RIGHT AND LEFT:RIGHT AND LEFT:

Geochemical OriginsGeochemical Origins

Of Life’s HomochiralityOf Life’s Homochirality

RIGHT AND LEFT:RIGHT AND LEFT:

Geochemical OriginsGeochemical Origins

Of Life’s HomochiralityOf Life’s HomochiralityUnited States Naval ObservatoryUnited States Naval Observatory

February 28, 2008February 28, 2008Robert Hazen, Geophysical LaboratoryRobert Hazen, Geophysical Laboratory

Research CollaboratorsResearch CollaboratorsResearch CollaboratorsResearch CollaboratorsCarnegie Institution Hugh Churchill H. James Cleaves George Cody Gözen Ertem Tim Filley Rebecca Martin Jake Maule Andrew SteeleGeorge Washington Univ. Glenn Goodfriend Henry TengUniv. of Delaware Donald Sparks

Univ. of Arizona Robert T. DownsGeorge Mason University Harold MorowitzJohns Hopkins University Dimitri Sverjensky Caroline Jonsson Christopher Jonsson Carnegie-Mellon University Aravind Asthagiri David ShollSmithsonian Institution Ed VicenziSpanish Astrobiology Inst. Antonio Salgado-Serrano

Two QuestionsTwo Questions(Possibly Related)(Possibly Related)

Two QuestionsTwo Questions(Possibly Related)(Possibly Related)

2. What processes selected life’s idiosyncratic molecules?

1. How do crystals interact with organic molecules?

Crystal-Molecule InteractionsCrystal-Molecule InteractionsCrystal-Molecule InteractionsCrystal-Molecule Interactions

• Formation of teeth and bones

• Biomineralization and biofilms

• Fossilization

• Weathering and soil formation

• Paints, glues, dyes

• Environmental monitoring and clean-up

• Nanotechnology

• Drug synthesis and purification

• Origins of life

Crystal-Molecule InteractionsCrystal-Molecule InteractionsCrystal-Molecule InteractionsCrystal-Molecule Interactions

Huong et al. (2003) “Bone recognition mechanism ofHuong et al. (2003) “Bone recognition mechanism ofporcine osteocalcin from crystal structure” Nature 425:977-980.porcine osteocalcin from crystal structure” Nature 425:977-980.

Central Assumptions ofCentral Assumptions ofOrigin-of-Life ResearchOrigin-of-Life ResearchCentral Assumptions ofCentral Assumptions ofOrigin-of-Life ResearchOrigin-of-Life Research

The first life forms were carbon-based.

Life’s origin was a chemical process that relied on water, air, and rock.

The origin of life required a sequence of emergent steps of increasing complexity.

Life’s Origins:Life’s Origins:Four Emergent StepsFour Emergent Steps

Life’s Origins:Life’s Origins:Four Emergent StepsFour Emergent Steps

1. Emergence of biomolecules

2. Emergence of organized molecular systems

3. Emergence of self-replicating molecular systems

4. Emergence of natural selection

Origin of Biomolecules: The Problem

Origin of Biomolecules: The Problem

A fundamental attribute of life is a high degree of molecular selectivity and organization, but prebiotic synthesis processes are indiscriminate.

What prebiotic processes might have contributed to such selection and organization?

Biomolecular Selectivity:Biomolecular Selectivity:Amino AcidsAmino Acids

Biomolecular Selectivity:Biomolecular Selectivity:Amino AcidsAmino Acids

• Only 20 biological amino Only 20 biological amino acids compared to >90 in acids compared to >90 in Murchison meteoriteMurchison meteorite

• Only Only -H amino acids (i.e., -H amino acids (i.e., no no -methyl amino acids) -methyl amino acids)

• Homochirality – L>>RHomochirality – L>>R

Biological HomochiralityBiological HomochiralityBiological HomochiralityBiological HomochiralityMany of life’s essential molecules are chiral.Many of life’s essential molecules are chiral.

42

C

3

1

(L)-enantiomer(L)-enantiomer

42

C

3

1

(R)-enantiomer(R)-enantiomer

How did life on Earth become homochiral?How did life on Earth become homochiral?

Annual sales of chiral pharmaceuticals Annual sales of chiral pharmaceuticals approaches $200 billion.approaches $200 billion.

