alkahest (paracelsus, 1491-1541): context and strategy · 2019-04-05 · -alkahest (paracelsus,...

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The InBioSynSolv Project

Virtual laboratory for synthons and biosolvent design based on reverse

molecular engineering

[email protected]

Financing: French ANR program CP2D 2009

Colloque ANR Chimie Durable - Lyon 19 sept. 2012Colloque ANR Chimie Durable - Lyon 19 sept. 2012

The InBioSynSolv Project

• Accreditation by the pôles de compétivitité AXELERA, MAUD• 4 years project : 01/10/2009 – 30/09/2013• total budget: 2.9 M€ / 1.2 M€ financed

Computer and product modeling

Solvent chemistry and formulation

Agro-sourced solvents

Solvents and applicationsInBioSynSolv

leader

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Context and strategy

Designing green « alkahests »

Top-down vs bottom-up approaches

Colloque ANR Chimie Durable - Lyon 19 sept. 20123

In Silico design of « green alkahests »

- Alkahest (Paracelsus, 1491-1541): • hypothetical universal solvent, having the power to d issolve

every other substance.


Bio-solvents

Propertyrequirements

Primary functionSecondary

EEHS-related

IN

glycérolfructose

omega3

Synthons & Building blocks

Plants

IN

Reverse formulation

« clean » ecosynthesis

Life cycle assessment

OUT

Molecules & mixtures

InBioSynSolv

air

waterhealth

food

constraints IN

REAChregulation

price

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Profile of an ideal green solvent

- Major environmental and economic criteria• Non-VOC:

• Pvap < 10 Pa (Europe) or Eb > 250°C (USA)

• Low toxicity to humans and environment: • Non-CMR, biodegradable

• High flash point: • Considered as « non flammable » when Flash Point > 55 °C

• Reasonable price: • 0.5 to 20 €/kg for high value applications

• Synthesized from bio-sourced building blocks not co mpeting with food resources

- Major physico-chemical and process properties• High solvency power• Easy to recover and regenerate at the end of the pr ocess • Miscible to water for some applications


The InBioSynSolv strategy


TO

P-D

OW

N A

PP

RO

AC

H

Bio-sourced building-blocks

Bio-sourcedsolvents candidates

Physico-chemical properties

Mp : -66,7 °CPvap : 20 PaBp : 351 °C

δD : 18 MPa1/2

δP : 08 MPa1/2

δH : 14 MPa1/2

Target functionalproperties

Liquid Solvent for dyes, lacquers, pharmaceuticals…

Non VOC,Non CMR

BO

TT

OM

-UP

AP

PR

OA

CH

Relevant chemicaltransformations

Mathematicalmodels

Prediction of functional properties

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Finding renewable resources pools

Synthons or raw biomass?


Bio-sourced synthons

- Use of synthonsrather than raw biomass

• more reliable, and less variable

- Some results:• 10 main pools of

renewable resources have been identified from the literature


(Angew. chem. Int. Ed. 2007)

OilsRaw mat.

Synthesissteps

End product

Synthons

End product

End product

Synthons

Biodieselraw mat.

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The Bottom-Up approach: In-silico guided synthesis of green solvents

Finding of renewable resources pools

Relevant eco-friendly chemical transformations

Automatic generation of possible molecules

A posteriori evaluation of the molecules performance


the Bottom-Up approach

- Relevant eco-friendly chemical transformations


Bibliographical sources:

�� Synthesis of petrochemical commodities

�� Transformations of bio-based molecules

�� Synthesis of pharmaceuticals

> 500 reactions

have been found

Selection criteria of relevant transformations:

�� Efficiency (good yields)

�� Mild conditions (temperature, pressure)

�� Greenness (atom economy, safe reactants)

�� Cost effectiveness

�� Validation by Rhodia

relevant chemical transformations

the Bottom-Up approach

- Computer aided synthesis �� the GRASS program• GeneRator of Agro-based and Sustainable Solvents


Building block

Relevant ChemicalTransformation

Co-reactant

Systematic & flexible approach to generate thousand s of virtual derivatives from any pre-defined buildin g block

Virtual Derivatives

The Top-Down approach

Computer Aided Product Design: Finding molecules that match target properties


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top-down CAPD

- Computer Aided Product Design �� IBSS Software tool• Set a priori target values for many properties and find / build

candidate molecules and mixtures that satisfy them


Property models Target

properties

Target

properties

Building

blocks

Building

blocks

Mixture buildingMixture building

Process model

Group contribution 1er order

Molecular descriptors

-CH2, -OH, -NO2, …

-C, -N, -O-, =C, …

Chemical

fragments &

database

Set of molecule /

mixture candidates

Check performanceCheck performanceGenetic algorithm

Objective function

top-down CAPD

- Computer Aided Product Design

�� the IBSS Software tool• Software engineering

• UML2• Component/object oriented

architecture• C#, Java

• XML Standard input files


Man-Machine Interface

Building Blocks

DatabaseSearchcomponent (IBSS)

PropertyCalculation Model

Library

Activity process in IBSS

top-down CAPD

- Matching the bio-sourced challenges• Customize the properties• Customize the mixture structure

• Molecules• Composition

• Customize the molecule structure• Fragments

– e.g. from renewable pools

• Building blocks– Compliant with sustainability


a.i. solventwater scentmolecule

composition 5% y%10%<x<30% <2%

Building

blocks

Chemical

groups

built from

built from

Molecule Fragment

Specified Free Specified Free

Performance evaluation

Global performance index

Solvent power


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Performance: global index

- Property • Estimation models • Relative weights

- Performance calculation• Select a performance

function for each property

• near

• above

• below

• Global index: max perf(M)


