy w bibliografii. Użyj go – a my automatycznie utworzymy odniesienie bibliograficzne do wybranej pracy w stylu cytowania, którego potrzebujesz: APA, MLA, Harvard, Chicago, Vancouver itp.

Możesz również pobrać pełny tekst publikacji naukowej w formacie „.pdf” i przeczytać adnotację do pracy online, jeśli odpowiednie parametry są dostępne w metadanych.

Przeglądaj rozprawy doktorskie z różnych dziedzin i twórz odpowiednie bibliografie.

1

Yang, Jun. "Carbonylation in organopalladium and organoplatinum compounds". Thesis, University of Sheffield, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286872.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
2

Griffiths, D. C. "Thermal rearrangements of organoplatinum (II) compounds". Thesis, Imperial College London, 1985. http://hdl.handle.net/10044/1/37713.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
3

Phelps, Jennifer. "Synthesis of homoleptic PT(0) acceptor phosphine complexes". Laramie, Wyo. : University of Wyoming, 2008. http://proquest.umi.com/pqdweb?did=1594481221&sid=1&Fmt=2&clientId=18949&RQT=309&VName=PQD.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
4

吳玉如 i Yuk-yu Ng. "Photophysical properties and photochemistry of organoplatinum (II) complexes". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1995. http://hub.hku.hk/bib/B31213534.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
5

Ng, Yuk-yu. "Photophysical properties and photochemistry of organoplatinum (II) complexes /". Hong Kong : University of Hong Kong, 1995. http://sunzi.lib.hku.hk/hkuto/record.jsp?B17506578.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
6

Li, Kai, i 李凯. "Photoluminescent organoplatinum (II) complexes containing N-heterocyclic carbene (NHC) ligands". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hub.hku.hk/bib/B50533915.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
Streszczenie:
The syntheses, structures, photophysical properties and applications of three types of photoluminescent organoplatinum(II) complexes containing N-heterocyclic carbene (NHC) ligands are described. The tetradentate dianionic bis(phenolate-NHC) type ligands provide a superior scaffold for constructing thermally stable and efficient deep-blue phosphorescent Pt(II) complexes with λmax of ~440-460 nm and solid-state emission quantum yields of ~30%. Highly efficient blue OLEDs with CIEx, y of (0.19, 0.21) were fabricated based on these emitters with maximum brightness, peak current efficiency and power efficiency of ~9500 cd m^(-2), 24 cd A^(-1) and 17 lm W^(-1), respectively. Structural modification by extending the π-conjugation of the tetradentate bis(phenolate-NHC) ligand leads to strongly phosphorescent platinum(II) complexes with long-lived emissive electronic states that can be used as a luminescent sensor for oxygen. DFT/TDDFT calculations and time-resolved spectroscopic characterizations were performed to gain insight into the structure-photophysics correlation. The N-heterocyclic carbene (NHC) ligand was incorporated into Pt(II) complexes containing tridentate deprotonated 1,3-bis(2-pyridyl)benzene (N^C^N) type ligand. In addition to the [(N^C^N)Pt(NHC)]PF6 type complexes with (N^C^N) in η3-tridentate coordination mode, Pt(II) complexes with η2-bidentate (N^CN) ligands, namely [(N^CN)Pt(NHC)2]PF6, have been isolated and structurally characterized. The highly phosphorescent [(N^C^N)Pt(NHC)]PF6 complexes were used for solution-processed green OLEDs fabrication. The peak current efficiency of 12.5 cd A^(-1) and maximum brightness higher than 2000 cd m^(-2) were achieved. The presence of the pendent pyridyl motif causes quenching of emission of the [(N^CN)Pt(NHC)2]PF6 complexes in solution at room temperature. Turning on solid-state emission of [(N^CN)Pt(nBu2Im)2]PF6 in the presence of an acidic vapor revealed its potential as a luminescent chemosensor. A class of dicationic platinum(II) terpyridyl complexes containing NHC ligand, namely [Pt(tpy)(NHC)](PF6)2, has been synthesized and structurally characterized. Even in the presence of the strong σ-donating NHC ligand, these complexes are non- or weakly emissive in solution at room temperature. However, this class of complexes displays intense emissions in solid state (298 K and 77 K), in glassy solution (77 K butyronitrile) and in PMMA (2 wt.%, 298 K). The ligand (terpyridine) displacement reaction arising from CN attack onto the Pt(II) center has been observed for [Pt(tpy)(nBu2Im)](PF6)2 leading to its application as a chemodosimeter for selective cyanide sensing in aqueous solution.
published_or_final_version
Chemistry
Doctoral
Doctor of Philosophy
7