Basic VocabularyBasic VocabularyBasic VocabularyBasic Vocabulary

Chiral = Enantiomeric = HandedChiral = Enantiomeric = Handed

“ “D” = “R” = Right-handedD” = “R” = Right-handed

“ “L” = “S” = Left-handedL” = “S” = Left-handed

Homochiral versus heterochiralHomochiral versus heterochiral

Racemic = mixture of left and rightRacemic = mixture of left and right

Symmetry Breaking = separate D/LSymmetry Breaking = separate D/L

Chiral Purity is ImportantChiral Purity is ImportantChiral Purity is ImportantChiral Purity is Important

Smells like orangesSmells like oranges Smells like lemonsSmells like lemons

R-Limonene Mirror L-LimoneneR-Limonene Mirror L-Limonene

Chiral Purity is ImportantChiral Purity is ImportantChiral Purity is ImportantChiral Purity is Important

N

O

O

HN

H N

O

O

NH

H

R-enantiomer

Analgesic (Good)

S-enantiomer

Teratogen (Bad)

ThalidomideThalidomide

Chiral Purity is ImportantChiral Purity is ImportantChiral Purity is ImportantChiral Purity is Important

N

O

O

HN

H N

O

O

NH

H

R-enantiomer

Analgesic (Good)

S-enantiomer

Teratogen (Bad)

ThalidomideThalidomide

Enantioselective ChemistryEnantioselective ChemistryEnantioselective ChemistryEnantioselective Chemistry

2. Enantioselective synthesis

Chiral catalystProchiral Reactants

Enantiomerically PureProducts

1. Enantioselective separation

Chiral reagentRacemic Mixture

Enantiomerically PureProduct

Prebiotic Chiral SelectionPrebiotic Chiral SelectionPrebiotic Chiral SelectionPrebiotic Chiral Selection

• But life demonstrates a remarkable But life demonstrates a remarkable

degree of chiral selectivity.degree of chiral selectivity.

• Prebiotic synthesis processes produce Prebiotic synthesis processes produce

mixtures of left and right molecules.mixtures of left and right molecules.

What is the mechanism of What is the mechanism of

symmetry breaking?symmetry breaking?

Previous HypothesesPrevious HypothesesPrevious HypothesesPrevious Hypotheses

Global Mechanisms:

• Selective synthesis or photolysis by CPR

• Parity violations in ß decay

Local Chiral Microenvironments:

• Chiral molecules, themselves

• Mineral surfaces

Our Hypothesis: Minerals WorkOur Hypothesis: Minerals WorkOur Hypothesis: Minerals WorkOur Hypothesis: Minerals Work

Our Hypothesis: Minerals WorkOur Hypothesis: Minerals WorkOur Hypothesis: Minerals WorkOur Hypothesis: Minerals Work

Aspartic acid on calcite

Lysine on quartz

TCA on calcite

TCA on feldspar

ObjectivesObjectivesObjectivesObjectives

1. Examine the occurrence of chiral mineral surfaces in nature (Hazen 2004; Downs & Hazen 2004).

2. Demonstrate chiral selectivity by mineral surfaces (Hazen et al. 2001; Castro-Puyana et al. 2008).

3. Deduce mineral-molecule interactions (Asthagiri &

Hazen 2006; 2007).

4. Propose a general experimental research strategy (Hazen, Steele et al. 2005; Hazen 2006).

1. Natural Chiral Surfaces1. Natural Chiral Surfaces1. Natural Chiral Surfaces1. Natural Chiral Surfaces

Crystal terminationCrystal termination

Stepped surfaceStepped surface

Kink siteKink site

FCC(643) 346FCC

Chiral Single-Crystal Metal Surfaces

Mirror images are non-superimposable

Chiral Surfaces Can SelectChiral Molecules

Chiral Surfaces Can SelectChiral Molecules

McFadden et al. (1996) “Adsorption of chiral alcohols on ‘chiral’ metal surfaces.” Langmuir 12, 2483-2487.

Chiral AdsorptionChiral Adsorption

Quartz – SiO2Quartz – SiO2

Quartz is the only common chiral rock-forming mineral

Right Left

Reports of successful chiral selections as early as the 1930s.

Yet all previous authors used powdered quartz!

Quartz: Face-Specific AdsorptionQuartz: Face-Specific Adsorption

(10-11)

(01-11)

Quartz Crystal FacesQuartz Crystal Faces

Courtesy of S. ParkerCourtesy of S. Parker

Quartz – (100) FaceQuartz – (100) Face

Quartz – (101) FaceQuartz – (101) FaceQuartz – (101) FaceQuartz – (101) Face

MIRRORMIRROR

Quartz – (011) FaceQuartz – (011) FaceQuartz – (011) FaceQuartz – (011) Face

Feldspar (110)Feldspar (110)Feldspar (110)Feldspar (110)

Feldspar (110)Feldspar (110)Feldspar (110)Feldspar (110)

Diopside – (110) FaceDiopside – (110) FaceDiopside – (110) FaceDiopside – (110) Face

Diopside – (110) FaceDiopside – (110) FaceDiopside – (110) FaceDiopside – (110) Face

Calcite – CaCOCalcite – CaCO33Calcite – CaCOCalcite – CaCO33

Calcite – (214) FaceCalcite – (214) FaceCalcite – (214) FaceCalcite – (214) Face

Chiral Indices: Calcite (104)Chiral Indices: Calcite (104)Chiral Indices: Calcite (104)Chiral Indices: Calcite (104)

Chiral Indices: Calcite (214)Chiral Indices: Calcite (214)Chiral Indices: Calcite (214)Chiral Indices: Calcite (214)

Table of Chiral IndicesTable of Chiral IndicesMineral Face Average Displ. Max. Displ.

