A Computational Study of a Prebiotic Synthesis of Menaquinone,

Phylloquinone, and Vitamin K Analoges

NIGEL AYLWARD

BMS Education Services Company,

Sea Meadow House,

Road Town, Tortola,

BRITISH VIRGIN ISLANDS

Abstract: - Ab initio applied computing is used to determine the viability of a plausible mechanism for the

formation of vitamin K from planetary and interstellar gases that contain the necessary essential elements in

prebiotic chemistry before the advent of life on Earth. The immutable laws of chemical thermodynamics and

kinetics enable the intermediates in the synthesis to be characterized and the activation energies to be

established. The planetary molecules propyne, ethyne, carbon monoxide, hydrogen, and water are invoked in a

synthesis of menaquinone, a naphthoquinone precursor of the vitamin K series of molecules. The enthalpy

change was -0.43 h. This is followed by the formation of oligomers of the gases propyne and ethyne which

serve as side-chains for the analogs of vitamin K where the enthalpy change was -0.21 h for the 2-methyl

butane side-chain. For vitamin K (n=1), the total enthalpy change was -0.63 h. The additional presence of

hydrogen cyanide gas and magnesium ions enables the surface-catalyzed, photochemically activated synthesis

of the catalyst, magnesium metalloporphyrin. The activation energies for the formation of intermediates on the

surface of the catalyst are less than the first excitation energy, 0.21 h. Finally, the menaquinone derivative and

the 2-methyl butane or 2-methyl butene oligomer derivatives are combined to give specific analogs of vitamin

K. The reactions are feasible from the overall enthalpy changes in the ZKE approximation at the HF and MP2

/6-31G* level and with acceptable activation energies.

Key-Words: - Prebiotic photochemical synthesis, menaquinone, phylloquinone, Vitamin K1, Vitamin K2,

Mg.porphin.

Received: Septermber 16, 2023. Revised: July 14, 2024. Accepted: August 17, 2024. Published: September 11, 2024.

1 Introduction

Vitamin K is a group of structurally similar, 2-

methyl-1,4-naphthoquinone derivatives, which

belong to the group of natural quinones comprising

the classes anthraquinones, naphthoquinones and

benzoquinones [1], with at least five accompanying

biosynthetic pathways, [2]. The substituent of the

napthoquinone defines the exact vitamin K, [3].

There are two natural forms of vitamin K

homologues, plant-derived vitamin K1 such as

phylloquinone and the bacterium-derived vitamin

K2, Figure 1. For example, vitamin K1

(phylloquinone) has a 3-phytyl substituent while

vitamin K2 contains repeating unsaturated isoprene

units at the 3 position. The menaquinones may be

denoted as MK-n, (menaquinone-n, MK-n), [4],

where n is the number of repeating isoprene units.

The other form of vitamin K encountered is 2-

methyl-1,4-naphthoquinone (vitamin K3 or

menadione) which lacks substitution at the 3

position. Although biologically active in vivo this

compound is not found in nature, [5], [6].

The vitamin K1 series of molecules, Figure 1,

such as phylloquinone occur primarily from plants,

especially leafy green vegetables such as spinach,

brussels sprouts and broccoli, and animal products

such as chicken, mollusks and cheese. The Vitamin

K2 series, Figure 1, is present in bacteria, [5], which

can also convert vitamin K1 into vitamin K2, [7]. .

Vitamin K2 is primarily from animal-sourced foods,

with poultry and eggs much better sources than

beef, pork or fish, [8]. Vitamin K is found in the

tissues of all animals, [5].

It is essential for the biosynthesis of the enzyme

proconvertin in the liver which catalyzes a step in

the sequence of reactions involved in the formation

of prothrombin, [9], the precursor of thrombin, [10],

a proteolytic enzyme that accelerates the conversion

of fibrinogen into fibrin, the insoluble protein

constituting the fibrous portion of blood clots.

Analogs of Vitamin K are used to assist blood

clotting whilst antagonists are used to prevent blood

clotting, [10]. The molecules are napthoquinone

derivatives that may function as coenzymes in the

WSEAS TRANSACTIONS on BIOLOGY and BIOMEDICINE

DOI: 10.37394/23208.2024.21.26

Nigel Aylward

E-ISSN: 2224-2902

249

Volume 21, 2024

electron transport system in animals where they can

be reversibly reduced to quinols, [11]. Deficiency of

vitamin K may also weaken bones, and may

promote calcification of arteries, [12], [13], [14].

