Soutenue par Siphesihle Robin NXELE Le 01-12-2021 Ecole PDF

Quelques Remarques : => Après la formation de la liaison les 2 électrons appartiennent à la fois aux 2 atomes. => On peut trouver des liaisons simples

CM2_Poly2_TP Géométrie des Molécules

CH7/CM2 – TP – Géométrie des Molécules. Géométrie des Molécules. Géométrie des Molécules – 1/2 (voir chapitre précédent – structure de l'atome).

Molecular science and two-dimensional materials: hybrid system for

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Molécules chirales à géométrie hélicoïdale: synthèse et modulation

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Interfacing responsive molecules with 2D semiconductors

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Interfaçage des molécules réactives avec des semi-conducteurs 2D

Diagramme de niveau d'énergie structure moléculaire et du dispositif. Chapter 7: Ternary-Responsive Field-Effect Transistors Based on Asymmetrically.

Étude de la structure des propriétés de surface et de la réactivité de

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Soutenue par Siphesihle Robin NXELE Le 01-12-2021 Ecole

?? ???? ????? ???? ?? Figure 1 : Structures des molécules de phtalocyanine utilisées ... prévu tous les GQDs ont montré des mobilités négatives (-7.5 x 10-4 cm2.

Pathologie inflammatoire: étude de la contribution des PAMP et DAMP

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µedications

èo the village that raised me and got me this farr to my parents zsrael and 'haron

0xeler and to the researchers that will come after me and

be inspired by this work, ÒHereÕs to the end of this chapter. To all the late nights, early mornings, learnings gained, and experiences shared. HereÕs to the hardships that became our teachers, to the heaviness that taught us how to rise again and to the people who would stop their world to sit and celebrate our presence. HereÕs to the times we chose feeling over disconnection, freedom over perfection, courage over whatÕs known and certain, and doing the work. HereÕs to releasing what wasnÕt ours to keep. HereÕs to holding our palms wide open to our blessings. And hereÕs to taking one step forward into the hope and possibil ity of tomorrow.Ó - Danielle Doby C ≡cknowledgements èo my supervisor and the powerhouse who made this Chy dream a reality for mer distinguished Professor Tebello

Nyokongr z cannot thank you enough Crof, z am

forever grateful, èhank you to yr Tethi qedioui as well as my supervisors at ;himie Caristechr Crof, -nne 'arenner yr Tanny dÕNrlyer yr 1aura èrapiellak-lfonso and my research group in Trance for hosting me and being a part of this Chy journey, èhank you to Crofessor Chilani 2ashazi and Crofessor /anice 1imson for helping me at the very beginning of this journey with bringing this project to life z also express my sincere gratitude to 2 is s xail ;obusr yr /onathan qrittonr Crofessor /ohn 2ack and 2r Trancis ;hindeka for their support and help during the course of this research, èhank you to yr yavid Nluwoler who mentored me at that start of this Chy journey, èhank you to my lab 'mm colleagues who have always been so helpful, - special thank you goes to 2r èendai ;honzir yr -llan 'anyangar 2iss àeitumetse

0khahler 2iss 'ivu

2apukata and 2r 0namdi 0wahara for being my support structure

in and out of this academic space, èhank you to my friends and family for your lover kindness and patience throughout this journey, e C e C -reface èhe need for lowkcostr efficient and simple diagnostic tools has led to more research going into this subjectr with the aim of making such medical devices more accessible where they are needed, èhis has led to more researchers developing point k of k care devi ces for this purpose worldwider by sensor fabrication, èhis thesis focuses on electrochemical sensor development for the early diagnosis of prostate cancer, zt is common knowledge that prostate cancer is one of the most prevalent carcinomas that have claim ed lives due to late diagnosis where even the most invasive treatments have failed, Tor this reasonr development of early detection devices that can even be used in the co mfo rt o f home is necessary and quite crucial,

