Proceedings of the 2nd WSEAS International Conference on BIOMEDICAL ELECTRONICS and BIOMEDICAL INFORMATICS

A Prebiotic Photochemical Synthesis of Glycerides

N. Aylward , Queensland University of Technology, Brisbane,Australia [email protected]

Abstract: - The magnesium ion metalloporphyrin complex is shown to bind the ligands alkyne and carbon monoxide with migration and bridging between the metal ion and nitrogen bound ligands. The sequence of reactions to form the glyceride acyl bond is: 1. Up to four carbon monoxide molecules may be individually bound to the metal and migrate to the four vacant nitrogen sites to form bridged aziridine-2one rings. 2. The metal bound alkyne (e.g. propyne) reacts with a peripherally bound carbon monoxide to form a propanone ring compound. 3. The propanone ring ligand isomerises by a hydrogen shift to a 3-methyl butenone ligand with an activation energy of 0.112 h. 4. The 3-methyl butenone ligand forms an acyl bridge to a peripheral carbon monoxide with an activation energy of 0.007 h. 5. The excited state complex is greatly stabilised by protonation, whilst mild hydrogenation at the metal and positively charged carbon atom frees the alkene ester. 6. The activation energy to bond the three carbon monoxide entities bound to the peripheral nitrogen sites is 0.126 h. 7. Mild reduction at the peripheral nitrogen sites frees the mono-glyceride. The reactions have been shown to be feasible from the overall enthalpy changes in the ZKE approximation at the HF and MP2 /6-31G* level.

Key-Words: - Prebiotic photochemical synthesis, mono-glycerides, carbon monoxide, propyne.

1 Introduction From a prebiotic perspective [5,6] it is desirable if Glycerol is present in nature esterified on the these molecules formed spontaneously from a hydroxyl groups by fatty acids as mono-, di-, or tri supposed prebiotic atmosphere to be inevitably acyl glycerides [1,2,3]. These glycerides serve present as micellular walls of rudimentary cells. It primarily to store fuel in the form of fat droplets in has been often held that the atmosphere of the Earth cells. The phosphoglycerides contain two fatty acid was originally mildly reducing [1,7] implying the molecules esterified to the two free hydroxyl groups presence of concentrations of carbon monoxide and of glycerol-3-phosphate and an alcohol esterified to formaldehyde [8], the partially reduced substrates of the phosphoric acid. They occur mainly in modern photosynthesis. It has also been membranes as phosphatidyl ethanolamine and demonstrated that porphin may act as a catalyst for phosphatidyl choline. The polarity of their head the formation of sugars [9] and polyenes [10]. groups enables them to spontaneously form This paper proposes a model for the catalytic micelles, monolayers and bi-layers. They are formation of ester linkages between a nascent considered major building blocks of membrane glycerol backbone and a preformed alkyne side- structures such as the liquid-crystalline chain which has some resemblance to modern phosphoglyceride bilayer where they are present as photosynthesis in that the catalyst proposed is a 40-50 % lipid [4]. Naturally occurring triacyl metal porphin [5]. The reactions described have glycerols are by convention named as if they were been deduced as kinetically and thermodynamically derived from L-glyceraldehyde [1]. viable, but photochemical excitation is required to form the glycerol backbone.

ISSN: 1790-5125 52 ISBN: 978-960-474-110-6 Proceedings of the 2nd WSEAS International Conference on BIOMEDICAL ELECTRONICS and BIOMEDICAL INFORMATICS

