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Understanding Human Erythrocyte Glucose Transporter (GLUT1) Mediated Glucose Transport Phenomena Through Structural AnalysisLloyd, Kenneth P. 26 February 2018 (has links)
GLUT1-mediated, facilitated sugar transport is proposed to be an example of transport by a carrier that alternately presents exofacial (e2) and endofacial (e1) substrate binding sites, commonly referred to as the alternating access carrier model. This hypothesis is incompatible with observations of co-existent exo- and endofacial ligand binding sites, transport allostery, and e1 ligand (e.g. cytochalasin B) induced GLUT1 sugar occlusion. The fixed-site carrier model proposes co-existent, interacting e2 and e1 ligand binding sites but involves sugar translocation by geminate exchange through internal cavities. Demonstrations of membrane-resident dimeric and tetrameric GLUT1 and of e2, e1 and occluded GLUT conformations in GLUT crystals of monodisperse, detergent-solubilized proteins suggest a third model. Here, GLUT1 is an alternating access carrier but the transporter complex is a dimer of GLUT1 dimers, in which subunit interactions produce two e2 and two e1 conformers at any instant. The crystallographic structures in different conformations can be utilized to further understand the transport cycle, ligand binding behavior and complex kinetics observed in GLUT1. Specifically, the GLUT1 crystal structure and homology models based upon related major facilitator superfamily proteins were used in this study, to understand inhibitor binding, ligand binding induced GLUT1 transport allostery and the existence of helix packing/oligomerization motifs and glycine induced flexibility. These studies suggest that GLUT1 functions as an oligomeric allosteric carrier where cis-allostery is an intramolecular behavior and trans-allostery is an intermolecular behavior. Additionally, mutations of a dynamic glycine affect the turnover of the transporter while mutations to helix packing motifs affect affinity.
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Tunable Twisting Motion of Organic Linkers via Concentration and Hydrogen-bond FormationAlturki, Abdullah 01 1900 (has links)
Benzothiazole dibenzoic acid derivative (BTDB) is well-known organic linkers utilized for the syntheses of various metal organic frameworks, and demonstrates interesting photophysical properties upon concentration variations in solution. The presence of two carboxylic acid functional groups at each side of the rod-like molecule, facilitates dimerization and oligomerization equilibria. Interestingly, dimers and oligomers have completely different emission behaviors from the monomer of the same species. At a low range of concentration, 0.1 – 64 μM, dimerization process is dominant, and that the equilibrium constant of dimer formation found to be 18,000 M-1. On the other hand, in the 64 – 1000 μM concentration range, oligomerization takes over, and that it results in the formation of a small linear chain of 8 molecules, or 4 dimers, with a high equilibrium constant of 1.2 × 1013 M-3. Various experimental measurements and theoretical calculations have suggested hydrogen-bond formation is the main driving force for the dimerization and oligomerization in the nano- and micro- molar regime, and that structure rigidity of a species is a key factor in controlling its photophysical properties, such as emission quantum yield and excited state lifetime.
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Biophysical and Structural Characterization of Shigella ATPase Spa47 Oligomerization Provides Insight Into Type Three Secretion System Activation and VirulenceBurgess, Jamie L. 01 August 2019 (has links)
Several bacterial pathogens including Shigella (shigellosis), Escherichia coli (urinary tract infections), Pseudomonas (lung infections), Salmonella (food poisoning), and Yersinia (plague) critically rely on a complex type three secretion system (T3SS) for infection. With the rise in multi-antibiotic resistant strains of several of these pathogens, we turn to the T3SS as a promising target for the development of novel therapeutics. The Dickenson lab at Utah State University has been the first to identify and characterize the ATPase Spa47, the energy source of the Shigella infection system. We show that Spa47 is necessary for proper T3SS formation and function, being ultimately responsible for overall Shigella virulence. We find that proper ATPase function and in turn T3SS apparatus formation can be affected by something as simple as a single mutation to the removal of a non-catalytic domain. The insights gained from this work expands our understanding of the powerhouse that fuels these infection systems and brings us a step closer to developing novel therapeutics to combat infection.