Mlectrochemical sensors have gained muc

h attention due to their ease of fabricationr cost effectivenessr simplicityr ease of use and high efficiency, çsing nanocomposites as modifiers has also become popular as they provide greater stability and improve detection limits when used together with biomolecules, ïith that saidr the work reported herein has combined nanocomposites of graphene k based quantum dotsr gold nanoparticlesr phthalocyanines and an aptamer in order to fabricate aptasensors for the electrochemical detection of prostate cancer biomarker, èhe aptamer is specifically designed to bind to the biomarkerr and the nanocomposites are expected to enhance current output thus lowering detection limits a nd increasing stability and efficiency , àeproducible results are also expected, Crior to th e detection of the prostate cancer biomarkerr the quantum dotskphthalocyanine nanohybrids were used to detect 1 k cysteiner which is an amino acidr in order to verify the synergistic effects as electrode modifiers that lead to the enhancement of current output, èhis increase in current output is then exploited for the e C !improvement of aptasensor functionality upon incorporation of the aptamerm for the detection of prostate specific antigent Ohe research in this thesis has been carried out with the intention of contributing to the world of medical researchm more so because of the eversincreasing need for medical care to become accessible to all and not only to those who can afford expensive technologies and treatmen tst e C

2ontents

yedication P ii D -cknowledgements PiiiD

Creface PvD

èable of contents PviiiD

1ist of abbreviations PxvD

1ist of symbols PxviiD

PxxD e C

Oable of contents

;hapter c c, pzntroduction c c,c Nverview of metallophthalocyanines P2CcsD m

1.1.1 Synthesis of asymmetric MPcs 2

1.1.2'Phthalocyanine complexes used in this work 4

c,mpNverview of graphenekbased quantum dots d

1.2.1'The synthesis of GQDs, NGQDs and gCNQDs 9

1.2.2 GQDs characterization and structural determination 10

1.2.3 General applications of GQDs, NGQDs and gCNQDs 13

c,apxold nanoparticles P-u0CsD cd

1.3.1'Synthesis properties and applications 15

1.3.2'AuNPs and their conjugates with MPc in electrochemical sensing 16

c,bpNverview of aptamers cf

1.4.1'Discovery and development 18

1.4.2 Aptamers as biorecognition elements in biosensing 18

1.4.3'Aptamers as bioconjugates for sensing 19

c,d èarget analyte used in this work mc t C

LtdtLIL-cysteine 21

LtdtDIPSA 21

Lt'Iwethods of electrode surface modifications Do

Lt'tLIAdsorption by Ôdrop and dryÕ modification technique 28

Lt'tDIElectrodeposition l self-assembly 28

1.6.3 Electrochemical grafting by reduction and ÔclickÕ reaction 29

LtuITummary of aims of this thesis nd

2hapter D

Dt waterialsm equipment and experimental

n o

DtL waterials nv

2.1.1 Solvents and general materials 39

2.1.2 Synthesis of MPcs and conjugates 39

2.1.3 Quantum dots 39

2.1.4 Biological samples 39

2.1.5 Capillary electrophoresis-mass spectrometry ´CE-MSW 40

2.1.6 Electrode modification 40

DtD Tolution preparation lS

2.2.1 Capillary electrophoresis-mass spectrometry ´CE-MSW 40

2.2.2 Aptamer 41

2.2.3 Electrochemical detection 41

Dtn 0eneral equipment lL

t C Dtl 2apillary electrophoresissmass spectrometry experiments ll m,b,c ;Mkç' experiments bd m,b,m 2' detection bp

Dtd Tynthesis lu

m,d,c ;omplex PLD bg m,d,m ;omplex PDD bf m,d,a éuantum dots b( m,d,b ;onjugation of nanocomposites dc m,d,b,c pp conjugationS éysk;oCc PLDr Tcheme ntd dc m,d,b,m ;ovalent conjugationS xéysv-ptamerr g;0éysv-ptamer and ;oCcPLDv-ptamer PTcheme ntlD dm m,d,b,a 0onkcovalent combination of g;0éysv-ptamer with complex P L

D and P

D D da

Dt' Mlectrode modification dn

m,p,c yrop and dry electrode modification db m,p,m Mlectrodeposition and selfkassemblym Tcheme ltD àaC dd m,p,a Mlectrografting and click chemistryr Tcheme ltD àbC dd Dtu Mlectrode and solution preparation for detection of -T≡ d'

2hapter n

nt 2haracterization d v ntL 2haracterization of 0Bµsm g0Bµs and g2gBµs 'S a,c,c yispersity and size distribution pm a,c,c,c èM2 pm t C ntLtLtD µ4T '' ntLtD Mlemental composition and structure 'o ntLtDtL Mnergy dispersive èsray àMµèC analysis 'o ntLtDtD Iaman spectra uS ntLtDtn 3OHI spectra uD ntLtDtl è-T spectra ul ntLtn µispersitym charge density and colloidal stability oS ntLtntL Keta potential àIC oS ntLtntD 2MsMTHswT ol