identical to that of the excited reactant, but the 2 Problem Formulation excitation energy is more than the activation energy The computations tabulated in this paper used the for the transformation [9]. GAUSSIAN98 [11] commercial package. The standard calculations at the HF and MP2 levels This process of binding a carbon monoxide including zero-point energy corrections [12], molecule to the magnesium ion and then migrating together with scaling [13], using the same basis set, the CO group to the periphery may be repeated, 6-31G*. are as previously published [5]. Enthalpy changes at the MP2 level not including scaled zero Mg.porphin.CO + CO → Mg.CO.porphin.CO [3] point energies are designated as ΔH(MP2). The charge (4) transfer complexes are less stable when calculated at Δ H(MP2/6-31g*) = -0.06600 h the Hartree Fock level [12]. If the combined energy of the products is less than Mg.CO.porphin.CO → Mg.porphin.2CO [4] the combined energy of the reactants it may show (5) that the reaction is also likely to be spontaneous at higher temperatures. This paper uses the atomic unit Δ H(MP2/6-31g*) = -0.07007 h of energy, the hartree [11]. 1h = 627.5095 kcal.mol-1. Either of these complexes may form carbon-carbon 1h = 4.3597482 x 10-18 J bonds to give bidentate groups. However, the higher energy complex is that in which both CO groups occupy peripheral ring positions and are 3 Problem Solution bonded, indicated as Mg.porphin.(CO-)2. 3.1 Total Energies (hartrees) The enthalpy change to form the carbon-carbon Carbon monoxide may chelate with the magnesium bond is low as shown, ion of magnesium porphin, which is here taken as a possible catalyst, to form a charge transfer complex Mg.porphin.2CO → Mg.porphin.(CO-)2 [5] where the charge on the ligand is positive and the (6) charge on the porphin molecule is negative. The Δ H = 0.01140 h enthalpy of formation of the complex is small but it appears stable [9]. The activation energy to form the carbon-carbon bond is, 0.126 h, whereas the activation energy to Mg.porphin + CO → Mg.CO.porphin [1] break the bond is 0.032 h, when calculated at the HF (1) (2) level by extending the -CO-CO- bond. A third carbon monoxide group may be added to the third peripheral position by the same mechanism, Δ H = -0.00919 h where the overall reaction is,

If the Mg.porphin (triplet state) is in the triplet state, the enthalpy change is also favourable, as follows: Mg.porphin + 3CO → Mg.porphin.3CO [6] (7) Δ H = 0.28241 h Δ H(MP2/6-31g**) = -0.10388 h

It is postulated that when the complex becomes This complex may easily bond to form a stable excited from photolysis according to the equation, precursor to the glycerol backbone,

Mg.CO.porphin → Mg.porphin.CO [2] Mg.porphin.3CO → Mg.porphin.(CO-)3 [7] (3) (8) Δ H = 0.21892 h Δ H = -0.07935 h the CO group is able to move through a transition The fourth and last available position may be filled state to the porphin ring where it forms an excited, in the same manner to give the highly reactive and but stable bridged aziridine-2one ring [9,14,15] at a unstable quatridentate complex which has gained pyrrole unit. The energy of the product is almost considerable energy from photolysis.

ISSN: 1790-5125 53 ISBN: 978-960-474-110-6 Proceedings of the 2nd WSEAS International Conference on BIOMEDICAL ELECTRONICS and BIOMEDICAL INFORMATICS

-1411.09199 0.31658 Mg.porphin + 4CO → Mg.porphin.4CO [8] (9) Mg.porphin.3CO Δ H = 0.43206 h (7) -1523.93954 0.32395 These high energy compounds may relax to form the Mg.porphin.(CO-)3 more stable van der Waals complexes. (8) The initial reactant for the following reactions is -1524.01717 0.32201 taken to be the reactive, Mg.porphin.4CO, with a Mg.porphin.4CO vacant magnesium ion site for coordination. (9) -1636.80888 0.31847

The data for some of the more stable of these CO -113.02818 0.00484 molecules are given in Table 1, where peripheral carbon monoxide molecules that have fully bonded H2 -1.14414 0.01034 are represented as Mg.porphin.(CO-)n, etc. H- -0.42891 The total energies and zero point energies for the HF ______and MP2/6-31G* equilibrium geometries are given in Table 1. 3.2 The overall stoichiometry for the formation of glycerol 1-butenate.

Table 1 Although Mg.porphin is here taken as the catalyst for the reaction, the overall stoichiometry to form MP2 /6-31G* total energies and zero point energies the glycerol ester, glycerol 1-butenate is as follows, (hartrees) for the respective equilibrium + - geometries 4CO + CH3C≡CH + H + H +3H2 → ______Molecule MP2 ZPE (HF) HOCH2.CH(OH).CH2.O.CO.CH=CH.CH3 [9] hartree hartree glycerol 1-butenate ______(16) Mg.porphin (1) Δ H = -0.79170 h -1185.12250 0.29262 Mg.porphin (triplet, 6-31g**) The enthalpy change is negative indicating that this -1185.10392 may be the energetically favourable route to the initial formation of the ester. The intermediates by Mg.CO.porphin which this stoichiometric reaction may have (2) occurred are as follows: -1298.13452 0.29942 Mg.porphin.CO 3.3 The formation of Mg.1-propen-1-yl. (3) porphin. 4CO -1297.93784 0.30434 The high energy complex Mg.porphin.4CO is Mg.CO.porphin.CO calculated as being stabilised by the coordination of (4) propyne with the metal ion of the complex, as -1411.03187 follows:

Mg.porphin.2CO Mg.porphin.4CO + CH3.C≡C.H → (5) (9) -1411.10194 0.31495 Mg.porphin.(CO-)2 (6)

ISSN: 1790-5125 54 ISBN: 978-960-474-110-6 Proceedings of the 2nd WSEAS International Conference on BIOMEDICAL ELECTRONICS and BIOMEDICAL INFORMATICS

CH (10) 3 -1728.50749 0.39912 C Mg.3-methyl-2-oxo- cyclopropan-1-yl.porphin.3CO CO CO CH (11) -1753.28692 0.38845 Mg.3-methyl-1-oxo-but-1-en-2-yl.porphin.3CO N N (12) CO Mg CO -1753.15882 0.38116

N N Mg.1-propen-1-yl-carboxylate-. porphin. (CO-)3 (13) -1753.28445 0.38491 Mg.1-propen-1-yl-carboxylate-.porphin.CHO.(CO- + )2 Mg.1-propen-1-yl.porphin.4CO [10] (14) (10) -1753.70635 0.40400

Δ H = -0.17227 h Mg.porphin.CH3.CH=CH.CO.CHO.(CO-)2 (15) -1754.56471 0.41350 A model of the optimized complex (9), is shown in Fig.1. glycerol 1-butenate (16) -573.09271 0.20615

Mg.3-methyl-2-oxo- cyclopropan-1-yl.porphin

-1414.39852 0.35955 Mg.3-methyl-1-oxo-but-1-en-2-yl.porphin.

-1414.41750 0.37995

Mg.3-methyl-2-oxo- cyclopropan-1-yl.porphin.CO

-1527.41423 Mg.3-methyl-1-oxo-but-1-en-2-yl.porphin.CO

-1527.40141 Fig.1. The optimized complex Mg.1-propen-1- yl.porphin.4CO

The data for this molecule and the others involved in 3.4 The formation of Mg.3-methyl-2-oxo- the synthesis are given in Table.2. cyclopropan-1-yl.porphin.3CO.

The addition of carbon monoxide to alkynes is a Table 2 classic organic reaction [16], here represented as,

MP2 /6-31G* total energies and zero point energies Mg.1-propen-1-yl.porphin.4CO → (hartrees) for the respective equilibrium (10) geometries ______Molecule MP2 ZPE (HF) hartree hartree ______Mg.1-propen-1-yl.porphin.4CO

ISSN: 1790-5125 55 ISBN: 978-960-474-110-6 Proceedings of the 2nd WSEAS International Conference on BIOMEDICAL ELECTRONICS and BIOMEDICAL INFORMATICS

CH H CH 3 3 C C CO O CO CO CO C C HC CO

N N Mg N N CO

CO Mg N N N N

Mg.3-methyl-1-oxo-but-1-en-2-yl.porphin.3CO Mg.3-methyl-2-oxo- cyclopropan-1-yl.porphin.3CO (12) [12] (11) [11] Δ H = 0.12161 h The potential energy surface is shown in Fig.1. The enthalpy change for the addition of carbon monoxide is favourable. . Δ H = -0.05517 h

The activation energy for the addition reaction of carbon monoxide to a -C≡C- triple bond [5] has been calculated as 0.031 h, and the activation energy to add carbon monoxide to a -C≡N has been given as 0.04 h [17].

Although the Birch reaction is known to be difficult it should be enhanced in this case as the carbon monoxide is already in a high energy complex.