Calcite (214) 0.93 1.81

Diopside (110)-c 0.53 0.85(110)-e 0.72 1.54

Copper (854) 0.84 1.29

Feldspar (110) 0.52 1.01

Quartz (100) 0.54 0.59(011) 0.36 0.46(101) 0 0

Downs & Hazen (2004) J. Molec. Catal.

Table of Chiral IndicesTable of Chiral Indices

Mineral Face Average Displ. Max. Displ.

Calcite (214) 0.93 1.81

Diopside (110)-c 0.53 0.85(110)-e 0.72 1.54

Copper (854) 0.84 1.29

Feldspar (110) 0.52 1.01

Quartz (100) 0.54 0.59(011) 0.36 0.46(101) 0 0

Table of Chiral IndicesTable of Chiral Indices

Mineral Face Average Displ. Max. Displ.

Calcite (214) 0.93 1.81

Diopside (110)-c 0.53 0.85(110)-e 0.72 1.54

Copper (854) 0.84 1.29

Feldspar (110) 0.52 1.01

Quartz (100) 0.54 0.59(011) 0.36 0.46(101) 0 0

Conclusions 1: Chiral SurfacesConclusions 1: Chiral SurfacesConclusions 1: Chiral SurfacesConclusions 1: Chiral Surfaces

Chiral mineral surfaces are common. hiral mineral surfaces are common.

In oxides and silicates, larger chiral In oxides and silicates, larger chiral indices are often associated with the indices are often associated with the presence of both terminal cations and presence of both terminal cations and anions. anions.

Relatively large chiral indices are Relatively large chiral indices are often associated with stepped and often associated with stepped and kinked surfaces.kinked surfaces.

Glenn Goodfriend with Steve GouldGlenn Goodfriend with Steve Gould

2. Mineral Chiral Selection2. Mineral Chiral Selection2. Mineral Chiral Selection2. Mineral Chiral Selection

Selective Adsorption on CalciteSelective Adsorption on CalciteSelective Adsorption on CalciteSelective Adsorption on Calcite

•CaCOCaCO33

•RhombohedralRhombohedral

•Common (214) formCommon (214) form

GC AnalysisGC Analysis GC AnalysisGC Analysis

Aspartic acid doubletAspartic acid doublet

GC AnalysisGC AnalysisGC AnalysisGC Analysis

Aspartic acid doubletAspartic acid doublet

~15 secondsSeparation

Chiral Selection on CalciteChiral Selection on CalciteChiral Selection on CalciteChiral Selection on Calcite

D excess D excess

L excess L excess

Hazen et al. (2001) Hazen et al. (2001) PNASPNAS

Calcite (214) crystal surfaces select D- and L-aspartic acid.

We do not observe selective adsorption of glutamic acid or alanine on calcite.

Maximum selective adsorption occurs on terraced crystal faces. This fact suggests that chiral selection may occur along linear features.

The alignment of chiral amino acids on calcite may lead to homochiral polymerization.

Conclusions 2:Conclusions 2:Mineral Chiral SelectionMineral Chiral Selection

Conclusions 2:Conclusions 2:Mineral Chiral SelectionMineral Chiral Selection

3. Modeling Mineral-Molecule 3. Modeling Mineral-Molecule InteractionsInteractions

3. Modeling Mineral-Molecule 3. Modeling Mineral-Molecule InteractionsInteractions

Why do D- and L-amino acids bind differently Why do D- and L-amino acids bind differently (aspartic acid versus alanine on calcite)?(aspartic acid versus alanine on calcite)?

Experiments do not tell us much except that Experiments do not tell us much except that there may be an electrostatic contribution.there may be an electrostatic contribution.

Can modeling shed light on specific atomic-Can modeling shed light on specific atomic-scale interactions?scale interactions?

Modeling Mineral-Molecule Modeling Mineral-Molecule InteractionsInteractions

Modeling Mineral-Molecule Modeling Mineral-Molecule InteractionsInteractions

D-Alanine onD-Alanine on

Calcite (214)Calcite (214)

Modeling Alanine on Calcite (214)Modeling Alanine on Calcite (214)Modeling Alanine on Calcite (214)Modeling Alanine on Calcite (214)

Use density functional theory (an accurate 1st

principles method) to model interactions.

As a first approximation ignore water (i.e., gas phase model).

Examine numerous plausible configurations.

The most stable configurations involve Ca-O bonding between calcite and carboxyl groups.