Both K1 and K2 are cofactors for the enzyme γ-

glutamyl carboxylase, which converts glutamic acid

(Glu) to a new amino acid γ-carboxyglutamic acid

(Gla), in vitamin K-dependent proteins during their

biosynthesis, [15], [16]. These γ-carboxyglutamic

acid residues have a high affinity for positively

charged calcium ions, [17]. MK-4 has the selective

ability to cause differentiation of neural progenitor

cells NPCs, derived from mouse cerebrum into

neuronal cells. Vitamin K homologues also have

been reported to play a role in preventing oxidative

injury to developing oligodendrocytes and neurons,

[18], [19]. Vitamin K (VK) has an important part in

ageing, [20], [21], [22]. The organic synthesis is

accomplished, [23] and the biosynthesis, [24].

From a prebiotic perspective, [25], it is desirable

if the reactant molecules formed spontaneously from

a supposed prebiotic atmosphere to be inevitably

present. It has often been held that the atmosphere

of the Earth was originally mildly reducing, [5],

[26], implying the presence of concentrations of

carbon monoxide, ammonia, water, and hydrogen.

It is also supposed that the napthoquinone residue

was formed from the gases ethyne, propyne, carbon

monoxide and water, whilst the variable long-chain

side-chains in the different series were also formed

from the oligomerization of the gases ethyne and

propyne. The structure of these molecules strongly

suggests a copolymerization. This paper describes

the initial formation of the napthoquinone

derivative, and the subsequent addition of the side-

chain oligomers of ethyne and propyne. The

copolymerization is described as requiring the

Mg.porphin catalyst with photochemical activation.

These reactions are assumed to occur mainly in the

liquid phase, [27].

The reactions described have been deduced as

kinetically and thermodynamically viable, but

photochemical excitation is required.

2 Problem Formulation

This proposed computational study of a plausible

synthesis of the vitamin K analogs involves the

calculation of the enthalpy changes for reaction

intermediates in the ZKE approximation and the

calculation of activation energies at the HF level.

These activation energies may all be accessible as

the catalyst may absorb appreciable photochemical

activation (0.21 h). The computations tabulated in

this paper used the GAUSSIAN09, [28].

The standard calculations at the HF and MP2

levels including zero-point energy corrections at the

Hartree Fock level, [29], together with scaling, [30],

using the same basis set, 6-31G*, are as previously

published, [25]. Enthalpy changes at the MP2 level

not including scaled zero point energies are

designated as ΔH(MP2). The charge transfer

complexes are less stable when calculated at the

Hartree Fock level, [29], and activation energies

calculated at the HF level without scaling are less

accurate.

If the combined energy of the products is less

than the combined energy of the reactants it may

show that the reaction is also likely to be

spontaneous at higher temperatures. This paper uses

the atomic unit of energy, the hartree, [28].

1h = 627.5095 kcal.mol-1. 1h = 4.3597482 x 10-

18 J

Mullikan charges are in units of the electronic

charge.

3 Problem Solution

3.1 Total Energies (hartrees)

The initial reactants in this proposed prebiotic

synthesis of vitamin K compounds are the simple

gases, propyne, ethyne, carbon monoxide, water,

and hydrogen.

For these molecules to copolymerize it is here

postulated that a catalyst is desirable, taken to be

Mg.porphin, [31], [32]. The immutable laws of

chemical thermodynamics and kinetics then dictate

unequivocally that feasible reactions will occur

provided the physical conditions are conducive to

chemical reactions.

Some of the reactions that may be expected in

the gaseous and liquid phases are given here as

forming the initial reactant molecules to synthesize

compounds collectively called vitamin K analogs.

Here the compounds will be limited to

phylloquinone and its simple derivatives where the

side-chain extension is just n=1 to 3, as shown in

Figure 1.Vitamin K2 represents a group of

molecules with a varying number of isoprene units

as side-chains. Each molecule can be named MK-n,

which represents the number of isoprene units it

contains, [12].

The reactants are expected to have been present

at some concentration over eons predicated on the

Earth’s atmosphere being mildly reducing at some

time past.