Fig.1. The potential energy surface for the 3.5 The formation of the Mg.3-methyl-1-oxo- prototropic shift on molecule, Mg.3-methyl-2- but-1-en-2-yl.porphin.3CO. oxo- cyclopropan-1-yl.porphin. The X-axis depicts the stretching of the single -C-CO bond, whilst the The critical step in this proposed synthesis is a Y-ordinate depicts the bending angle H-C-C(CH3) prototropic shift and the opening of the three of the cyclopropanone ring. The minimum for the membered 3-methyl cyclopropanone ring to form a cyclopropanone ring is at, X=1.4 A, Y=145 degrees. ketenone. A similar opening of a three membered The saddle points are at X=1.8 A, Y=70 degrees, cyclopropenone ring to give an aldehyde [5] had an and at X=2.3 A, Y=65 degrees. activation energy of 0.083 h. Here, the activation energy to form the cyclopropanone ring was calculated as 0.102 h, whilst the activation energy to open the ring to give the ketenone was calculated as 3.6 The formation of the Mg.1-propen-1-yl- 0.101 h. carboxylate-. porphin. (CO-)3 The reaction does require the input of energy, presumably from photolysis. The ketenyl complex may form a weak ester linkage, Mg.3-methyl-2-oxo- cyclopropan-1-yl.porphin.3CO Mg.3-methyl-1-oxo-but-1-en-2-yl.porphin.3CO (11) → →

ISSN: 1790-5125 56 ISBN: 978-960-474-110-6 Proceedings of the 2nd WSEAS International Conference on BIOMEDICAL ELECTRONICS and BIOMEDICAL INFORMATICS

CH3 O Mg.1-propen-1-yl-carboxylate-. porphin. (CO-)3 C C O (13) [13] H C + . H OC C CH3 O C C O N H C N .. CO Mg OC C N N

N N CO Mg

N N Mg.1-propen-1-yl-carboxylate-.porphin.CHO.(CO- + )2 (14) [14]

Mg.1-propen-1-yl-carboxylate-. porphin. (CO-)3 Δ H = -0.40490 h (13) 3.8The formation of the neutral Mg.porphin. The enthalpy change is favourable. CH3.CH=CH.CO.CHO.(CO-)2

Δ H = -0.12229 h Mild hydrogenation allows the freeing of the alkenyl ester from the magnesium ion. The slightly simpler compound, Mg.3-methyl-1-oxo-but-1-en-2-yl.porphin.CO was Mg.1-propen-1-yl-carboxylate-.porphin.CHO.(CO- used to determine the activation energy to form the + - )2 + H → ester bond, by stretching the single bond, -C-O-, of the ester grouping, -(C=O)-C-O-. The activation energy to form the bond was found to be minimal, CH 0.007 h, whilst the energy to sever the bond was 3 O C 0.021 h. H C C H O . H OC C 3.7 The formation of the Mg.1-propen-1-yl- + carboxylate-. porphin. CHO.(CO-)2 N N CO Mg

The glycerol ester complex is considerably N N stabilised by protonation as shown,

Mg.1-propen-1-yl-carboxylate-. porphin. (CO-)3 + H+ → Mg.porphin.CH3.CH=CH.CO.CHO.(CO-)2 (15) [15]

Δ H = -0.42101 h

The enthalpy change is favourable.

3.9 The formation of Gycerol 1-butenate

ISSN: 1790-5125 57 ISBN: 978-960-474-110-6 Proceedings of the 2nd WSEAS International Conference on BIOMEDICAL ELECTRONICS and BIOMEDICAL INFORMATICS

