KINETICDATAANALYSISAND

GRAPHING

Dr. Chukwuemeka Isanbor Department of Chemistry, University

of Lagos, Nigeria.

Overview

§  ChemicalKine>cs§  ChemicalKine>csProcedures§  NucleophilicAroma>cSubs>tu>onReac>ons§  SomeChallenges§  AcaseforOpenScienceinAfrica.

ChemicalKine>cs

•  The area of chemistry that is concerned with the speeds, or rates, of reactions is called chemical kinetics. Chemical kinetics involves the study of the rates and mechanisms of chemical reactions.

•  Chemical kinetics is a subject of broad importance. •  It relates, for example, to how quickly a medicine is

able to work, to whether the formation and depletion of ozone in the upper atmosphere are in balance, and to industrial problems such as the development of catalysts to synthesize new materials.

TheObjectsofChemicalKine>cs

There are broadly two separate, although, related objects of chemical kinetics; rates and mechanisms.

•  The analysis of the mechanisms by which reactions occur i.e. the sequence of elementary steps giving rise to the overall reaction.

•  The determination of the absolute rates of the reaction of its individual steps.

Kine>cstudiesprovidevaluableprac>calinforma>onontherateunderexperimentalcondi>onssuchas;

•  reactantsconcentra>on,•  temperatureand•  mediumofreac>on. This is then used to provide the basis fordetermining the mechanism by which areac>onoccurs.

Kine>cProcedures

•  Thestar>ngpointofmostkine>cinves>ga>onof chemical reac>ons is thedetermina>onofthereac>onrateanditsdependentupontheconcentra>onofthespeciesinvolved.

•  The overall rate of a reac>on rate is notnormally measured directly; rather, theconcentra>on of the reactant or product ismonitoredasafunc>onof>me.

Mechanis>c understanding of chemical reac>ons drivesresearch and guides teaching of reac>vity in chemistry.Upper-level physical organic or organometallic chemistrycourses oQen discuss reac>onmechanism in detail, in thecontextofprototypicalexamplereac>ons.

Kine>cAnalysisofComplexSystems.

EnzymeKine>cs

Transi>on-StateTheoryandTemperatureDependence.

NucleophilicAroma>cSubs>tu>on

1.Nucleofugality2.Natureofnucleophile3.Stereoelectroniceffects4.Solventeffects.5.Basecatalysis

NucleophilicAroma>cSubs>tu>on(SNAr)Reac>ons

•  Of the 1086 unique small molecules approved by the U.S.Food and Drug Administration (FDA), 640 are found in their assemblage, where at least one nucleophilic aromatic substitution reaction (SNAr) is involved.

•  SNAr reaction is used once or more in synthetic schemes en route to the following best-selling FDA-approved small molecules: abacavir, imiquimod, erlotinib, levofloxacin, moxifloxacin, pioglitazone, rosiglitazone, pazopanib, febuxostat, itraconazole, ziprasidone, olanzapine, and timolol.

•  A number of these drugs are listed on the World Health Organization’s List of Essential Medicines.

•  SNAr reaction is an important reaction within industrial circles.

IsleyN.Aetal,Org.Le/.,2015,17,4734-4737

LeavinggroupeffectsontheMechanismofSNArReacHons

J.Phys.Org.Chem2004,17,65-70

DataAnalysis§  Quantitative data for individual rate coefficients was

obtained by a combination of kinetics data software, and spectrophotometry.

§  This involves following a time dependent change in a chemical reactions.

§  Spreadsheet program can then be used to analysed the data for parameters of interest. Examples of such spreadsheet program include;

Ø Macromath Scientist Ø OriginPro Ø Sigmaplot Ø SimFit

(a)UV-VisSpectrumof5×10-5moldm-32,4,6-trinitrodiphenylamine(b)Kine>ctracesinvolving5.0×10-5moldm-3of3.1and0.01moldm-3anilineinacetonitrile,λ=

365nmat250C

Time/ s

Absorbance0.0 0.2 0.4 0.6 0.8 1.0 1.2

( x 103)

0.0

0.2

0.4

0.6

0.8

Time/ s

Absorbance

( x 103)

0.0 0.2 0.4 0.6 0.8 1.0 1.20.0

0.2

0.4

0.6

0.8

( x 103)

