Molecular Interactionsatthe Cellulose-Lignin Interface Exploredvia Molecular Simulation

Josh Vermaas, Gregg Beckham, and Michael Crowley

Fall 2019ACSNational Meeting San Diego, California

August28th,2019 NREL/PR-2700-74305

LigninIntroduction

• Ligninisanaromatic heteropolymerthatmakesup between15-40%ofthedry weightofterrestrialplants

• Largestsourceofrenewable aromatics

• Manypotentialindustrialuses • Implicatedasasignificant

driverofcellwallrecalcitrance

2

LignocelluloseSimulation

Vermaasetal.2015 3

LigninBindstoCellulose…

• Lignincoversroughlya quarterofthecellulose surface

• Doesitcoatthesurface evenly?

• Doesligninchemistry matter?

Vermaasetal.2015 4

…ParticularlyHydrophobicCelluloseFaces

• Prefershydrophobicfaces • Blockscellulasebinding • Canwequantifythethermodynamic

preferencebetweenfaces?

Vermaasetal.2015 5

TheManyFacesofCellulose

• Onlythe200faceis hydrophobic

• Otherprimaryfacesare hydrophilic

• Normalcellulosetwists • Infinitecellulosedoesnot

6

Fernandesetal.2015

200 110

1-10 010

TheNextExperiment

• Construct“infinite”sheetsof cellulosewithdifferentfaces exposedtosolution

• Placeligninderivedcompounds insolution

• Simulate for 200 ns • Determine binding free energies

ofcompoundstoindividualfaces

7

WhatCompounds? OH OH OH OH

O OH

R' R Gua

iaco

l (G) Ph

enol (H)

HO

β1

* *

HO

O O

ββ

* *

* *

OH

OH

O

OH

OH O O O

OH OH

O

Syring

ol (S)

OH

O O α-ester γ-ester Phenolics OH OH

O *

*

OH

OH OH Ca

tech

ol (C)

OH HO 4O5 HO

OH β5 OH

OH

* O HO

O HO O

OHHO

*

OH O

R R' R R' OH

* *

Chiralcenter

OH O OH

R

OH OH R' OH OH

Monolignols 5-5 αO4 & βO4 βO4 8

PotentialBindingMetricsforFreeEnergyDetermination

• Free energy isrelatedto probability

• Trajectoriescanbeusedto determinerelative probabilities

• Howdowedefineabound vs unbound state?

9

DistanceandContactMetrics, Compared

• Distance • LigninCenter of

masstocellulose centerofmass

• Veryeasytoexplain • Contactnumber

• Pairwisecontacts betweencellulose andlignin

• Isnotbiasedby ligninshape

Unb

ound

Bo

und

Unb

ound

10

CelluloseBindingforMonomers

• Hydrophobic200face predominantforbinding

• Ferulatepreferssolution • Fitswellwithits

physiologicalrole • 110facebetterfor

bindingthantheother OH OH OH OH OH OH OH OH OH OH OH MeO OMe OMe OH MeO MeO OMe OH MeO OH MeO MeO hydrophilicfaces

OH

O OH OH O O OH O OH

11

MultimericBinding

• 200>>110>010>1-10 • Planarligninmoleculeslike

estersdemonstrateparticular affinitytothe200face

• Comparisonsbetween stereoisomerssuggestlonger simulationmaybebeneficial

12

��

����

1

2

3

4

5

6

CelluloseFace-DependentBindingRelationships

100

G

bindi

ng

(kT

) 0

-

-

-

-

-

-r2 = 0.77 r2 = 0.56 r2 = 0.44

P henols Alcohols Carboxylates ↵O4& O4 O4

55 4O5 Esters 1 5

-2 0 -2 0 -2 0 110 Gbinding (kT) 1-10 Gbinding (kT) 010 Gbinding (kT) 13

14

HowDoesBindingScalewithPolymerSize?

• Monomersanddimersarenot perfectmodelsforreallignin

• Drawfromestablishedlignin polymerlibraries

• Determine ligninbinding affinity

UnbiasedLigninContactstoCellulose

15

TechnicalChallenges

• Bindingisspontaneousand irreversibleontypicalMD timescalesforlargerlignin

• Usereplicaexchangeumbrella samplingonacontact-number reactioncoordinatetoestimate binding free energy

16

SurfaceAreaComparison

• Contactnumberasdefinedisa strongproxyforcontactsurface areabetweenligninandcellulose

16.0 kDa lignin polymer 1200 200

110

1-10 1000 010

800

600

400

200

0

0 500 1000 1500 A2) 17 Lignin-Cellulose Contact Area (˚

Lig

nin

-Cel

lulo

se C

onta

cts

BindingFreeEnergyProfiles

18

SizeDependenceofLignin-CelluloseInteractions

• Bindingfreeenergygrows withthelogarithmofthe ligninmass

• Trendisweak, highly inconsistent

19

• Bindingfreeenergygrows directlywiththenumberof contactspresentatthefree energy minimum

• Slopesareconsistentacross faces

CelluloseFace 200 0.0111 110 0.0083 1-10 0.0107 010 0.0107

Summary

• Bindingstrengthquantificationcaninformligninmodification • Ligninrelatedcompoundsprefer tobindtohydrophobic cellulose

facesbyaboutafactorof2 • Mayberelatedtothe“flatness”ofthe200face, whichfits

wellwithplanararomaticrings, creatingmorenonspecific interactionsites

• Lignincontactnumber/contactareaismoreimportantthan polymersizeindeterminingbindingstrength • Ligninagglomerationisnotconsidered, butwouldlikely

additivelyincreasebindingstrength 20

GreggBeckham MichaelCrowley

Questions?

www.nrel.gov

This work was authored by the National Renewable Energy Laboratory, operated by Alliance for Sustainable Energy, LLC, for the U.S. Department of Energy (DOE) under Contract No. DE-AC36-08GO28308. Funding provided by the U.S. Department of Energy Office of Energy Efficiency and Renewable Energy Bioenergy Technologies Office. The views expressed in the article do not necessarily represent the views of the DOE or the U.S. Government. The U.S. Government retains and the publisher, by accepting the article for publication, acknowledges that the U.S. Government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this work, or allow others to do so, for U.S. Government purposes.