Nanodiamond

mechanical properties and chemistry

George Schatz

Outline:1.

Nanodiamonds

in drug delivery

2.

Ultrananocrystalline

diamond

Molecular Simulation of Nano-diamond Assisted Delivery of Anti-Cancer Drug Doxorubicin

NSF Summer Institute on Nanomechanics, Nanomaterials and Micro/Nanomanufacturing

Northwestern University, Evanston Illinois 60201

May 27th, 2009

Prof. George Schatz

Department of Chemistry, Northwestern University

Diamond

Great Star of Africa, 1915largest rough diamond ever found

530 carats ( 100 grams), 76 facets

58.9 x 54.4 x 27.7 mm

estimated value: $400 million

Crystal Structure of Diamond

8-atom Face-Centered Cubic (FCC) Lattice

predominantly composed of SP3 carbonexcept for SP2 carbon on surface

high density 3.5 g/cm3

Nanodiamond

TEM picture of nanodiamond

particle size: 2 ~ 20 nm

extremely large relative surface area

spontaneous water absorption even at ambient condition

micrometer self-aggregate easily formed

The first successful synthesis was made in 1963

structure of nanodiamond has NOT been well characterized

How nanodiamond was made?

Trinitrotoluene (TNT)

+

Hexogen (RDX)

detonation

yield rate, composition, shape and size sensitive to the reaction condition,particular the cooling capability of reaction chamber

Nanodiamond extracted from combustion soot

Surface Functionalization of Nanodiamond

-OH, -NH2, -CN, -Me, -NCO, -COOH, -COOMe, -COCl, -TMS, -OTS, -Cl, -Br-tBu, -C6, -C18, -C8F17, -Vinyl, -Acrylate, -PEG, -Ph, -PhF5, -APTES, -Bz, -TIPS

Largely available functional groups:

Extension of functionalization can be measured by spectroscopy techniques, including

Fourier Transform Infrared Spectroscopy (FTIR), Raman Spectroscopy and Fluorescence

Besides traditional oxidation-reduction chemical methods, ultra-fast functionalization can be accomplished in minutes using cool plasma tecnique

Functionalized nanodiamonds typically have significantly improved solubility

Emerging Applications of NanodiamondMotor engine lubricant: 8% more MPG realized.

Biochip for protein separation, purification and detection.

toxity-free delivery of anti-cancer drug Doxorubicin

Nanodiamond-embedded microfile devices for localized chemotherapeutic elution.R. Lam, M. Chen, E. Pierstorff, H. Huang, E. Osawa and D. Ho. ACS Nano, 2008, 2, 2095

Likely Structures of Nanodiamond

(a) octahedral (b) truncated octahedral (c) cuboctahedral

(d) cuboid

shapes

Crystallinity and surface electrostatics of diamond nanocrystal. A.S. Banard and M. Sternberg. J. Mater. Chem. 2007, 17, 4811.

Optimized by Tight-Binding DFT

Anti-cancer Drug Doxorubicin

Amphiphilichydrophobic aromatic site

hydrophilic sugar site conjugated aggregates observed

DNA duplex intercalated by Doxorubicin

pKa 8.4

Ratio of SP2/SP3 Carbon atoms on reconstructed nanodiamond surface

Surface is largely composed of SP2 type carbon atoms

A handful of SP3 atoms are stillrequired for shape maintenance

π-conjugation is expected at SP2-rich domains.

Cuboctahedral (660)

Rather large solvent accessible area

SAA: 1963 Å2

Volume: 2664 Å3SP2SP3

Surface Electrostatic Potential

Upon hydrogenation, the nanodiamond surface becomes more electropositive.

bare hydrogenated

Technical Details of SimulationsDFT Calculations:

XC Functional: Perdew-Burke-Ernzehor (PBE)Norm-conserving Pseudopotential: Goedecker-Teter-Hutter (GTH)Basis Set: Double-Zeta-Valence-Polarization Gaussian Orbitals (DZVP)Simulation Package: CP2K http://cp2k.berlios.de (GPL license)

MM Force Field Development Protocol:

Amber atom typesIntramolecular and intermolecular parameters derived fromGeneralized Amber Force Field (GAFF)Atomic partial charges fitted to reproduce DFT PES by Restrained ElectroStatic method (RESP) using Amber 9 package

Molecular Dynamics Simulation:

Isothermal-Isobaric Ensemble (NPT) using Gromacs 4 package

Quality of MM force fields

RMSD of MM Optimized Structures with respect to QM: (in Å)

Dipole Moment: (in Debye)

B-C660 H-C660 N-DOX P-DOX

DFT 4.8 1.5 7.3 23.8MM 11.2 9.1 7.3 27.9Please note: a single NaCl possesses a dipole of 9.0 Debye