The intermediates by which these could form

vitamin K are listed in Table 1. The catalyst for the

formation of the alkyne copolymers is Mg.porphin.

WSEAS TRANSACTIONS on BIOLOGY and BIOMEDICINE

DOI: 10.37394/23208.2024.21.26

Nigel Aylward

E-ISSN: 2224-2902

250

Volume 21, 2024

Table 1. MP2 /6-31G* total energies and zero point

energies (hartrees) for the respective equilibrium

geometries

Molecule HF MP2 ZPE (HF)

hartree hartree hartree

propyne (1) -116.24181 0.06010

Mg.porphin (2) -1185.12250 0.29262

Mg.1,2-dehydro 4-methyl-pent-1.3-diene.porphin (3)

-1417.6182 0.41981

Mg.1,porphin.2-dehydro 4-methyl-pent-1.3-diene (4)

-1417.59302 0.43597

Mg.1,CO.porphin.2-dehydro 4-methyl-pent-1.3-diene (5)

-1530.61235 0.41980

Mg.1,1-carbonyl 3-dehydro 5-methyl-hex-2.4-diene.porphin (6)

-1530.64911 0.41854

Mg.1,porphin.1-carbonyl 3-dehydro 5-methyl hex-2.4-diene (7)

-1530.64162 0.42353

Mg.1,7-carbonyl 9-dehydro 11-methyl 1,3,5,8,10-

penta diene dodecane.porphin (8)

-1761.81844 0.53021

Mg.1,porphin.7-carbonyl 9-dehydro 11-methyl

1,3,5,8,10-penta diene dodecane (9)

-1761.82962 0.53981

cis isomer of Mg.1,porphin.7-carbonyl 9-dehydro

11-methyl 1,3,5,8,10-penta diene dodecane (10)

-1761.42438 0.53272

Mg.1,porphin.2-(1-carbonyl 3-dehydro 5-methyl

hex-2,4-dien-1yl).cyclohex-3,5-diene-1yl (11)

-1761.82588 0.53201

Mg.1,propyn-1yl.porphin.2-(1-carbonyl 3-dehydro

5-methyl hex-2,4-dien-1yl).cyclohex-3,5-dien-1yl.(12)

-1877.95859 0.60048

Mg.1,3-(1-carbonyl-2-(cyclohex 3,5-dien-N-2yl))

-4-didehydro-6-methyl 1,5-hept-diene-1yl.porphin (13)

-1878.04640 0.60931

Mg.1,2-methyl 3-(1-didehydro 3-methyl but 2-en

-1yl) 4-keto 9.10 dihydro. napthalene.porphin.

(14) -1878.18966 0.60353

Mg.1,2-dehydro 2-methyl 3-(3-methyl but 2-en -1yl) 4-keto

napthalene.porphin

(15) -1878.41087 0.61127

4-hydro 4-hydroxy 3,methyl 2-(3-methyl but-2-ene) 1-

napthaquinone

(16) -768.47556 0.32220

2-methyl 3-(3-methyl but-2-ene) 1,4 napthaquinone (17)

menaquinone

-767.31923 0.29854

phylloquinone (18) -963.13714 0.44772

2-methylbutane -196.99336 0.17139

2-methylbutene -195.79496 0.14578

1,4 napthoquinone -533.50568 0.13218

1,4 dihydroxy napthoquinine

-534.58088 0.15354

4-hydro 4-hydroxy 1,4 napthaquinone

-534.66201 0.15584

ethyne -77.06680 0.02945

H.. -0.49823

CO -113.02122 0.00566

OH. -75.52257 0.00911

OH- -75.51314 0.00816

H2O -76.19685 0.02045

H2 -1.14414 0.01056

The standard numbering nomenclature for

naphthalene derivatives is given in Figure 1.

K1 Series (phylloquinone)

K2 series, MK-n (menaquinone, n=1)

2-methyl-1,4-naphthoquinone (vitamin K3 or

menadione)

Fig. 1: The standard numbering for naphthalene.

Vitamin K series. 2-methyl-1,4-

naphthoquinone with polyisoprenyl side chain at

position 3 for the K2 series and saturated side-chain

for the K1 series.

These complexes are integral reactants in the

proposed synthesis. The energies of the stable

complexes to form the menaquinone and 2-methyl

butane oligomers are shown in Table 1.