0.0 0.2 0.4 0.6 0.8 1.0 1.20.0 0.2 0.4 0.6 0.8 1.0 1.2

( x 103)

0.0

0.2

0.4

0.6

0.8

0.0

0.2

0.4

0.6

0.8

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

300 320 340 360 380 400 420 440 460 480 500

WAVELENGTH/nm

ABSORBANCE

0.00 0.02 0.04 0.06 0.08[ANILINE]

0.00

0.02

0.04

0.06

0.08

0.10

0.12

0.14

0.16

0.18

0.20

k

PLOT OF k Vs [AMINE] FOR THE REACTION OF 2,4-DINITROPHENYL-2,4,6-TRINITRO- PHENYL ETHER WITH ANILINE IN ACETONITRILE

A

A

€

kA =K1k2 +K1kAn An[ ]

1+k2k−1

+kAn An[ ]k−1

0.00 0.02 0.04 0.06 0.08[Aniline] mol dm

0.00

0.02

0.04

0.06

0.08

k dm

m

ol s

-3

-3

A

-1

-1

3a 3f 4f

Table5.Summaryofratedataforthereac>onof4dwithring-subs>tutedanilines2,a-linacetonitrileat25°C.

Substituent(s), R K1k2 (dm3 mol-1 s-1)

K1kAn (dm6 mol-2 s-1)

kAn/k-1 (dm3 mol-1)

k1 (dm3 mol-1 s-1)

kAn/k2 (dm3 mol-1)

a, 4–OMe 2.9 ± 0.3 90 ± 10 5 ± 1 18 ± 5 31 b, 4–Me 0.68 ± 0.05 16 ± 1 3.5 ± 1 4.5 ± 1.5 24 c, 3-Me 0.18 ± 0.05 4 ± 0.5 2.5 ± 1 1.6 ± 0.5 22 d, Ha 0.08 ± 0.01 2.2 ± 0.2 2.7 ± 0.5 0.8 ± 0.3 28 e, 4–F 0.045 ± 0.01 1.25 ± 0.1 2.5 ± 0.5 0.5 ± 0.2 28 f, 4–Cl (5 ± 1) × 10-3 0.23 ± 0.02 1.8 ± 0.5 0.12 ± 0.06 46 g, 3–Cl (8 ± 1) × 10-4 0.026 ± 0.004 1 ± 0.5 0.026 ± .01 33 h, 2,4–Me2 0.024 ± 0.004 0.2 ± 0.05 <1 8

i, 2–Me (4.5 ± 0.5) × 10-3 0.04 ± 0.005 <1 9

j, 2–Et (1.8 ± 0.4) × 10-3 0.011 ± 0.003 <1 6

k, 2–F (1 ± 0.2) × 10-4 (8 ± 1) × 10-3 <1 80

l, 2,6–Me2 (6 ± 1) × 10-5

NucleophilicHeteroaroma>cSubs>tu>on

N

OPh

O2N

NO2

N

OEt

O2N

NO2

4 5

N

OR

O2N

NO2

4 or 5 6

N

OR

NO2

NHR1R2

H

O2N

N

RO NHR1R2

NO2

O2N N

RO NHR1R2

NO2

O2N

N

OR

NO2

NR1R2

H

O2N

N

NR1R2

O2N

NO2

+ 2R1R2NHk6

k-6+ R1R2NH

kAmH+

kAm + NH2R1R2

7

k2

k-2

+ R1R2NHk'Am

k'AmH+

+ R1R2NH2

k4

+ ROH + NHR1R2

10

8 9

a R1R2NH = n-butylamineb R1R2NH = pyrrolidinec R1R2NH = piperidine

Scheme 1

Kine>cEqua>on

[ ][ ] [ ]

+2 +

-66 Am AmHfast

-6 Am -6 Am

k .k AmHk k Amk = +

k + k Am k + k Am

⎡ ⎤⎣ ⎦

[ ][ ] [ ]

22 B

slow 2-2 B c,6

+

k k Am 1k = . k + k Am K Am

1+AmH

⎛ ⎞⎜ ⎟⎜ ⎟⎜ ⎟⎜ ⎟⎜ ⎟⎡ ⎤⎣ ⎦⎝ ⎠

AppliedPhotophysicsSX-17MVStopped-flowSpectrometer

X-RayCrystalStructureDetermina>on

Figure 2. Independent molecules I (left) and II in the structure of 3b, projected on the plane of ring A. Minor (10%) orientations of the CF3 groups are not shown.