3.2 Characterization of MPcs, Complex ´1W and complex ´2W 104

3.3 Characterization of conjugates 105

ntntL',erification of covalently linked conjugates 0Bµs)≡ptamerm g2gBµs)≡ptamer and 2o-càLC)≡ptamer LS' ntntLtL è-T spectra LS' ntntLtD µ4T and zetametry LLS ntntLtn 3OHI spectra LLn ntntLtl Iaman spectra LLd ntntD !! conjugation LL' ntntDtL É,cvis spectroscopy LLu ntntDtD µ4T and zetametry LDS ntntDtn Iaman spectra LDD

3.4 Conclusion 125

Chapter 4

t C lt Mlectrode modification and characterization LDo ltL Mlectrode modification by adsorptionU Oable ltLm group ≡s2 LnS b,c,c ;yclic voltammetry cac b,c,m 'M;2 cag ltD -reparation and characterizat ion of ≡ug-sm 2o-c àDC and aptamer s based electrodes LlL b,m,c Mlectrodeposition of -u0Cs cba b,m,c,c ;yclic voltammetry cba b,m,c,m 'canning electron microscopy P'M2D cbp b,m,mq'elfkassemblyr electrochemical grafting and click chemistry and cbf b,m,aq;yclic voltammetry characterization cdc b,m,bq'M;2 characterization cdd b,m,dqLC' spectra cdg ltn 2onclusions L'd

2hapter d

dt Mlectrochemical detection L u dtL Mlectrochemical detection of 4scysteine L'o d,c,c ;yclic voltammetry cpf d,c,m ;hronoamperometry cgl d,c,a, QineticsS 'can rate studies cgg d,c,b 'tability cg( dtD Ohe electrochemical detection of -T≡ LoS t C dtDtL 0Bµss2o-càcCàppCs≡ptamer conjugates LoS dtDtLtL MHT LoS dtDtLtD 2oncentration studiesU µ-, and MHT Lo' dtDtLtn Ttabilitym selectivitym and reproducibility studies LvS dtDtD Ohe effects of Bµs composition and structureU 2omparing 0Bµsm g0Bµs and g2gBµs Lv' dtDtDtL MHT Lv' dtDtDtD 2oncentration studies using MHT and µ-, Lvv dtDtDtn Telectivitym stabilitym and reproducibility studies DSL dtDtn Hnfluence of w-c substituents DS' dtDtntL MHT DS' dtDtntD 2oncentration studies using MHT DSo dtDtntn Ttabilitym reproducibilitym and repeatability DLD dtDtl ≡ug-ssw-c conjugates DLl dtDtltL MHT DLl dtDtltD 2oncentration studies using MHT and µ-, DL' dtltDtn Mffects of scan rate DLo dtDtltl Telectivitym stabilitym repeatabilitym and reproducibility studies DDS d,a ;onclusions mmb ;hapter p p, àeal sample analyses mmg p,c kconjugates mm( p,m ;ovalently linked conjugates mad t e C 'tn Telfsassemblym electrografting and click chemistry Dnv 'tl 2onclusions Dln

2hapter u

ut Tummarym conclusionsm and prospects Dld utL 1verview of the thesis Dl' utD 3uture prospects and final remarks Dlu

Ieferences Dlv

te C

4ist of abbreviations

-u0Cs . gold nanoparticles qM . binding energy qxM . background electrolyte ;Mk2' . capillary electrophoresis mass spectrometry ;oCc . cobalt phthalocyanine ;' . cyclic voltammetry yqç . crfkyiazabicyclo [d,b,l]undeckgkene y2T . dimethylformamide y2'N . dimethylsulphoxide yC' . differential pulse voltammetry

Mz' . electrochemical impedance spectroscopy

M'z . electrospray ionization

Tèzà . fourier transform infrakred

x;M . glassy carbon electrodes g;0éys . graphitic carbon nitride quantum dots xCM' . general purpose electrochemical system xéys . graphene quantum dots

2Ccs . metallophthalocyanines

0xéys . nitrogen doped graphene quantum dots

02 . neutral marker

C;a . prostate cancer

C'- . prostate specific antigen

'M;2 . scanning electrochemical microscopy te C

TMw A scanning electron microscopy

OMw A transmission electron microscopy

tertsbutyl A tertiary butyl

ÉwM A ultrasmicro electrode

É,cvis A ultravioletcvisible

è-T A èsray photoelectron spectroscopy

èIµ A èsray diffraction