3.2 The Overall Stoichiometry for the

Formation of the Vitamin K1, Series

(n=1)

Initially vatamin K1 analogue (n=1), Figure 2, is

synthesized, where the stoichiometry is given as,

CO + 4CH3-C ≡ C-H + 4H-C ≡ C-H + H2O →

C21H26O2

K1

ΔH = -0.63040 h

Fig. 2: vitamin K1 series (n=1)

To save computer time the molecule is split into

the napthalene derivative, menaquinone, Figure 3,

WSEAS TRANSACTIONS on BIOLOGY and BIOMEDICINE

DOI: 10.37394/23208.2024.21.26

Nigel Aylward

E-ISSN: 2224-2902

251

Volume 21, 2024

and the side-chain substituent alkane, 2-methyl

butane, Figure 4.

Fig. 3: Menaqinone (n=1)

The overall stoichiometry to form the menaquinone,

MK (n=1), Figure 3, is as follows,

CO + 3CH3-C ≡ C-H + 3H-C ≡ C-H + H2O →

C16H16O2 + 2H2,

ΔH = -0.44360 h

The overall stoichiometry to form the 2-methyl

butane, Figure 4, is as follows,

H-C ≡ C-H + CH3-C ≡ C-H + 3H2 → C5H12

ΔH = -0.20776 h

CH3-CH2- CH(CH3)-CH3

Fig. 4: 2-methyl butane

Finally the two are combined according to the

equation,

menaquinone + 2-methylbutane → vitamin K1

(n=1) + H2

ΔH = -0.63040 h

It is assumed that the enthalpy changes involved

in the synthesis of these two simpler molecules are

the same as those involved in the formation of the

vitamin K1 (n=1) molecule.

The enthalpy change is negative indicating that

this may be the energetically favourable route to the

initial formation of the vitamin K1 series. The

intermediates by which these stoichiometric

reactions may have occurred are as follows:

Molecules are numbered consecutively.

Subsections depict alternatives in the sequence

of the reaction mechanism.

A standard numbering of the atoms in the

napthalene molecule is shown in Figure 1.

3.3 The Formation of Mg.1,2-dehydro 4-

methyl-pent-1.3-diene.porphin

The prebiotic photochemically activated , surface

catalysed synthesis of Mg.1,2-dehydro 4-methyl-

pent-1.3-diene.porphin has been described, [33],

where the catalyst was taken as Mg.porphin, [25],

the same catalyst is used in this synthesis of vitamin

K where the initial reactant is the gas propyne. Here,

those first reactions are summarized and represented

here as,

2 CH3-C ≡ C-H + Mg.porphin →

(1) (2)

Mg.1,2-dehydro 4-methyl-pent-1.3-diene.porphin

(3)

ΔH = -0.07948 h

The reaction appears marginally feasible having

been excited photochemically on the surface

catalyst..

The activation energy in these charge transfer

reactions or the formation of van der Waals

complexes is always achievable as the catalyst can

absorb considerable photochemical activation, 0.21

h, [33]

At this stage in the synthesis of vitamin K

analogues very long side-chains from 1 to 50

isoprenyl groups may be added, [34], and

hydrogenated with various sterically specific side-

chains. These are postponed until later.

3.4 The Formation of Mg.1,porphin.2-

dehydro 4-methyl-pent-1.3-diene

The Mg.1,2-dehydro 4-methyl-pent-1.3-diene.

porphin may be excited to an alternative energy

state, as,

-

N

Mg

N

C

H

C

+

H3CH3C

H

WSEAS TRANSACTIONS on BIOLOGY and BIOMEDICINE

DOI: 10.37394/23208.2024.21.26

Nigel Aylward

E-ISSN: 2224-2902

252

Volume 21, 2024

Mg.1, .porphin .2-dehydro 4-methyl pent-1.3-diene

(3) →

Mg.1, .porphin. 2-dehydro 4-methyl-pent-1.3-diene.

(4)

ΔH = 0.11318 h

At HF level the activation energy for the addition

was the same as the enthalpy change.