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Biophysical analysis of MyD88 and related proteins / MyD88及び関連タンパク質の分子機構解析Uno, Masatoshi 25 March 2019 (has links)
付記する学位プログラム名: 充実した健康長寿社会を築く総合医療開発リーダー育成プログラム / 京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第21790号 / 工博第4607号 / 新制||工||1718(附属図書館) / 京都大学大学院工学研究科分子工学専攻 / (主査)教授 白川 昌宏, 教授 梶 弘典, 教授 森 泰生 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM
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Towards Selective Ethylene TetramerizationShaikh, Yacoob 21 August 2012 (has links)
There is an increasing trend towards advancing the understanding and development of ethylene oligomerization catalysts, both in academia and industry. The metal of choice in this chemistry is invariably chromium, which has shown great versatility in selective trimerization/tetramerization, non-selective oligomerization and polymerization of ethylene. While much success has been achieved in ethylene trimerization, the same con not be said about tetramerization catalysis. Aminophosphine based ligands have demonstrated their ability towards selective 1-octene production, however, the popular PNP catalyst is able to achieve only 70% selectivity. In order to explore the possibility of developing and enhancing the selectivity of chromium based ethylene tetramerization catalyst, this thesis work was undertaken. The ligand systems we chose for our work were bidentate aminophosphine based (PN(CH2)nNP), which has yielded interesting selective oligomerization. Subtle modifications were found to result in drastic changes in selectivity, from tetramerization (PN(CH2)3NP) to trimerization (PN(CH2)2NP). We managed to successfully develop the first truly selective (over 90%) 1-octene catalyst with polymer-free behavior. Further modifications on the ligand framework, where one atom of Si was used to link the two NP units, resulted in non-selective oligomerization, in which case we determined that the oxidation-state of chromium is a key player. We explored other modifications on our selective ligands in which one of the arms on the bidentate ligand was replaced with a base-donor amine, phosphine or pyridine, and resulted in interesting selectivity changes. The final modification that we tested was a novel N(CH2)2P ligand and found it to be a highly active, non-selective oligomerization catalyst.
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Towards Selective Ethylene TetramerizationShaikh, Yacoob 21 August 2012 (has links)
There is an increasing trend towards advancing the understanding and development of ethylene oligomerization catalysts, both in academia and industry. The metal of choice in this chemistry is invariably chromium, which has shown great versatility in selective trimerization/tetramerization, non-selective oligomerization and polymerization of ethylene. While much success has been achieved in ethylene trimerization, the same con not be said about tetramerization catalysis. Aminophosphine based ligands have demonstrated their ability towards selective 1-octene production, however, the popular PNP catalyst is able to achieve only 70% selectivity. In order to explore the possibility of developing and enhancing the selectivity of chromium based ethylene tetramerization catalyst, this thesis work was undertaken. The ligand systems we chose for our work were bidentate aminophosphine based (PN(CH2)nNP), which has yielded interesting selective oligomerization. Subtle modifications were found to result in drastic changes in selectivity, from tetramerization (PN(CH2)3NP) to trimerization (PN(CH2)2NP). We managed to successfully develop the first truly selective (over 90%) 1-octene catalyst with polymer-free behavior. Further modifications on the ligand framework, where one atom of Si was used to link the two NP units, resulted in non-selective oligomerization, in which case we determined that the oxidation-state of chromium is a key player. We explored other modifications on our selective ligands in which one of the arms on the bidentate ligand was replaced with a base-donor amine, phosphine or pyridine, and resulted in interesting selectivity changes. The final modification that we tested was a novel N(CH2)2P ligand and found it to be a highly active, non-selective oligomerization catalyst.