Basu, Sayanti. "Synthesis and catalytic applications of new acceptor platinum alkyl cations". Laramie, Wyo. : University of Wyoming, 2009. http://proquest.umi.com/pqdweb?did=1939365871&sid=1&Fmt=2&clientId=18949&RQT=309&VName=PQD.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
8

Lai, Siu-wai. "Luminescent organoplatinum chemistry : photophysical and supramolecular properties of metallacyclic and polypyridine platinum(II) complexes /". Hong Kong : University of Hong Kong, 1999. http://sunzi.lib.hku.hk/hkuto/record.jsp?B20792943.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
9

Crisp, Michael G. "Organoplatinum(II) complexes with hydrogen-bonding functionality and their potential use as molecular receptors for adenine : a thesis submitted for the degree of Master of Science". Title page, abstract and contents only, 2002. http://web4.library.adelaide.edu.au/theses/09SM/09smc932.pdf.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
Streszczenie:
Errata pasted onto front end-paper. Includes bibliographical references (leaves 82-86). Describes the preparation and characterisation of a novel series of organoplatinum(II) complexes with hydrogen-bonding functionality.
10

Hung, Faan-fung, i 孔繁峰. "Luminescent platinum(II), palladium(II) and gold(III) complexes containing isocyanide, alkynyl and N-heterocyclic carbene ligands : synthesis, photophysical properties and material applications". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206318.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
11

Lai, Siu-wai, i 黎小慧. "Luminescent organoplatinum chemistry: photophysical and supramolecular properties of metallacyclic andpolypyridine platinum(II) complexes". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1999. http://hub.hku.hk/bib/B31238737.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
12

Zou, Taotao, i 邹滔滔. "Anti-cancer N-heterocyclic carbene complexes of gold(III), gold(I) and platinum(II) : thiol "switch-on" fluorescent probes, thioredoxin reductase inhibitors and endoplasmic reticulum targeting agents". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2015. http://hdl.handle.net/10722/208614.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
13

Yachnin, Jeffrey R. "Chemical, pharmacokinetic and biological aspects of platinum-based drugs /". Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-221-7/.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
14

Muro, Maria L. "Platinum (II) terpyridyls excited state engineering and solid-state vapochromic/vapoluminescent materials /". Bowling Green, Ohio : Bowling Green State University, 2009. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=bgsu1242057662.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
15

Nesbitt, Elizabeth. "Synthesis of a Novel Organoplatinum (II) Compound". Scholarship @ Claremont, 2015. http://scholarship.claremont.edu/scripps_theses/572.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
Streszczenie:
Preliminary NMR data indicate that a new platinum compound, assigned (TpyO)PtMe (TpyO = 2,6-bis-(2’pyridyl)-4-pyridonate), can be synthesized by the addition of impure trans-(DMSO)2PtMeCl to impure 2,6-bis(2’-pyridyl)-4-hydroxypyridine (TpyOH) in the presence of NEt3 in about 10% yield. It is likely that the yield could be increased by using purified TpyOH and (DMSO)2PtMeCl. The metalation step of the synthesis was also attempted using (COD)PtMeCl but was unsuccessful with either Na2CO3 or NEt3 as bases, most likely due to the chelate effect of the bidentate COD. Future work with (TpyO)PtMe will include the addition of H+/D+ to generate the platinum (IV) complex, [(TpyO)Pt(Me)(H)]+, and/or the σ-complex [(TpyO)Pt(Me-H)]+ in order to examine the kinetic, isotope, and thermodynamic effects of the resulting reductive elimination reaction.
16