3.5 The Formation of Mg.1,CO.porphin.2-

dehydro 4-methyl-pent-1.3-diene

Further condensation may result in a carbon

monoxide molecule being added to the magnesium

binding site, as,

CO + Mg.1,porphin.2-dehydro 4-methyl-pent-

1.3-diene →

Mg.1,CO.porphin.2-dehydro 4-methyl-pent-1.3-

diene (5)

ΔH = -0.01744 h

The addition reaction is favourable without

activation energy, [35].

3.6 The formation of Mg.1,1-carbonyl 3-

dehydro 5-methyl-hex-2.4-

diene.porphin.

The two adducts may coallesce, as,

Mg.1,CO.porphin. 2-dehydro 4-methyl-pent-1.3-

diene →

Mg.1,1-carbonyl 3-dehydro 5-methyl-hex-2.4-

diene.porphin (6)

ΔH = - 0.03788 h

No activation energy was recorded for this

favourable reaction.

3.7 The formation of Mg.1,porphin.1-

carbonyl 5-methyl-pent-2.4-diene

The Mg.1,1-carbonyl 2-dehydro 5-methyl-hex-2.4-

diene.porphin may be excited to a higher energy

state as,

Mg.1,1-carbonyl 3-dehydro 5-methyl-hex-2.4-

diene.porphin →

Mg.1,porphin.1-carbonyl 3-dehydro 5-methyl-hex-

2,4-diene (7)

ΔH = 0.01193 h

The activation energy was the same as the enthalpy

change.

3.8 The Formation of Mg.1,7-carbonyl 9-

dehydro 11-methyl 1,3,5,8,10-penta

diene dodecane. porphin

At this stage in the synthesis it is desirable to add an

oligomer of three ethyne units, [36], to save on

computer time as,

Mg.1,porphin.1-carbonyl 3-dehydro 5-methyl-hex-

2.4-diene + 3 H-C ≡ C-H →

-

N

Mg

N

C

H

C

+

H3CH3C

H

-

N

Mg

N

C

H

C

+

H3CH3C

H

C

O

-

N

Mg

N

C

H

C

+

H3CH3

C

H

C

O

-

N

Mg

N

C

H

C

+

H3CH3

C

H

C

O

WSEAS TRANSACTIONS on BIOLOGY and BIOMEDICINE

DOI: 10.37394/23208.2024.21.26

Nigel Aylward

E-ISSN: 2224-2902

253

Volume 21, 2024

Mg.1,7-carbonyl 9-dehydro 11-methyl 1,3,5,8,10-

penta diene dodecane.porphin (8)

ΔH = 0.03986 h

The activation energy was the same as the enthalpy

change.

3.9 The Formation of Mg.1,porphin. 7-

carbonyl 9-dehydro 11-methyl 1,3,5,7,9-

penta diene dodecane.

The Mg.1,7-carbonyl 9-dehydro 11-methyl

1,3,5,8,10-penta diene dodecane.porphin

may be excited to a higher energy state as,

Mg.1,7-carbonyl 9-dehydro 11-methyl 1,3,5,8,10-

penta diene dodecane.porphin

→

Mg.1,porphin.7-carbonyl 9-dehydro 11-methyl

1,3,5,8,10-penta diene dodecane (9)

ΔH(HF) = -0.00163 h

No activation energy was recorded for the formation

of this isomeric state.

3.10 The Formation of a cis isomer of

Mg.1,porphin.7-carbonyl 9-dehydro

11-methyl 1,3,5,8,10-penta diene

dodecane

The Mg.1,porphin.7-carbonyl 9-dehydro 11-methyl

1,3,5,8,10-penta diene dodecane

may be excited by radiation to undergo three

consecutive cis rotational energy changes which

requires activation energy, [36], as,

Mg.1,porphin.7-carbonyl 9-dehydro 11-methyl

1,3,5,8,10-penta diene dodecane →

A cis isomer of Mg.1,porphin.7-carbonyl 9-dehydro

11-methyl 1,3,5,8,10-penta diene dodecane (10)

ΔH(HF) = 0.397922 h

This requires three separate rotational activation

energies provided by the catalyst.