Further mild reduction completely frees the glycerol [5] N.Aylward, and N.R.Bofinger, “Possible origin 1-butenate from the catalyst. for porphin derivatives in prebiotic chemistry - a computational study,” Orig.Life Evol. Mg.porphin.CH3.CH=CH.CO.CHO.(CO-)2 +3H2 → Biosph.vol.35(4), pp345-368,2005. [6]. T.S.Stevens,”The pyrrole pigments”, in Rodd,E.H.(ed), Chemistry of Carbon Compounds, Mg.porphin + Elsevier, Amsterdam,1V B, pp.1012-1047. HOCH2.CH(OH).CH2.O.CO.CH=CH.CH3 pp.1104-1162,1959. glycerol 1-butenate [7]. S.L.Miller and L.E.Orgel, The Origins of Life on Earth, Prentice-Hall Inc.,Englewood Cliffs, N.J. The enthalpy change is favourable, ,1975. Δ H = -0.16978 h [8] H. J. Cleaves II, The prebiotic geochemistry of formaldehyde ,Precambrian Research,Volume 164, 4. Conclusion Issues 3-4, pp.111-118,2008. [9] N.N.Aylward, and N.R.Bofinger, “Carbon Carbon monoxide is one of the most abundant monoxide clusters in the formation of D-sugars and molecules in the Universe [18], and in condensed L-amino-acids in prebiotic molecular evolution on phase readily forms both C-C and C-O bonds [19]. Earth,” in G.Palyi, C.Zucchi, L.Cagliotti, (eds.), The presence of reactants, carbon monoxide, Progress in Biological Chirality, Elsevier,Oxford alkynes and hydrogen in the early Earth’s (GB), ch2,pp429,2004.. atmosphere together with the catalyst porphin, [10] N.N. Aylward, “The synthesis of terpenes in suggests that thermodynamically and kinetically prebiotic molecular evolution on Earth,” in WSEAS viable reactions such as those presented here, could New Aspects of Biomedical Electronics and have formed a prebiotic photochemical directed Biomedical Informatics. Eds. C.A.Long, P.Anninos, template for glyceride synthesis. T.Pham, G.Anastassopoulos, N.E.Mastorakis Further work at a higher accuracy may alter the pp.202-207,2008. values given here. [11] Gaussian98, Users Reference,Gaussian Inc.,Carnegie Office Park, Bldg.6., Pittsburgh, PA 15106, USA,1998. 5 Acknowledgements [12] W.J.Hehre, L.Random, P.V.R. Schleyer, and The advice and support given by Professor Curt J.A.Pople, Ab Initio Molecular Orbital Theory, Wentrup of Queensland University is gratefully Wiley, New York.,1986. acknowledged. [13].J.A.Pople, H.B.Schlegel, R.Krishnan, D.J. Appreciation is also expressed to Queensland DeFrees, J.S. Binkley, M.J. Frisch, R.A.Whiteside, University of Technology; to Mr. A. Lewis, and Dr. R.J.Hout and W.J.Hehre, “Molecular orbital studies J. Young, M. Barry, and B. Savage, of the of vibrational frequencies,” Int.J.Quantum Chem. Supercomputing Department, and for the APAC Symp. vol.S15, pp269-278.1981 facilities at the ANU and QMAS facilities at UQ, [14]. J.P.Collman, L.S.Hegedus, J.R.Norton, R.G. and the assistance of Mr.M. Nicholls. Finke, "Principles and Applications of Organotransition Metal Chemistry", University Science Books, Mill Valey, California,,1987. References [15] D. Mansuy, J.P. Battioni, D. Dupre, E. Sartori, G. Chottard,”Reversible iron-nitrogen migration of [1]. A.L.Lehninger, Biochemistry,Worth, New York alkyl, aryl, or vinyl groups in iron porphyrins: a ,1975. possible passage between .sigma. [2]. M.Gurr, J.Harwood and K.Frayn, Lipid FeIII(porphyrin)(R) and FeII(N- Biochemistry: An Introduction, Blackwell Science, R)(porphyrin)complexes, J. Am. Chem. Soc., 104 London, 2002. (22), pp 6159–6161, 1982, [3]. C.E.Dalgliesh, A.G.Long, and G.J.Tyler, [16]. S.F.Birch, in J.W.Cook,(ed), Progress in “Trihydric alcohols and their oxidation products”: Organic Chemistry, Butterworths, London,1952 in Rodd,E.H.(ed), Chemistry of Carbon Compounds, [17] N.N.Aylward, “A prebiotic stereospecific Elsevier, Amsterdam,1 B, pp.1012-1047,1952. synthesis of biotin analogues,” in WSEAS Advanced [4].E.E.Conn, and P.K.Stumpf, ”Outlines of Topics in Mathematical Biology. Eds. P.Anninos, Biochemistry”,John Wiley.N.Y.,1972. T.Pham, A.Grebennikov. pp92-97,2008. ..

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[18] D.L.Cooper and K.J.Kirby, “Theoretical study of low-lying 1Σ+ and 1Π states of CO.1.Potential energy curves and dipole moments,” J.Chem.Phys. vol. 87(1),pp424-432,1987. [19]. K.K.Hartley, A.R.Wolff, and L.D.Travis, “Croconic acid: an absorber in the Venus Clouds”, Icarus, 77(2),pp.382-390,1989.

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