Hong, Jin. "The synthesis and chemistry of platinum (II) hydroxo and hydroxycarbonyl complexes containing tertiary phosphine ligands". Phd thesis, 1990. http://hdl.handle.net/1885/140053.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
17

Van, Zyl Werner Ewald. "Sintese van goud(I)- en platinum (II) karbeenkomplekse". Thesis, 2014. http://hdl.handle.net/10210/10165.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
18

Richmond, Matthew Kevin. "Synthesis and reactivity of organoplatinum(II) hydroxo complexes". Phd thesis, 1999. http://hdl.handle.net/1885/147318.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
19

"Novel TCM-Platinum compounds: biological activity, cross-resistance and toxicity". 2001. http://library.cuhk.edu.hk/record=b6073360.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
Streszczenie:
To Kin Wah.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2001.
Includes bibliographical references (p. 293-345).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Mode of access: World Wide Web.
Abstracts in English and Chinese.
20

Patel, Jim. "Intramolecular coordination systems at platinum and palladium". Thesis, 2000. https://eprints.utas.edu.au/21151/1/whole_PatelJim2001_thesis.pdf.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
Streszczenie:
This thesis describes studies into the synthesis, characterisation and reactivity of organometallic complexes of the nickel triad elements containing intramolecular coordination systems based on N-heterocyclic donor groups. Oxidative addition of the bromoarene 2,6-bis{(3,5-dimethylpyrazol-1 yl)methyl}bromobenzene to [PtMez(SEt)2 ]2 gives the platinum(IV) complex PtBrMe2{2,6 (3,5-Me2pzCH2)2C6H3} in which the NCN ligand coordinates in a facial manner. The reagent reacts differently with [Pt(p-tolyl)z(SEt)2 ]2 to give the platinum(II) complex PtBr{2,6-(3,5 Me2pzCH2)2C6H3} and 4,4'-bitolyl. The method used to obtain the platinum(II) complex represents a new synthetic route to the platinum(II) NCN kernel and is shown to be applicable to other NCN ligand systems. Activation of both C(sp2)-H and C(sp3)-H bonds by palladium(II) acetate is used to generate aryl- and alkylpalladium(II) NCN complexes. Arylpalladium complexes are prepared with pyrazol-1-yl based donor groups and alkylpalladium complexes with pyrazol-1-yl, pyridin-2-yl and N-methylimidazol-2-yl donor groups. A hexametallic complex bearing six palladated NCN units at its periphery is obtained on palladation of the ligand hexakis{3,5 bis[(pyrazol-1-yl)methyl]phenyl} benzene. Oxidative addition of the bromoarene reagents 2,6-bis{ (pyrazol-1 yl)methyl} bromobenzene and 2,6-bis{ (3,5-dimethylpyrazol-1-yl)methyl} bromobenzene to the nickel(O) reagents affords nickel(II) NCN complexes. Cationic platinum, palladium and nickel NCN aqua complexes of the type [M(OH2){2,6 (3,5-Me2pzCH2)2C6H3} ][BF4], are found to catalyse the Michael addition of α-cyano carboxylates to methyl vinyl ketone. The palladium and nickel complexes are found to be more active catalysts than the platinum complex. Platinum(IV) and palladium(IV) complexes containing CN intramolecular coordination systems have been prepared. Ionic complexes of the type [PdR1R2{(pz)2BH2} ]K {(R1, R2) = (Me, Me), (Me, Ph), (Me, p-tolyl), (CH2CMe3, p-tolyl)} react with 8-(bromomethyl)quinoline to give the first isolable palladium(IV) complexes containing an intramolecular coordination system, Pd(CH2C9H6N-C,N)R1Rz{(pz)2BH2}. Structural studies of the complexes Pd(CH2C9H6N-C,N)Me2{(pz)2BH2} and Pd(CH2C9H6N-C,N)MePh{(pz)2BH2} reveal C-N intramolecular coordination of the 8-methylquinolinyl groups and include the first structural analysis of an arylpalladium(IV) complex. The palladium(IV) complexes show high thermal stability in solution but decompose in refluxing acetone by reductive elimination, with low selectivity in C-C coupling. The platinum complex Pt(CH2C9H6N-C,N)Me2{(pz)2BH2} has been prepared and found to be isostructural with Pd(CH2C9H6N-C,N)Me2{(pz)2BH2}, with the M-N bonds significantly longer for the palladium complex but the M-C bonds slightly shorter. Complexes containing bis(pyrazol-1-yl)borate in the absence of an intramolecular coordination system have also been studied, and include the structural characterisation of PtMe3 { (pz)2BH2} (py) and the detection of PdMe3 { (pz)2BH2} (PMePh2), the first example of a neutral palladium(IV) complex containing a phosphorus donor ligand.
21