Property name Weight Target Mixture Model

Pure Compound Model

Molecular weight 1 <200 g/mol

Flash point 1 >323.15K linear Catoire 2006

Vapor pressure 1 <0.00267 bar linear Riedel, 1954

RED 4 <0 Non linear HSPiP

Env.Waste 0.2 >8 linear Weis, 2009

Env.Impact 0.2 >8 linear Weis, 2009

Health 0.2 >8 linear Weis, 2009

Safety 0.2 >8 linear Weis, 2009

LCA 0.2 >8 linear Weis, 2009

Viscosity (300K) 1 [0.8;1.4] cp Tamura 53 Conte, 20 08

Surface tension@298K 1 [30;45] dyn/cm2 Teja & Rice Conte, 2008

Density 1 [0.9;1.1] linear HSPiP

Log(Ws) 4 >4 mg/L linear MG 2002

Finding an aqueous solvent to wash blanket ink

Performance: solvent power

- Hansen Solubility parameter• Split of Hildebrand δδδδ into:

• δδδδ D dispersive contribution • δδδδ P polar contribution• δδδδ H H-bond contribution

• Principle• The closer the HSP of two

materials, the more likely it is that they have higher affinity than had their HSP been farther apart

• Solvents • within the sphere should solubilize

the solute• The closer to the center, the better


δδδδD

δδδδP

δδδδH

http://www.hansen-solubility.com/index.php

Performance: solvent power

- COSMO σσσσ-potential curves of typical solvents


σσσσ (e/nm2)

µµµµ

Hexane

Non H+ donorNon e - donor

Water

Atypical profile in the middle=> Lipophobicity

Acetone

e- donor Slightly H + donor

Chloroform

Pyridine

Very good e - donor

Trifluoroethanol

Very good H + donorSlightly e - donor

Examples

Application to glycerol

Augeo SL191®, an industrial new solvent


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Green building-block

Co-reactants

pre-defined chemical

transformations

+ GRASS

Glycerol derivatives


75 435« Bio-sourced

Potential Derivatives »-ols, acids, -ones, etc..

30977

21562

83834722

4211

33662214

All simple derivatives of glycerol reported on the literature

have been found by GRASS within 5 generations




- Bottom-Up: GRASS• Performance index

- Top-Down: CAPD• Generations

• > 1.3 Millions structures from10 renewable pools

• Performance• > 1000 structures with

performance index > 0.99


100%

30977

21562

83834722

4211

33662214

Low evaporation rate solvents

remain at the final step. They are

responsible for the leveling of the

film assuring the quality of the film.

Glycerol cetal AUGEO SL 191

- AUGEO application: car refinishing


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- AUGEO SL 191 a new industrial glycerol-based solven t

HO OH

OH H+

HO OO

O+

Solketal(= Augeo SL191®)

73% of the molecule weight comes from a renewable source(could be 100% with bio-acetone)

Brent

Phenol

Acetone

Soya

Biodiesel

Vegetal Oil

Natural Gaz Methanol

glycerolPinhão Manso

Colza

Co-product

Co-product

AUGEO SL 191



ENVIRONMENTAL PROPERTIES

• Biodegradabillity Not readily biodegradable

• Bio-accumulation Not likely to bioaccumulate

• Acute aquatic toxicity Not classified

• Chronic aquatic toxicity Not classified

TOXICOLOGICAL PROFILE

• Acute toxicity Not classified

• Skin corrosion / irritation Not classified

• Serious eyes damage / irritation Category 2A*

• Respiratory / Skin sensitization Not sensitizing

• Germ Cell Mutagenicity Not classified

• Carcinogenicity Not classified

• Reproductive Toxicity Not classified

SAFETY

• Boiling point 183°C-191 °C• Flammability Category 4• Flash Point (closed vessel) 91°C (combustible)

*Category 2A means that AUGEO SL 191 is irritating to eyes with reversible effects



- AUGEO: Substitute for glycol ethers in paints and varnishes

OOHO

Boiling Points 189 °C 190 °C

σσσσ-Potential curves

-1,2

-1,0

-0,8

-0,6

-0,4

-0,2

0,0

0,2

0,4

0,6

-3 -2 -1 0 1 2 3

HO

OO

C1P2 and Augeo SL191 exhibit similar evaporation rates and solvency properties



- AUGEO application: car refinishing

Solvents Boiling Point °C Composition %

Ethyl Acetate 77 18Ethanol 79 57

Isopropanol 82 15Butanol 118 5Solketal

(Augeo SL 191) 189 0

Dipropylene Glycol Monomethyl Ether 190 5

• Similar application results:

• Same evaporation kinetic of the solvent blend

• Same solubility power all along the drying

• Same paint film caracteristics (gloss, adhesion,

chemical resistance…)

• With better tox/ecotox at a comparable price



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InBioSynSolv conclusions

- Main result: • Combine in silico tools

• bottom-up (GRASS oriented synthesis tool)• top-down (CAMD – reverse engineering)

• The cooperative effect• No single partner can provide the solution alone

– Chemist expert – Industrial expert – Modeling expert

» Chemical engineering» Computer engineering

• Publications:• 1 art., 4 art. in prep., 13 proceedings • patents on chemicals in prep.• GRASS and IBSS software : non patentable

– IBSS property library component : licence to

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Thank you for your attention!

Acknowlegments


Alchemists searching for green ALKAHESTS

alkahest (paracelsus, 1491-1541): context and strategy · 2019-04-05 · -alkahest (paracelsus,...

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