Download Graduate Category: Engineering and Technology Degree Level: PhD in Chemical Engineering Abstract ID# 1106

Graduate
Category:EngineeringandTechnology
DegreeLevel:PhDinChemicalEngineering
AbstractID#1106
Multi-ScaleMolecularModelingofTetracyclicRosetteNanotubes
ArthurGonzales III, Belete Legesse, TakeshiYamazaki, Hicham Fenniri*
Abstract
Results
Rosettenanotubes(RNTs)aresoftorganicnanomaterialsselfassembledunderaqueousconditionsfromWatson-Crickinspired
guanine-cytosine(G∧C)hybridbuildingblockswithcomplementary
hydrogenbondingsites.Thesematerialshavesubstantialdesign
flexibilityandarangeofapplications,whichispartlyattributedto
theirdiversesurfacefunctionalizationandachemically/physically
tunablechannelforguestmoleculeloading.Severalstudieshave
establishedtheirbiocompatibilityandapplicationsinnanomedicine
suchasincoatingsformedicaldevices,materialsfortissue
engineering andfordrugdisplayanddelivery.
Withnovelapplicationsinmind,particularly,drugdelivery,anew
tetracyclicG∧Cmotif,theyGC,wasdesignedtoselfassembleinto
RNTinwater. ToaidinthecharacterizationofthisnewRNT,multiscalemolecularmodelingtechniqueswereappliedtopredictits
structureinwater.Moleculardynamics(MD),molecularmechanics
(MM),andthestatisticalmechanicaltheoryofsolvation,alsoknown
asthe3dimensionalreferenceinteractionsitemodel(3D-RISM)
theorywere appliedtopredicttheconformationofRNTs.MMwas
usedtodeterminethepossibleconformationsoftheindividual
motifs.Fromthese,RNTmodelswerebuiltandMDsimulations
were runtodeterminethestabilityandprobablestructureofthe
nanotubes.TheresultssuggestthattheyGC motifcaneitherforma
6-memberedor7-memeberedringstacks.3D-RISMintegral
equationswerethensolvedforthesystemtodeterminethe
energeticsandtoproposeaself-assemblypathwayfortheRNTs.
Currently,experimentsare beingdonetoverifythestructureofthe
RNTs.
TheMDsimulationssuggestthat
A
thereare morethanonepossible
RNTconfigurations.Indeed,visually
theRNTformedfrom7-membered
ringslookmorestableasthecircular
structureofthe6-memberedrosette
deforms.AndtrajectoryRMSDsof
thenitrogenatomsalsoindicatesthe
samething.
B
C
Thefinalmodelsofthetwosystems
are shownbelow.
System1:6-memberedrosette
• Diameter =19Å
• StackingDistance=3.8Å
• Staggered Angle =12.8°
D
System2:7-memberedrosette
Figure 2. MD simulation results. Middle
rosette of System 1 (A) and System 2 (B).
RMSD of the trajectories of the nitrogen
atoms of the middle rosettes of System 1
(C) and System 2 (D).
• Diameter =25Å
• StackingDistance=3.9Å
• Staggered Angle =12.2°
Introduction
A
B
C
D
3D-RISManalysisofthefinalRNT
modelsshowsanegativelytrending
associationfreeenergy,which
indicatesformationofrosettefrom
withavailable motifsisspontaneous.
Andboththe6-memberedrosette
andthe7-memberedoneare
possible.
0
1
2
3
4
5
6
7
0
-10
-20
-30
Sys tem 1
Sys tem 2
-40
-50
-60
Motif N umber
Figure 4. Association free energy of the
two systems.
Conclusion
Methods
• 2 RNTs were then built from the
minimized motifs and minimized.
• 100 ns MD simulations were run to
determine the stability and the most
probable structure of the RNTs.
• 3D-RISM was used to determine
the energetics and to propose a selfassembly pathway for the RNTs.
B
Figure 3. Final RNT models. Rosette of System 1 (A) and System 2 (B). Twenty-ring
stack RNTs of System 1 (C) and System 2 (D).
Objectives
• Get the possible conformations for
yGC-RNTs using molecular
mechanics (MM) and molecular
dynamics (MD) simulations
• Analyze energies using
Macromodel (Schrodinger MM
package) and 3D-RISM theory
A
As s ociation Free Energy
(kcal/ mol) Th o u san d s
TheyGC wasdesignedsothatanRNT
withalarge channelcouldformand
accommodateahostmoleculeinits
cavitythatisbetween19-26Å in
diameter.
6-memberedand7-memberedRNTsweremodeledusingmolecular
mechanicaltechniquesandbothwerefoundtobeprobableconfigurations.
EnergeticsanalysispredictsthatformationofRNTsfromavailablemotifsin
solutiongoesthroughamotifbymotifadditionandisspontaneousat300K.
Experimentsare currentlybeingdonetoverifythestructureoftheRNTs.
C
Figure 1. yGC motif (A), rosette
formed by 6 yGC motifs (B), and a
twenty-ring-stack RNT, hydrogen
atoms are hidden for clarity (C).
Suggested References
1. J. Am. Chem. Soc. 2001, 123 (16), 3854.
2. ChemPhysChem, 2010, 11, pp 361-367