The chemistry of life’origins: II. From the building blocks to life

CHONS + H 2 O  Robots or catalysts  RNA world Viruses?  Cells, i.e. RNA proteins membranes Clays? 

Polymer formation in water Formally, the formation of a biopolymer consists to eliminate water molecules between monomer units. However, the formation of either polyamino acids or polynucleotides from their monomers is not energetically favored. In water, energy is required to link 2 amino acids. For example, the free energy for the condensation of alanine and glycine to form the dipeptide alanyl-glycine in water is 4.13 Kcal/mol at 37°C and pH 7: H-Ala-OH + H-Gly-OH  H-Ala-Gly-OH + H 2 O  G 0 = 4.13 Kcal The thermodynamic barrier is very large for the formation of a long chain polyamino acid. For example, 1 M solutions in each of the 20 protein amino acids would yield at equilibrium a M concentration for a Dalton protein. To yield one protein at equilibrium, the volume of the solution would have to be times the volume of the Earth! So energy input was necessary to make polynucleotides and polyamino acids in the primitive oceans.

AlanineNCA

Glu-SEt Glu-SET & bicarbonate Glu-oligomers obtained in the presence of bicarbonate via the intermediate formation of a carbamate – OOC-NH-CHR-CO-SET and probably a Leuch’s anhydride.

ZnS FeS CdS Clay Blank 4-SEt4-OH3-SEt3-OH2-SEt2-OHDKP1-SEt Polymerization of H-Leu-SEt in the presence of different mineral surfaces (15 days, pH 8, 25 C) Polymerization of H-Leu-SEt in the presence of different mineral surfaces (15 days, pH 8, 25 C) n H–Leu–S–C 2 H 5  H–Leu n –S–C 2 H 5 + nHS–C 2 H 5 H–Leu n –S–C 2 H 5 + H 2 O  H–Leu n –OH + HS–C 2 H 5

Wet/dry C 7-OH6-OH5-OH4-OH3-OH2-SEt2-OHDKP1-SEt Polymerization of H-Leu-SEt in the presence of CdS using wet/dry cycles (12 hr at 25 C / 12 hr at 80 C for 2 weeks, pH 8).

Rainbow submarine hydrothermal system

n H–Leu–S–C 2 H 5  H–Leu n –S–C 2 H 5 + nHS–C 2 H 5 H–Leu n –S–C 2 H 5 + H 2 O  H–Leu n –OH + HS–C 2 H 5 Polymerization of amino thioesters on hydrothermal sediments control 1 2 DKP 3 4 >4

Flow reactor simulating a submarine hydrothermal system

The β-sheet structure of alternating hydrophilic / hydrophobic peptides

Formation of double layer β-sheets of alternating hydrophobic/hydrophilic polypeptides, driven by hydrophobic clustering of side-chains.

β-sheets are more stable than α-helices

The hydrophobic amino acid must be strongly hydrophobic

Poly(Leu 50, Lys 50 ) which exhibits random coil, α- and β-geometries, develops more β-structures with increasing temperature. 20 °C60 °C α 58%34% β 27%51% random16%15% Higher temperatures favor β-sheet structures

The β-sheet structure of alternating hydrophilic / hydrophobic peptides

Percentage of β-sheets with increasing L-enantiomers

77%L  84%L 86%L  92%L 95%L  99%L

The alternating polypeptide poly(Glu- Leu) is randomly coiled in water. It adopts: -a β-sheet structure in the presence of traces of CaCl 2 but - an α–helix in the presence of FeCl 3.

Even more interestingly, poly(Glu-Leu) is also capable of extracting cations from insoluble minerals and adopts an ordered conformation: -a β-sheet structure in the presence of CdS - an α–helix in the presence of molybdenum Peptides with 10-amino acids are long enough to significantly adsorb onto the mineral surface. Montmorillonite adsorbs the peptide but does not induce any conformational change.

Control + poly(Leu-Lys) Poly(Leu-Lys) catalyses the cleavage of RNA phosphodiester bonds, providing a rate enhancement of 185, compared to the control. The decapeptide is long enough to exhibit the catalytic activity. Poly(Pro-Leu-Lys-Leu-Lys) and poly(D,L Leu - D,L Lys) are inactive (rate enhancement of 11 and 17, resp.).

CONCLUSION Stable short β-sheet forming peptides were probably abundant in the primitive oceans Doing what?

CHONS + H 2 O  Robots or catalysts  RNA world Viruses?  Cells, i.e. RNA proteins membranes

Heterocyclic base (adenine) Sugar (ribose) Phosphate A nucleotide, the basic constituent of RNA

RNA ribose (peak 8) is poorly formed from formaldehyde

Chemical self-replication works beautifully with preformed RNA strands

Are clays of any help?

With CDI

RNA Pyranosyl-RNA, p-RNA P-RNA: base pairs more strongly than RNA the twist of the helices is less important self-organisation and stereoselective polymerisation of p-ATCG tetramers

RNA Threose-RNA, TNA TNA: is more stable to hydrolysis than RNA forms TNA-TNA double helices forms TNA-RNA hybrid duplexes with RNA

Peptide nucleic acid, PNA PNA: has a 2-aminoethyl glycine backbone forms PNA-PNA double helices forms PNA-RNA hybrid double helices

CHONS + H 2 O  Robots or catalysts  RNA world Viruses?  Cells, i.e. RNA proteins membranes

Catalysis Autocatalysis Self-replication: autocatalysis + selection of bifunctional elements

Autocatalytic growth of micelles: primitive life?

A self-replicating peptide? Reza Ghadiri showed that the 32-residue α-helical peptide autocatalytically templates its own synthesis by accelerating the amide bond condensation of 15- and 17-residue fragments. The 32-residue peptide replicator is capable of efficiently amplifying homochiral products from a racemic mixture of peptides fragments

Catalysis Autocatalysis Self-replication: autocatalysis + selection of bifunctional elements

Cross-inhibition in template-directed polymerisation of activated L,D nucleotides

Autocatalytic growth of Glu-oligomers on short α-helices with an active ester of Glu in benzene

Autocatalytic growth of Glu-oligomers on short α-helices

Catalysis Autocatalysis Self-replication: autocatalysis + selection of bifunctional elements

Possible steps ahead

Self-replication by surface-controlled growth and fracture

That’s all for today, folks!

Stereoselection via glycine crystals

Magnetochirality (with 7.5 Tesla!)