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Towards Selective Ethylene TetramerizationShaikh, Yacoob January 2012 (has links)
There is an increasing trend towards advancing the understanding and development of ethylene oligomerization catalysts, both in academia and industry. The metal of choice in this chemistry is invariably chromium, which has shown great versatility in selective trimerization/tetramerization, non-selective oligomerization and polymerization of ethylene. While much success has been achieved in ethylene trimerization, the same con not be said about tetramerization catalysis. Aminophosphine based ligands have demonstrated their ability towards selective 1-octene production, however, the popular PNP catalyst is able to achieve only 70% selectivity. In order to explore the possibility of developing and enhancing the selectivity of chromium based ethylene tetramerization catalyst, this thesis work was undertaken. The ligand systems we chose for our work were bidentate aminophosphine based (PN(CH2)nNP), which has yielded interesting selective oligomerization. Subtle modifications were found to result in drastic changes in selectivity, from tetramerization (PN(CH2)3NP) to trimerization (PN(CH2)2NP). We managed to successfully develop the first truly selective (over 90%) 1-octene catalyst with polymer-free behavior. Further modifications on the ligand framework, where one atom of Si was used to link the two NP units, resulted in non-selective oligomerization, in which case we determined that the oxidation-state of chromium is a key player. We explored other modifications on our selective ligands in which one of the arms on the bidentate ligand was replaced with a base-donor amine, phosphine or pyridine, and resulted in interesting selectivity changes. The final modification that we tested was a novel N(CH2)2P ligand and found it to be a highly active, non-selective oligomerization catalyst.
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The use of chromium/bis(diphenylphosphino)amine catalysts in tandem ethylene copolymerization processesDu Toit, Aletta 03 1900 (has links)
Thesis (PhD)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: The possibility of utilizing the chromium/bis(diphenylphosphino)amine (PNP) type of
catalysts in ethylene polymerization processes was investigated. These processes
include the production of linear low density polyethylene (LLDPE), the production of
polyethylene waxes and the synthesis of special comonomers for ethylene
copolymerization.
The chromium/Ph2PN{CH(CH3)2}PPh2 tetramerization system was used in
combination with a polymerization catalyst to yield ethylene copolymers with
controlled branching. Copolymers with bimodal chemical composition distributions
were obtained in these tandem reactions. This chromium/PNP-type tetramerization
catalyst and metallocene polymerization catalysts are not completely compatible in
tandem catalytic systems due to different optimum temperatures for their effective
functioning. The oligomerization to polymerization catalyst ratios, the catalyst to
cocatalyst ratios and the temperature profile are all factors influencing the amount of
-olefins formed and therefore the type of copolymer produced. The activity of the
polymerization catalyst decreases in the presence of the oligomerization catalyst,
indicating that the two catalysts interfere chemically. The main difference between
copolymers produced in conventional or tandem fashion is the presence of a small
amount of low molecular weight material produced by the oligomerization catalyst
and also the presence of a highly crystalline component. The latter component
results from the initial low concentration of a-olefins in the first conversion, but such a
component is also independently produced by the oligomerization catalyst.
LLDPE with butyl branches is obtained when a selective trimerization catalyst is used
in combination with a polymerization catalyst. The chromium/(o-OMeC6H4)2
PN(CH3)P(o-OMeC6H4)2 trimerization system is more suitable than the
chromium/Ph2PN{CH(CH3)2}PPh2 tetramerization system for use in tandem reactions
with a metallocene catalyst due to its high activity and selectivity at higher
temperatures. The chemical composition distribution varies with an increase in
reaction time due to the increasing amount of 1-hexene produced. Comparison of
CRYSTAF traces of tandem copolymers with conventional copolymers show that the
tandem copolymers have a broader chemical composition distribution. Addition of 1-
hexene during the course of a conventional copolymerization reaction produces
copolymers with similar chemical composition distributions to that of the tandem copolymers. Later addition of the polymerization catalyst to the oligomerization
reaction mixture results in copolymers with higher comonomer content, similar to
conventional copolymers.
Chromium/(o-EtC6H4)2PN(CH3)P(o-EtC6H4)2 is not suitable for LLDPE production in
tandem reactions, since it is selective to higher oligomers or polyethylene waxes at
higher temperatures. Variation of the MAO cocatalyst and hydrogen concentrations
significantly influences the yield, viscosity and crystallization behaviour of the waxlike
products. Low MAO concentrations resulted in multiple melting peaks, while
higher concentrations display single melting peaks and lower viscosity values.