D-Alanine-Calcite (214) InteractionsD-Alanine-Calcite (214) InteractionsD-Alanine-Calcite (214) InteractionsD-Alanine-Calcite (214) Interactions

Begin by bringing a D-alanine molecule close to an unrelaxed calcite surface.

initial final H

N

C

O

Ca

initial final H

N

C

O

Ca

D-Alanine-Calcite (214) InteractionsD-Alanine-Calcite (214) InteractionsD-Alanine-Calcite (214) InteractionsD-Alanine-Calcite (214) Interactions

The stable converged configuration reveals surface relaxation and Ca-O and O-H

interactions, but no strong third interaction.

initial final H

N

C

O

Ca

initial final H

N

C

O

Ca

Alanine-Calcite (214) InteractionsAlanine-Calcite (214) InteractionsAlanine-Calcite (214) InteractionsAlanine-Calcite (214) Interactions

D-alanineD-alanine L-alanineL-alanine

(D)-ASP (L)-ASP

The most stable configuration found for D- and L-The most stable configuration found for D- and L-aspartic acid on calcite (214) surface. The D aspartic acid on calcite (214) surface. The D

enantiomer is favored by 8 Kcal/mol. enantiomer is favored by 8 Kcal/mol.

Aspartic Acid-Calcite (214) Aspartic Acid-Calcite (214) InteractionsInteractions

Aspartic Acid-Calcite (214) Aspartic Acid-Calcite (214) InteractionsInteractions

Conclusions 3: Modeling Conclusions 3: Modeling Mineral-Molecule InteractionsMineral-Molecule Interactions

Conclusions 3: Modeling Conclusions 3: Modeling Mineral-Molecule InteractionsMineral-Molecule Interactions

Chiral interactions require Chiral interactions require three points of interaction.three points of interaction.

Which molecule sticks to Which molecule sticks to which surface is idiosyncratic.which surface is idiosyncratic.

4. A General Research Strategy4. A General Research Strategy4. A General Research Strategy4. A General Research Strategy

How do we evaluate interactions among

the numerous possible mineral-molecule

pairs?

We need a combinatoric approach.

Jake Maule, Andrew Steele and Rebecca Martin

A Combinatoric StrategyA Combinatoric StrategyA Combinatoric StrategyA Combinatoric Strategy

ChipWriter

• Up to 126 minerals

• Up to 49,152 spots per

mineral

• Up to 96 different wells

• 100-micron spots

A B CMicroarrays of Cy3-labeled asparagine, glutamine

and tyrosine on glass at 20 serial dilutions.

Each microarray was scanned simultaneously with 532nm/635nm lasers and the fluorescence emission was captured at the wavelength bands of 557-592nm

(Cy3) and 650-690nm (Cy5). Each image shows the intensity of Cy3/Cy5 fluorescent bands at a focal distance of 60m (left) and 120m (right).

Microarrays of Cy3-labeled L-lysine on left- and right-handed quartz (100) faces at 8 serial dilutions. 150-micron spots.

A B

Edward Vicenzi and Detlef RostToF-SIMS Lab, Smithsonian Institution

ToF-SIMS

High-resolution ion fragment maps of

150-micron L-lysine spots on calcite (214).

X

X

mass / u42.85 42.90 42.95 43.00 43.05 43.10 43.15

010

110

210

310

410

510

Inte

nsity

mass / u20 40 60 80 100 120 140 160 180 200 220 240 260 280

010

110

210

310

410

510

610

710

Inte

nsity

43Ca+ 42CaH+

C2H3O+

C2H5N+

C3H7+

L lysinecalcite

m/m ~ 8000 FWHM

300 AMU L-Lysine on Calcite (214)

9 x 13 Array on 1 x 1 x 0.3 cm feldspar plate.

AMINO ACIDS AND SUGARS ON FELDSPAR(010) Face – 1 x 1 cm plate

Feldspar (010) in ToF-SIMS Sample Holder

D-Lysine on Feldspar (010)

DL-Xylose on Feldspar (010)

mass / u42.85 42.90 42.95 43.00 43.05 43.10 43.15 43.20

010

110

210

310

410

510

Inte

nsi

ty

C2H5N (43.04)

C2H3O (43.02)

Key to Adsorbants----- arabinose

----- lyxose

----- ribose

----- xylose

----- lysine

Mass vs. Intensity for ~43 mass unit fragments

PentoseSugars

Amino Acid

CONCLUSIONSCONCLUSIONS

• Microarray technology coupled with ToF-SIMS provides a powerful experimental means for combinatoric studies of mineral-molecule interactions.

• Many mineral surfaces have the potential for chiral selection of plausible prebiotic molecules.

With thanks to:

NASA Astrobiology Institute National Science Foundation

Carnegie Institution of Washington