Honeyman, RT. "Platinum-carbon bond formation by cyclometallation and oxidative addition reactivity of organoplatinum compounds". Thesis, 1988. https://eprints.utas.edu.au/20253/7/whole_HoneymanRonaldThomas1989.pdf.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
Streszczenie:
The work described in this thesis stems from the observation that a pyrazolyl group in Me2Pt(HCpz3) umdergoes a Cyclometallation reaction when heated in neat pyridine, giving rise to a NC- coordination mode, which is uncommon for flexible carbon bridged maltidentate ligands.... The chemistry of this novel cyclometallation system has been explored, together with related polydentate ligand systems and the oxidative addition reactivity of platinum(II) complexes, in order to extend our knowledge of reactivity of platinum(II) toward formation of organoplatinum(II) and platinum(IV) complexes with new structural features. A range of polydentate pyrazolyl ligands were chosen, or designed and synthesized, according to their ability to possibly undergo cyclometallation reactions.
22

"Structural factors that govern the synthesis efficiency of organoplatinum poly(dendrimer)s". Thesis, 2010. http://library.cuhk.edu.hk/record=b6074838.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
Streszczenie:
Chapter 1 gives a brief introduction about dendrimers, their synthesis, characterization methods and applications. Chapter 2 summarizes the current research progress on the various dendritic nanostructures, namely, dendronized polymers, dendrimer-linear polymer hybrids, poly(dendrimer)s and poly(dendrimer) networks. In Chapter 3, we reported the detailed synthesis of the two series of dendritic macromonomers (S-Gn and L-Gn, n = 1--3) with different branch lengths (C-O for S-Gn and C--C--C--O for L-Gn) and hence varying structural flexibilities. The structures of these dendritic compounds were characterized by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography (GPC), mass spectrometry (MS) and elemental analysis. The polymerization reactions with trans -Pt-linker 65 was firstly conducted to obtain organoplatinum poly(dendrimer)s Pt-S/L-Gn 144-149. It was found that the structurally more rigid dendritic mamcromonomers (S-Gn series) have a higher degree of polymerization (DP) than the structurally more flexible one (L-Gn series) of the same generation. This was attributed to the formation of cyclic oligomers in the latter series. In Chapter 4, we investigated the polymerization behavior of the two series of dendritic macromonomers towards two other Pt-linkers of different geometry, namely, cis-Pt-linker 152 and long-trans-Pt-linker 156 to obtain poly(dendrimer)s cis-Pt-S/L-Gn 157-162 and long-trans-Pt-S/L-Gn 163-168 respectively. It was revealed that only oligomers and/or cyclic oligomers were formed in both S-Gn and L-Gn series in the former case. In contrast, poly(dendrimer)s long-trans-Pt-S/L-Gn 163-168 were obtained in high DP values and the formation of oligomers and/or cyclic oligomers was greatly suppressed. A model was proposed to account for the different polymerization outcomes based on the different steric and structural environment of the two reacting partners. A conclusion of this work and an outlook of the project were given in Chapter 5.
This thesis described the research work on the synthesis of poly(dendrimer)s using an outer-sphere--outer-sphere connection strategy. Two G1--G3 series of dendritic macromonomers having short branches ( 73-75) and long branches (76-78) containing two surfaces (functionalized acetylene surface groups) were prepared in high purity and copolymerized with three different type of platinum linkers 65, 152 and 156 to form organoplatinum poly(dendrimer)s. The structural effects of the dendritic macromonomers and platinum tinkers on the polymerization efficiency were investigated.
Cheung, Siu Yin.
"December 2009."
Adviser: Hak-Fun Chow.
Source: Dissertation Abstracts International, Volume: 72-01, Section: B, page: .
Thesis (Ph.D.)--Chinese University of Hong Kong, 2010.
Includes bibliographical references (leaves 146-159).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.
23