Ethylene co-oligomerization reactions with styrene or p-methylstyrene using the
chromium/PNP-type oligomerization technology produce various phenyl-hexene and
phenyl-octene isomers either through cotrimerization or cotetramerization. The
known ethylene trimerization catalysts show cotrimerization behaviour, while the
catalysts with known selectivity for ethylene tetramerization also yield
cotetramerization products. Chromium complexes that contain the more bulky
ligands display lower selectivity towards co-oligomerization and greater preference
for ethylene homotrimerization.
These co-oligomerization products can be incorporated into a polyethylene chain by
copolymerization in a simultaneous or sequential tandem reaction. The combined
co-oligomerization-polymerization reactions yield copolymers with lower crystallinity
than obtained from the conventional ethylene-styrene copolymerization reaction due
to higher comonomer incorporation. The polymer yields are higher in the cooligomerization-
copolymerization reactions. The ability of the different cooligomerization
products to incorporate into the polyethylene chain was established:
unreacted styrene and the more bulky isomers, 3-phenyl-1-hexene and 3-phenyl-1-
octene, are not incorporated readily, while branches resulting from 4-phenyl-1-
hexene, 4-phenyl-1-octene, 5-phenyl-1-octene and 6-phenyl-1-octene are detected in
the NMR spectrum. / AFRIKAANSE OPSOMMING: Die moontlikheid om die chroom/bis-(difenielfosfino)amien (PNP) tipe katalisatore in
etileen-polimerisasie reaksies te gebruik is ondersoek. Hierdie prosesse sluit die
produksie van lineêre lae digtheid poliëtileen (LLDPE), die produksie van
poliëtileenwasse en die sintese van spesiale komonomere vir etileenkopolimerisasie
in.
Die chroom/Ph2PN{CH(CH3)2}PPh2 tetramerisasie-sisteem is gebruik in kombinasie
met ¢n polimerisasiekatalisator om etileenkopolimere met gekontroleerde vertakkings
te vorm. Kopolimere met ‘n bimodale chemiese samestellingsverspreiding word
verkry in hierdie tandemreaksies. Hierdie chroom/PNP-tipe tetramerisasiekatalisator
en die metalloseenkatalisators is nie heeltemal verenigbaar in die tandemsisteem nie
weens verskille in hul optimum reaksietemperature vir effektiewe funksionering. Die
oligomerisasie tot polimerisasiekatalisatorverhouding, die katalisator tot
kokatalisatorverhouding en die temperatuurprofiel is almal faktore wat die gevormde
hoeveelheid -olefiene beinvloed, en dus die tipe kopolimeer wat gevorm word. Die
aktiwiteid van die polimerisasiekatalisator verminder in die teenwoordigheid van die
oligomerisasiekatalisator, wat aandui dat die twee katalisatore chemies met mekaar
inmeng. Die duidelikste verskil tussen die kopolimere wat geproduseer word op die
konvensionele of die tandem manier is die teenwoordigheid van ‘n klein hoeveelheid
lae molekulere massa materiaal wat gevorm word deur die oligomerisasiekatalisator,
asook ‘n komponent met baie hoë kristalliniteit. Die laasgenoemde komponent
ontstaan weens die aanvanklike lae konsentrasie van die a-olefiene in die eerste
omsetting, maar so ‘n komponent word ook onafhanklik gevorm deur die
oligomerisasiekatalisator.
LLDPE met butiel-vertakkings word verkry wanneer ‘n selektiewe
trimerisasiekatalisator in kombinasie met ‘n polimerisasiekatalisator gebruik word.
Die chroom/(o-OMeC6H4)2PN(CH3)P(o-OMeC6H4)2 trimerisasiesisteem is meer
geskik as die chroom/Ph2PN{CH(CH3)2}PPh2 tetramerisasiesisteem vir gebruik in
tandem met ‘n metalloseenkatalisator weens die katalisator se hoë aktiwiteit en
selektiwiteid vir 1-hekseen by hoër reaksietemperature. Die chemiese
samestellingsverspreiding verander soos die reaksietyd toeneem weens die
toenemende hoeveelheid 1-hekseen wat gevorm word. Vergelyking van die
CRYSTAF-diagram van die tandemkopolimere met konvensionele kopolimere toon dat die tandemkopolimere ‘n wyer chemiese samestellingsverspreiding het.