3.11 The Formation of Mg.1,porphin.2-(1-

carbonyl 3-dehydro 5-methyl hex-2,4-

diene-1yl).cyclohex-3,5-dien-1yl

The cis isomer of Mg.1,porphin.7-carbonyl 9-

dehydro 11-methyl 1,3,5,8,10-penta diene dodecane

may be excited for ring closure to occur and be

bonded at the excited higher energy adduct site as,

cis isomer of Mg.1,porphin.7-carbonyl 9-dehydro

11-methyl 1,3,5,8,10-penta diene dodecane →

Mg.1,porphin.2-(1-carbonyl 3-dehydro 5-methyl

hex-2,4-diene-1yl).cyclohex-3,5-dien-1yl (11)

ΔH = -0.40212 h

.

-

N

Mg

N

C

H

C

+

H3CH3

C

H

C

O

CC

C C

HH

H

-

N

Mg

N

C

H

C

+

H3CH3

C

H

C

O

CC

C C

HH

H

-

N

Mg

N

C

H

C

+

H3CH3

C

H

C

O

C

CC

C

H

-

N

Mg

N

C

HC

C

+

H3CH3

C

H

C

O

C

CC

C

H

WSEAS TRANSACTIONS on BIOLOGY and BIOMEDICINE

DOI: 10.37394/23208.2024.21.26

Nigel Aylward

E-ISSN: 2224-2902

254

Volume 21, 2024

3.12 The Formation of Mg.1,propyn-

1yl.porphin.2-(1-carbonyl 3-dehydro

5-methyl hex-2,4-diene-1yl).cyclohex-

3,5-dien-1yl

The Mg.1,porphin.2-(1-carbonyl 3-dehydro 5-

methyl hex-2,4-diene-1yl).cyclohex-3,5-dien-1yl

may add a propyne adduct on the vacant

Mg.porphin site as,

Mg.1,porphin.2-(1-carbonyl 3-dehydro 5-methyl

hex-2,4-diene-1yl).cyclohex-3,5-dien-1yl

+ propyne →

Mg.1,propyn-1yl.porphin.2-(1-carbonyl 3-dehydro

5-methyl hex-2,4-diene-1yl).cyclohex-3,5-dien-1yl.

(12)

ΔH = 0.11655 h

These charge transfer complexes form

spontaneously, [35].

3.13 The Formation of Mg.1,3-(1-carbonyl-2-

(cyclohex-3,5-dien-N-2yl))-4-didehydro-

6-methyl 1,5-hept-dien-1yl

Further bonding may occur between the di-ene

groups to produce a diradical as,

Mg.1,propyn-1yl.porphin.2-(1-carbonyl 3-dehydro

5-methyl hex-2,4-diene-1yl).cyclohex-3,5-dien-1yl

→

Mg.1,3-(1-carbonyl-2-(cyclohex 3,5-diene-N-2yl))-

4-didehydro-6-methyl 1,5-hept-dien-1yl.porphin

(13)

ΔH = -0.07989 h

The activation energy was calculated as 0.0 h, as

they spontaneiously coalesce.

3.14 The Formation of Mg.1,2-dehydro 2-

methyl 3-(1-didehydro 3-methyl but 2-

ene-1yl) 4-keto 9.10 dihydro

napthalene.porphin

Further condensation may occur to form a

napthalene derivative as,

Mg.1,3-(1-carbonyl-2-(cyclohex-3,5-diene-N-2yl)-

4-didehydro-6-methyl 1,5-hept-diene-1yl →

Mg.1,2-methyl 3-(1-didehydro 3-methyl but 2-en-

1yl) -4-keto 9.10 dihydro napthalene.porphin. (14)

ΔH = - 0.14847 h

The activation energy for the condensation was

negligible.

3.15 The Formation of Mg.1,2-methyl 3-(3-

methyl but 2-ene-1yl) 4-keto napthalene

.porphin

Further isomerization may occur as,

Mg.1,2-methyl 3-(1-didehydro 3-methyl but 2-en-

1yl) napthalen 4-keto 9.10 dihydro.porphin ->

Mg.1,2-dehydro 2-methyl 3-(3-methyl but 2-ene-

1yl) 4-keto napthalene.porphin (15)

ΔH = - 0.24636 h

-

N

Mg

N

C

HC

C

+

H3CH3

C

H

C

O

C

CC

C

H

HC

HCH3

C

-

N

Mg

N

C

HC

C

H3CH3

C

H

C

O

C

CC

C

H

HCH

CH3

C

..

-

N

Mg

N

C

HC

C

H3CH3

C

H

C

O

C

CC

C

H

HH

HC

H

CH3

C

..