B-C660 H-C660 N-DOX P-DOX

RMSD 0.01 0.01 0.1 0.2

Binding Energy of Protonated Doxorubicin to Bare and Hydrogenated Nanodiamond

EBinding EDoxND EDox END

Hydrogenation notably decreases binding affinity due to weaker π-stacking

-77.2 kcal/mol -64.5 kcal/mol

pH-dependent Drug Binding Behavior

high pH low pH

Protonation of Doxorubicin is critical for efficient dispersion and binding(water has been removed)

Binding Patterns

π-stacking type binding

micelle type binding

simultaneous binding

Radial Distribution Functions of protonated Dox with respect to ND

Strong binding indicated by the high first peak at 1.2 nm

Binding Free Energy Profiles

Ultrananocrystalline (UNCD) Diamond Films

D. M. Gruen

et al, Appl. Phys. Lett. 64 (1994) 1502: J. Vac. Sci. Tech. A13 (1995) 1628.

Ar/CH4

/N2

-plasma UNCD

•

16 nm diamond grains.

•

2 nm-wide grain boundaries.

•

~50 % sp2

carbon at

the GB’s.•

Electrically conductive

S. Bhattacharyya et al., Appl. Phys. Lett. 79, 1441 (2001).

Σ13 grain boundary structure67.4o

twist perpendicular to 100 plane208 atoms

P. Zapol, M. Sternberg, L. A. Curtiss, T. Frauenheim, D. M. Gruen, Phys. Rev. B 65, 045403 (2002)

DF-TB

(tight binding) studies of diamond film growth, and of grain boundary structures.

UNCD Structural Modeling

Fracture of UNCD grain boundaries

no GB two GBs

UNCD grain boundary fracture: PBE Calculations

•

Significant damage to both GB’s.

•

Complete failure of the bottom GB.

Mechanical properties: UNCD Grain Boundary Fracture

E

-

the Young’s modulus (stiffness).f

-

failure strainf

-

fracture stress.

Jeffrey T. Paci, Ted Belytschko

and George C. Schatz, Chem. Phys. Lett., 414(4-6), 351-358 (2005).

Σ13

Grain Boundary Structure

Single crystal diamond

DFT-PBE Results

Theoretical versus practical strengths

•

Our E values of 1.09 and 1.05 TPa

for single-crystal and UNC diamond, respectively, agree well with the corresponding experimental values of 1.05 and 0.95 TPa.

•

Experimentally measured fracture stress values for single-crystal diamond and UNCD are f

~ 4 GPa

and f~ 1-5 GPa, respectively. We are way-off here. What we have left out is the effect of large (~100 nm) cracks.

•

Cracks lead to regions of stress concentration which result in crack propagation and material failure.

•

The effect of defects on the fracture behavior of a brittle material like diamond can be described using Griffith theory.

Plasma-nitrogen UNCD

•

197 atom cluster based on Σ

13

structure. •

~1nm-wide GB layer.

•

50% sp2, 50% sp3

(close to experiment).

Plasma Nitrogen Results

Decrease in E

and σf

but values still large.

J. Paci, T. Belytschko, G. C. Schatz, Phys. Rev. B, 74, 184112 (2006)

UNCD (PBE) 1.05 0.13 100Amorphous Carbon GB Structure

Σ13

GB Structure

Theoretical versus measured strengths

•

Calculated E values (1.09 and 1.05 TPa) for single-crystal and UNC diamond, respectively, agree well with the corresponding experimental values of 1.05 and 0.95 TPa.

•

Fracture stress values for single-crystal diamond and UNCD are f

~ 1-5 GPa.

What we have left out is the effect of large (~100 nm) cracks.

•

The effect of defects on the fracture behavior of a brittle material like diamond can be described using Griffith theory.

Griffith theory (1920)

•

Basic idea: when the strain energy released by fracture is larger than the energy required to create new surface (the surface energy), a crack will propagate.

•

For a penny-shaped crack of radius c,

the Griffith fracture stress is

where

is the fracture surface energy and

is the Poisson ratio

Practical strength of UNCD•

Typical experimentally observed cracks have radii, c ~ 300 nm.

•

We calculate =2.6 J/m2. So Griffith predicts f

= 3.8 GPa, a value within the f

~ 1-5 GPa

UNCD fracture stress range.

•

Similar argument works for N-doped UNCD.

H. D. Espinosa et al., J. Appl. Phys. 94, 6076 (2003).

Future directions: Nanodiamond research

Effect of nanodiamond size and shape on Doxorubicin bindingInfluence of cosolute concentration and pH environment

Determination of optimal functionalization sites

Optical behavior of fluorescent functionalized nanodiamond

Mechanical property of nanodiamond-polymer composite coating

Charge conduction in doped-nanodiamond based Micro Electro- Mechanical Systems

Automation of molecular model development for nanodiamond

Drug delivery applications:

Diamond films:

Theory:

Models for defect structures