Geleidelike byvoeging van 1-hekseen gedurende die loop van ‘n konvensionele
reaksie, vorm kopolimere met ‘n soortgelyke chemiese samestelingsverspreiding as
die tandemkopolimere. Latere byvoeging van die polimerisasiekatalisator lei tot die
vorming van kopolimere met ‘n hoër komonomeerinhoud, soortgelyk aan die
konvensionele kopolimere.
Chroom/(o-EtPC6H4)2PN(CH3)P(o-EtC6H4)2 is nie geskik om LLDPE in
tandemreaksies te vorm nie, aangesien dit selektief is vir hoër oligomere of
poliëtileenwasse by hoër reaksietemperature. Variasie van die MAO-kokatalisator en
die waterstofkonsentrasies beinvloed die hoeveelheid produk wat gevorm word,
asook die viskositeit en kristallisasiegedrag daarvan. Lae MAO konsentrasies lei tot
meer as een smeltpiek, terwyl hoër konsentraises ‘n enkelpiek vertoon. Die
viskositeit van die produkmengsel is ook laer.
Die gebruik van die chroom/PNP-tipe oligomerisasietegnologie in etileenkooligomerisasiereaksies
met stireen, lei tot die vorming van verskeie feniel-hekseenen
fieniel-okteenisomere deur of kotrimeriasie, of kotetramerisasie. Katilisatore met
bekende etileentrimerisasieligande vertoon kotrimerisasiegedrag terwyl die ligande
wat bekend is vir selektiwiteit in etileentetramerisasie, kotetramerisasieprodukte
vorm. Die chroomkomplekse met die meer bonkige ligande het laer selektiwiteit vir
ko-oligomerisasie en vertoon ‘n groter voorkeur vir etileenhomo-trimerisasie.
Die ko-oligomerisasieprodukte kan in ‘n poliëtileenketting ingebou word deur kopolimerisasie
in ‘n gelyktydige of opeenvolgende tandemreaksie. Die
gekombineerde ko-oligomerisasie-polimerisasiereaksie vorm kopolimere van ‘n laer
kristalliniteit as wat gevind word met die konvensionele etileen-stireen
kopolimerisasie reaksie weens hoer komonomeerinkorporasie. Meer polimeer word
gevorm in die ko-oligomerisasie-kopolimerisasie reaksie. Die vermoë van die
verskillende ko-oligomerisasieprodukte om in die poliëtileenketting ingesluit te word
is bepaal. Ongereageerde stireen en die meer bonkige isomere, 3-feniel-1-hekseen
en 3-feniel-1-okteen, word nie maklik ingevoeg nie. Vertakkings as gevolg van die
inkorporasie van 4-feniel-1-hekseen, 4-feniel-1-okteen, 5-feniel-1-okteen and 6-
feniel-1-okteen kan waargeneem word in die KMR spektrum.
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The preparation and characterization of multinuclear catalysts based on novel dendrimers : application in the oligomerization and polymerization of unsaturated hydrocarbonsMalgas-Enus, Rehana 03 1900 (has links)
Thesis (PhD)--University of Stellenbosch, 2011. / In this thesis we describe the application of novel salicylaldimine and iminopyridyl
nickel metallodendrimer complexes as catalysts in the transformation of á-olefins as well as
in the polymerization of norbornene.
New cyclic dendrimers based on cyclam as a core (L1-L8) were synthesized and
characterized via FTIR and NMR spectroscopy, mass spectrometry and microanalysis.