DepositedintheCambridgeCrystallographicDataCentre(CCDC)

SmarterChemistry

Smarterchemistryisaboutconnec>ngideasand connec>ngpeople. It beginswithfindingrelevantinforma>on,likedataaboutchemicalreac>onsandchemicalcompounds.

RSC’sChemSpider

>34millionchemicalsfrom>500sourcesand>40,000usersperday

SciFinder

SciFinder® is a research discovery applica>on thatprovides unlimited access to the world's mostcomprehensive and authorita>ve source of references,substances and reac>ons in chemistry and relatedsciences.SciFinderoffersaone-stopshopexperiencewithflexiblesearch and discover op>ons based on user input andworkflow.Youcansearchforsubstances,reac>ons,andpatentandjournalreferencesany>me,anywhere.

Computa>onalChemistry

•  Computa>onal chemistry isnowwidelyused to studythe fundamental proper>es of atoms,molecules, andchemical reac>ons, using quantum mechanics andthermodynamics.

•  Computa>onalchemistsusemathema>calalgorithms,sta>s>cs, and large databases to integrate chemicaltheoryandmodellingwithexperimentalobserva>ons.

•  Some computa>onal chemists create models andsimula>ons of physical processes, and others usesta>s>csanddataanalysistechniquestoextractusefulinforma>onfromlargebodiesofdata.

Computa>onalChemistryvsComputerScience

•  Computa>onalchemistryisnotthesameascomputerscience, although professionals in the two fieldscommonlycollaborate.

•  Computer scien>sts devote their >me to developingand valida>ng computer algorithms, soQware andhardwareproducts,anddatavisualiza>oncapabili>es.

•  Computa>onal chemists work with laboratory andtheore>cal scien>sts to apply these capabili>es tomodelling and simula>on, data analysis, andvisualiza>ontosupporttheirresearchefforts.

ToolsofaComputa>onalChemists

Toolsofcomputa>onalchemistsinclude§  electronicstructuremethods,§  moleculardynamicssimula>ons,§  quan>ta>vestructure–ac>vityrela>onships,§  cheminforma>cs,§  fullsta>s>calanalysis.

Using computational chemistry software you can in particular perform: • electronic structure determinations, • geometry optimizations, • frequency calculations, • definition of transition structures and reaction paths, • protein calculations, i.e. docking, • electron and charge distributions calculations, • calculations of potential energy surfaces (PES), • calculations of rate constants for chemical reactions (kinetics) • thermodynamic calculations- heat of reactions, energy of activation, etc • calculation of many other molecular and bulk physical and chemical properties.

Op>mizedStructures

Oloba-Whenu&C.Isanbor,J.Phys.Org.Chem,2015

CurrentResearch

•  Dinitroanilinesandanaloguesarepromisingnewandinexpensivedrugcandidatesagainstdiseasescausedbyprotozoanparasites.

•  Our project is aimed at providing a precisemechanism for the mode of interac>on ofdinitroaniline-basedan>parasi>cdrugcandidateswithcellularthiols.

•  This interac>on is believed to be important tothe inhibitory ac>vity of these drugs candidatesagainstprotozoaparasites.

Challenges•  Lackofanaly>calequipment-NMR,Stopped-flowspectrophotometerworksta>onforfastkine>cs.

•  Lackedofopenaccesstohighperformancecompu>ng(HPC)resources.

•  Acquisi>onofmul>userlicensedsoQwareforchemicalmodellinganddataanalysis.

•  Lackofins>tu>onalaccesstoelectronicdata•  Inadequatecurrentliteratureforteachingandresearch.

•  Poorfundingforpostgraduatestudies.

OpenScienceforAfrica

Afast,openjournalpublishinghighqualityresearchacrossallofscience,engineeringandmathemaHcs

Acknowledgements.

LateEmeritusProfessorThomasAEmokpae

EmeritusProf.MichaelRCrampton

WorldLaboratory,Switzerland.RoyalSociety,England.RoyalSocietyofEdinburgh,ScotlandRoyalSocietyofChemistryCRC,UniversityofLagos.