+

-

N

Mg

N

C

HC

C

H3CH3

C

H

C

O

C

CC

C

H

C

H

CH3

C

+

H2

WSEAS TRANSACTIONS on BIOLOGY and BIOMEDICINE

DOI: 10.37394/23208.2024.21.26

Nigel Aylward

E-ISSN: 2224-2902

255

Volume 21, 2024

The activation energy to add molecular hydrogen to

the di-radical is zero.

3.16 The Formation of 3-methyl 2-(3-methyl

but-2-ene) 4-hydro 4-hydroxy 1-

napthaquinone

The nascent vitamin K may be released from the

catalyst by the presence of hydrogen and hydroxyl

radicals, [37],

H2O → H.. + OH ..

ΔH = 0.16472 h

Mg.1,2-dehydro 2-methyl 3-(3-methyl but 2-ene-

1yl) 4-keto napthalene.porphin + H. + OH- → H2

+ Mg.porphin +

4-hydro 4-hydroxy 3-methyl 2-(3-methyl but-2-

ene) 1-napthaquinone (16)

ΔH = - 0.25840 h

The activation energy and enthalpy change for this

reaction are assumed to arise from the first

excitation of the Mg.porphin catalyst, 0.21 h.

3.17 The Formation of 2-methyl 3-(3-methyl

but-2-ene) 1,4 napthaquinone

The napthalene derivative may be oxidised by the

presence of hydrogen and hydroxyl radicals to lose a

hydrogen molecule as,

3-methyl 2-(3-methyl but-2-ene) 4-hydro 4-

hydroxy 1-napthaquinone → H2

+

2-methyl 3-(3-methyl but-2-ene) 1,4 napthaquinone

(17)

ΔH = 0.00055 h

The activation energy was the same as the enthalpy

change.

3.18 The Formation of Vitamin K1 (n=1)

For the explicit formation of this vitamin K1 (n=1)

analoque it is assumed that the enthalpy changes

recorded for the above, menaquinone and 2-

methylbutane are the same as those for the

formation of vitamin K1 (n=1). Here the two

molecules are bonded with the exclusion of a

hydrogen molecule, according to the equation,

menaquinone + 2-methylbutane → vitamin K1

(n=1) + H2

ΔH = -0.63060 h

3.19 The Formation of Phylloquinone

The K1 (n=3) vitamin K1, Figure 1, which occurs

naturally may be formed by the same sequence of

reactions according to the equation,

menaquinone + 3 2-methylbutane → 3 H2 +

vitamin K1 (n=3)

phylloquinone (18)

ΔH = -0.90906 h

3.20 The formation of vitamin K analoques

This polymerization method may also be used to

calculate the energies of the K2 series using 2-

methylbutene, as,

n 2-methylbutene → (2-methylbutene)n + n H2

3.20.1 The Formation of Reduced Vitamin K-1

Analoges

The order of the enthalpy change in the reduction of

2-methyl 3-(3-methyl but-2-ene) 1,4 napthoquinone

may be studied using the simpler compound, 1,4-

napthoquinone, as,

1,4-napthoquinone + H2 → 1,4-napthoquinol

ΔH = -0.00055 h

3.20.2 The Formation of Reduced Vitamin K-1

Analoges

The enthalpy change in the reduction of 2-methyl

3-(3-methyl but-2-ene) 1,4 napthoquinone .may

also proceed to produce a semi reduced 1,4-

napthoquinone as,

C

H3CH3

C

H

C

O

C

CC

C

H

C

H

CH3

C

H2

OH

H

C

H3CH3

C

H

C

O

C

CC

C

H

C

H

CH3

C

H2

O

WSEAS TRANSACTIONS on BIOLOGY and BIOMEDICINE

DOI: 10.37394/23208.2024.21.26

Nigel Aylward

E-ISSN: 2224-2902

256

Volume 21, 2024

1,4-napthoquinone + H2 → 4-hydro 4-hydroxy -

napthoquinone

ΔH = - 0.02146 h

4 Conclusion

The present biochemistry is via the shikimic acid

pathway, [38], which is sequentially demanding and

requires multistep enzyme activation. The

postulated prebiotic synthesis is much simpler, just a

simple copolymerization, and requires just the

ancient catalyst, metalloporphin, [39], itself

reasonably formed from diacetylene cyanide, [25]

together with the most prevalent gases in the

Universe, [40], and interstellar hydrocarbynes and

water, [41], [42].

