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Methusalem, Advisory Board Meeting, June 24, 2013

Kinetic modeling usingchemo-informatics: Genesys

1http://www.lct.ugent.be

LaboratoryLaboratoryLaboratoryLaboratory forforforfor

Chemical Chemical Chemical Chemical TechnologyTechnologyTechnologyTechnology

Nick Vandewiele, Kevin Van Geem, Marie-Françoise Reyniers, Guy B. Marin

Methusalem, Advisory Board Meeting, June 24, 2013

Kinetic models grow larger and larger

2T.F. Lu, C.K. Law / Progress in Energy and Combustion Science 35 (2009) 192–215

Methusalem, Advisory Board Meeting, June 24, 2013

Genesys: computer generated kinetic models

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Initial

reactants

Mechanism Kinetic model

Automatic calculation of :

• Species thermochemistry

• Elementary reaction kinetics Vandewiele et al. Chem. Eng. J. (2012)

http://www.lct.ugent.be/

Methusalem, Advisory Board Meeting, June 24, 2013

Reaction network generation

k6

k15

k1 k2

k3

k4

k5

k7

k8

k9

k10k11

k12

k13

k14

Molecules Unique Representation

Thermo-dynamics

Reactionfamilies

Reaction Identification

Kinetic Parameters

Reactionrules

Kinetic model enlargement

Termination criterion

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• Graph theory and algorithms can be applied: main

methods for chemistry apps:

• Sub-graph matching ~ functional group query

• Equivalence test ~ structure database query

Graph representation of molecules

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InChI=1S/C2H4O2/c1-2(3)4/h1H3,(H,3,4)

Defining sub-molecular patterns:

SMARTS (SMILES Arbitrary Target Specification)

CHCH

CH

H

CH3

CH3

Methusalem, Advisory Board Meeting, June 24, 2013

Andrew Dalke’s EuroQSAR 2008 Poster

(http://www.dalkescientific.com/)

Don’t re-invent the wheel: chemo-informatics

6Multiple ligands alignment within 3D field potential from Qmol LLC.

Methusalem, Advisory Board Meeting, June 24, 2013

Genesys: integration of CDK

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Reaction families in Genesys

• Add chemistry you know that is relevant;

• Constrain reaction families as much as possible

CC

CHC

R

R

R

R

R

RC

CC

C

R

R

R

R

R

R

H+

CC

CC

R

H

R

R

R

RC

CC

C

R

R

R

R

R

H+

C C C

C R

R

R

R H

H+C C C C

R

RR

R

CC

CH

R

R

R

R

CH+C

CC

R

R

R

R

Single bond between radical C and H-bearing

C

sp² C’s in double bond, not sp

Radical C not part of ring

E.g. “C-H β scission in presence of double

bond in γ position”

C

R

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Methusalem, Advisory Board Meeting, June 24, 2013

Defining reaction families: pattern, recipe, constraints

C=C-C(H)-[C;v3]A [C;v3]-C(H)-C=CB H-C([C;v3])-C=CC C(C=C)(H)-[C;v3]

CC

CC

H

Center A

Center B

Center C

CHCH

CH

H

CH3

CH3

Submolecular pattern :

Reactive center:

Molecule Constraints:

MINIMUM Carbon COUNT 5MAXIMUM Carbon COUNT 10TOTAL NUMBER OF SINGLE ELECTRONS 1

RECIPE:

(1) BREAK BOND B,C

(2) INCREASE BOND A,C

(3) LOSE RADICAL A

(4) GAIN RADICAL B

SMARTS:

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THERMOCHEMISTRY

ESTIMATION

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Ideal gas TD Properties: Benson Additivity

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Nature of GAVs, ca. 1000 unique groups

Filling the Benson Database

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Sabbe et al. J. Phys. Chem. A 2008, 112, 12235–12251

Sabbe et al. J. Phys. Chem. A 2005, 109, 7466-7480

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NETWORK GENERATION

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Network generation: HMPA

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HMPA

P N

C

H

P NH

CH2H

P NP

N

OO

P N

C

O

H

P NH

C

OH

C

N

N

CR

R

P

N

C

P

C

N

O

O

PH

NN

CH2

O

C

N

N

PH

O

Define reaction families

Generated species

Methusalem, Advisory Board Meeting, June 24, 2013

BUILDING KINETIC MODELS

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Methusalem, Advisory Board Meeting, June 24, 2013

Building kinetic models: Kinetic group additivity

Saeys et al. 2004, AIChE J.

GAV Library

* Ci-(H)2(C) -1.161 -3.6

* Ci-(C)2(H) -0.884 -8.3

* Ci-(C)3 -0.342 -14.7

* Ci,d-(H) +0.407 -10.6

* Ci,d-(C) -0.009 -14.6

* ...

SMARTS C1 log(A) Ea

GAV Library

* Si-(H) +0.101 -20.2

* Si-(Cd) -0.273 +26.6

* Si-(CS) -0.788 +22.0

* Si-(Cd) +0.566 +35.1

* Si-(Cb) +0.406 +24.3

* ...

SMARTS S1 log(A) Ea

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Sabbe et al. ChemPhysChem 2008, 9, 124 – 140

Methusalem, Advisory Board Meeting, June 24, 2013

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Chemistry knowledge:

A.G. Vandeputte, The thermochemistry and Decomposition Mechanism of

Organosulfur and Organophosphorus Compounds, 2012 (Ph.D)

Kinetic data:

Hydrocarbon reaction families:

Additions and β-scissions: Sabbe et al. ChemPhysChem 2008, 9, 124 – 140

Hydrogen abstractions: Sabbe et al. PCCP, 2010, 12, 1278–1298

Sulfur reaction families:

Hydrogen abstractions : Vandeputte et al. PCCP, 2012;14(37):12773-93

Homolytic substitutions: Vandeputte et al. 2012 (Ph.D)

Generated model:

3612 reactions

151 species

Alkylsulfide thermal decomposition

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Ethyl-methyl-sulfide pyrolysis: validation

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EMS pyrolysis: quantitative analysis

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EMS conversion: 14%

Temperature: 1013K

Residence time: 0.2s

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Conclusion

• Genesys: automatic reaction network generation framework for quantitative models

– Integrated with open-source chemo-informatics library (CDK)

– Generally applicable:

• Support for many elements

• Support for many chemistries

– Quantitative structure – property relationships easily

implementable

• Ideal Gas TD Properties

• Kinetic expressions for elementary reactions

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Methusalem, Advisory Board Meeting, June 24, 2013

Acknowledgments

LCT @ UGent:

• Steven Pyl, Carl Schietekat, Thomas Dijkmans, Ruben De Bruycker

• Aäron Vandeputte, Maarten Sabbe, Ruben Van de Vijver

Funding:

• Long Term Structural Methusalem Funding by the Flemish

Government

• Fund for Scientific Research - Flanders21

Methusalem, Advisory Board Meeting, June 24, 2013

THANK YOU!

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