Subsequently the generation 1 cyclam-based dendrimers as well as the commercial
generation 1 to generation 3 DAB-PPI dendrimers were functionalized with salicylaldimine
and iminopyridyl moieties on the periphery to produce new ligands, DL1-DL10. These
modified dendritic ligands were subsequently complexed to Ni salts to obtain the
metallodendrimer complexes, C1-C8. The metallodendrimers were characterized by FTIR
spectroscopy, mass spectrometry, microanalysis, magnetic susceptibility measurements,
UV-Vis spectroscopy and thermal gravimetrical analysis (TGA).
The DAB G1-G3 salicylaldimine ligands (DL1-DL3) were subjected to
computational studies and the optimized structures were obtained by density functional
theory (DFT) calculations. The effect of the increase in dendrimer generation on the
structural arrangement of the dendrimer was also investigated. The following aspects were
probed using molecular modeling: a) the possible coordination site for the Ni to the first
generation dendrimer ligand, DL1, and b) the optimized structure of the first generation
salicylaldimine nickel complex, C1.
We subsequently evaluated catalysts, C1-C7, in the vinyl polymerization of
norbornene, using methylaluminoxane (MAO) as a co-catalyst. All the catalysts were found
to be active for norbornene polymerization with the weight of the polymers obtained ranging
from 5.12 x 105 - 11.17 x 106 g/mol. The DAB-based iminopyridyl catalysts (C4-C6)
exhibited higher activities than its analogous salicylaldimine catalysts (C1-C3) under the
same reaction conditions. Also, the cyclam-based salicylaldimine nickel catalyst (C7)
exhibited higher activities than the DAB-based salicylaldimine nickel catalyst, C1. A
negative dendritic effect was observed for the G1-G3 DAB salicylaldimine catalysts since the
optimum activity for the G3 catalyst, C3, was lower than that for the G2 catalyst, C2.
These nickel complexes were also evaluated as ethylene oligomerization catalysts and
were found to produce a range of ethylene oligomers (C4-C18) as well as some longer chained
oligomers, when employing EtAlCl2 as a co-catalyst. We observed however that the free
EtAlCl2 mediates the Friedel-Crafts alkylation of the solvent, toluene, in the presence of the
obtained ethylene oligomers to give uneven carbon number products, which are mixtures of
alkylated benzenes.
Our metallodendrimer catalysts also isomerized and in some cases dimerized
1-pentene. In both ethylene oligomerization and 1-pentene isomerization processes, the
salicylaldimine catalysts exhibited higher activity towards olefin transformation than the
iminopyridyl catalysts. The cyclam-cored dendrimer catalyst again showed the highest
activity. From the results obtained thus far it can be concluded that these nickel
metallodendrimers exhibit great potential as catalysts in the transformation of unsaturated
hydrocarbons.
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The Challenge of Selectivity in Ethylene Oligomerization: Ligand Design and Metal Valence StatesThapa, Indira 23 August 2012 (has links)
Catalytic ethylene oligomerization is a well understood industrially viable process. The large majority of scientific literature and patents concerning this process has been developed with the use of chromium catalysts. Commercial systems producing selective tri/tetramerization, non-selective oligomerization and polymerization are all based on this metal with the exception of a few systems based on other transition metals (Zr, Ti, Ni etc.). This versatility raises interesting questions about chromium’s unique behaviour. Essentially, selective or non-selective oligomerization and polymerization processes could be regarded as belonging to the same category of C-C bond forming reactions, though different mechanisms are involved. The first part of this thesis explores a variety of chromium complexes for ethylene oligomerization purposes. In order to gather further information about the unique behaviour of chromium, we have explored a variety of nitrogen and phosphorus containing ligands. We started with a simple bi-dentate anionic amidophosphine (NP) ligand and assessed the role of the ligand’s negative charge and number of donor atoms in determining the type of catalytic behaviour in relation to the metal oxidation state. This ligand proved capable of generating a series of chromium dimeric, tetrameric or polymeric and even heterobimetallic chromium-aluminate complexes in different valence states. This allowed us to isolate a “single component” self activating Cr(II) complex as well as a rare example of mixed valence Cr(I)/Cr(II) species. Additionally, each of these species acted as switchable catalyst depending on the type of co-catalyst
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