Mitchell, Kathryn Allison. "Synthesis, characterization, and reactivity of platinum cysteinato and related thiolato complexes : model studies of the reversal of cisplatin nephrotoxicity". Thesis, 1995. http://hdl.handle.net/10125/9526.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
24

"First synthesis and characterization of organoplatinum dendritic necklaces and dendritic networks using an outer sphere-outer sphere connection strategy". 2003. http://library.cuhk.edu.hk/record=b6073556.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
Streszczenie:
by Leung Cham-fai.
"July, 2003."
Thesis (Ph.D.)--Chinese University of Hong Kong, 2003.
Includes bibliographical references (p. 135-150) and index.
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Mode of access: World Wide Web.
Abstracts in English and Chinese.
25

Ariaratnam, Vimala. "Asymmetric synthesis of chiral glycerol derivatives with use of platinum (II) phosphine complexes". Phd thesis, 1990. http://hdl.handle.net/1885/138986.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
26

"Drug action mechanism of platinum antitumour compounds: a DFT study". 2004. http://library.cuhk.edu.hk/record=b6073739.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
Streszczenie:
Pang Siu Kwong.
"August 2004."
Thesis (Ph.D.)--Chinese University of Hong Kong, 2004.
Includes bibliographical references (p. 181-191)
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Mode of access: World Wide Web.
Abstracts in English and Chinese.
27

Beek, Johannus Antonius Maria van. "Synthesis and reactivity of cyclometalated Ni(II), Pd(II) and Pt(II) complexes". 1990. http://catalog.hathitrust.org/api/volumes/oclc/25889954.html.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
28

"Mechanistic and pharmacokinetic studies of novel TCM-Platinum compounds". 2002. http://library.cuhk.edu.hk/record=b6073420.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
Streszczenie:
Wang Xin Ning.
"May 2002."
Thesis (Ph.D.)--Chinese University of Hong Kong, 2002.
Includes bibliographical references (p. 201-236).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Mode of access: World Wide Web.
Abstracts in English and Chinese.
29

Wang, Shaoyu. "Structure-activity screening of platinum intercalators and molecular mechanisms for the cytotoxicity of 56MESS - [Pt(5,6-Dimethyl-Phen)(1S,2S-DACH)]²⁺". Thesis, 2011. http://handle.uws.edu.au:8081/1959.7/506756.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
Streszczenie:
Efficacy of existing clinical anticancer drugs including cisplatin and its analogues is greatly limited by drug resistance and side effects. Anticancer compounds with novel structures and different mechanisms of action have been sought to expand anticancer activity and to minimise these limitations. First part of this project evaluated the structure-activity relationships for a class of novel platinum metallointercalators using cytotoxicity screening against cancer cell lines, and subsequently identified lead compounds. Second part elucidated the biological mechanisms underlying the cytotoxic action of a lead compound with a genome-wide gene expression profiling technology (or transcriptomics) using a eukaryotic model organism yeast Saccharomyces cerevisiae. These analyses identified the disruption of iron and copper metabolism as the major molecular mechanism of cytotoxic action of the lead compound. The novel platinum(II) metallointercalators studied are of the type of [Pt(IL)(AL)]2+, where IL is the intercalating ligand, such as 1,10-phenanthroline (phen), and AL is the ancillary ligand, either chiral 1,2-diaminocyclohexane (S,S-DACH, R,R-DACH), or achiral 1,2-diaminoethylene (EN). Nineteen (19) platinum metallointercalators, eleven (11) cucurbit[n]ural encapsulated forms of these complexes and three (3) non-platinum metal helicates were screened against cisplatin-sensitive (L1210) and resistant (L1210cisR) murine leukaemia cell lines using a standard methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. These metal complexes are water-soluble. They exhibited a wide range of cytotoxicities. The complex - [Pt(5,6-dimethyl-1,10-phen)(1S,2S-DACH)]2+ (56MESS) was found to be 163-fold more active than cisplatin against the L1210cisR cell line whereas complexes such as [Pt(4-methyl-phen)(EN)]2+ (4MEEN) are inactive. Correlation analysis of the cytotoxicity data with structures revealed three major structure-activity relationships. Chirality of the DACH ligand, the position and electronegativity of functional groups substituted in the intercalating ligand and type of ancillary ligands (i.e DACH or EN) profoundly influenced the cytotoxicity of these complexes. Encapsulation of metal complexes by different sized curcurbit[n]urals led to varied cytotoxicities. Analysis of these data resulted in the identification of three lead complexes including 56MESS, which has excellent activity in L1210 as well as in L1210cisR cell lines. To understand the biological mechanisms underlying the cytotoxicity of the lead complex 56MESS, genes and pathways in response to 56MESS treatment, in parallel to cisplatin treatment, were investigated using transcriptomics in yeast Saccharomyces cerevisiae. Ninety-three (93) genes were revealed to be important for the cytotoxicity of 56MESS as these genes altered their expressions in response to 56MESS challenge. Bioinformatics analysis of these genes showed that defective iron and copper metabolisms are implicated for the cytotoxic action of this compound. The suppression of biosynthesis of sulphur-containing amino acids and arginine and function of mitochondria could also play a role in the cytotoxicity of 56MESS. In comparison, one hundred and sixty-five (165) genes altered their expressions in response to cisplatin treatment. The genes involved in sulphur uptake and its assimilation and response to DNA damage were up-regulated while the genes involved in de novo purine biosynthesis and one carbon metabolism were suppressed by cisplatin. The differences in the major pathways in response to 56MESS and cisplatin suggest that these two platinum agents have different molecular mechanisms for their cytotoxicity. Cellular assays and gene deletion mutant screenings validated these transcriptomic findings. The results from inductively coupled plasma optical emission spectrometry (ICP-OES) revealed that 56MESS treatment reduced concentrations of the intracellular iron and copper, and increased that of manganese. Analysis of viability phenotypes of deletion mutants of the key genes including FTR1 in the iron and copper metabolisms further supported their involvement in the cytotoxicity of 56MESS. The data therefore suggested that iron and copper transporters were the molecular targets of 56MESS. Further biochemical and mutant analyses showed that glutathione, oxidative stress and mitochondria were important in 56MESS' cytotoxicity. 56MESS treatment arrested cells in G1 phase of the cell cycle. The cytotoxicity data, the structure-activity relationships and the elucidated molecular mechanisms of the most active platinum metallointercalator 56MESS suggested that the platinum metallointercalators of the type [Pt(IL)(AL)]2+ have potential as anticancer agents. The findings reported in this thesis can be used for further development of these complexes.

Do bibliografii