The wide range for the length of the side chains

in the vitamin series K1 and K2 series does suggest

they arose from copolymerization of simple alkyne

gases of ancient atmospheres that were mildly

reducing. The enthalpy changes and activation

energies calculated do confirm this as much as

possible. An experiment would be useful to see if

vitamin K was indeed formed.

Further work may concentrate on why certain

vitamins have specific stereochemistry that is

preserved in present biochemistry and how the

length of the side chain affects the reduction of the

1,4 quinones. The existence of this molecule in

hydrogen transport reactions and its widespread

occurrence in biochemistry suggest it is of extreme

antiquity

Further work at a higher accuracy may alter the

values given here.

Acknowledgement:

Appreciation is expressed to Gaussian Inc. and Q-

Chem.

References:

[1] R. H. Thomson, Naturally Occurring

Quinones, 2nd edn., Academic Press: New

York, 1971.

[2] R. Bentley, in Biosynthesis (Specialist

Periodical Report-The Chemical Society), 3,

1975, pp.181. .

[3] A. M. Daines, R.J. Payne, M.E. Humphries,

and A.D. Abell, The synthesis of naturally

occurring vitamin K and vitamin K analogs,

Current Organic Chemistry, 7, 2003, pp.1-

151.

[4] J.Conly, K.Stein, L.Worobetz, S.Rutledge-

Harding, The contribution of vitamin K2

(menaquinones) produced by the intestinal

microflora to human nutritional requirements

for vitamin K. Am. J. Gastroenterol.89, 1994,

pp.915–923.

[5] A.L.Lehninger, Biochemistry, Worth, New

York, 1975, pp. 358.

[6] International Agengy for Research on Cancer

(IARC).,Vitamin K. Monographs on the

evaluation of carcinogenic risks to humans, -

Some antiviral and antineoplastic drugs, and

other pharmaceutical agents. Lyon, 76, 2000;

pp.417-473.

[7] E.E.Conn and P.K.Stumpf, Outlines of

Biochemistry, J.Wiley, 1972.

[8] D.C.Simes, C.S.B. Viegas, N.Araújo,

C.Marreiros, Vitamin K as a diet supplement

with impact in human health: Current

evidence in age-related diseases. Nutrients 12,

2020, pp.138-162,

https://doi.org/10.3390/nu12010138.

[9] E.D.Wills, Biochemical basis of medicine,

Pitman Press. UK, 1985, pp.325.

[10] R.H. Wasserman and A.N.Taylor, Metabolic

roles of fat-soluble vitamins, D, E and K. Ann.

Rev.Biochem. 41, 1972, pp.179.

[11] S.Margueritta, El.Asmar, J. J. Naoum and E.

J. Arbid, Vitamin K dependent proteins and

the role of vitamin K2 in the modulation of

vascular calcification: A review, Oman

Medical Journal, 29(3), 2014, pp. 172-177.

[12] B.P. Marriott, D.F. Birt, V.A. Stallings, A.A.

Yates, eds. Vitamin K, Present knowledge in

nutrition, Academic Press (Elsevier). 2020,

pp. 137–54.

[13] C.M.Giachelli,. Vascular calcification

mechanisms. J Am Soc Nephrol., 2004,

15(12), pp.2959-2964.

[14] L.L.Demer and Y. Tintut. Vascular

calcification: pathobiology of a multifaceted

disease. Circulation, 117(22), 2008, pp.2938-

2948.

[15] M.Halder, P. Petsophonsakul, A.C.Akbulut,

A. Pavlic, F.Bohan, E.Anderson, K.Maresz,

R.Kramann and L.Schurgersl., Vitamin K:

double bonds beyond coagulation insights into

differences between Vitamin K1 and K2 in

health and disease. Int. J. Mol. Sci., 20, 2019,

pp. 896..

[16] F.Wei, S.Trenson, P.Verhamme, C.Vermeer,

J.A.Staessen, Vitamin K-dependent matrix

Gla protein as multifaceted protector of

vascular and tissue integrity. Hypertension,

73, 2019, pp.1160-1169.

WSEAS TRANSACTIONS on BIOLOGY and BIOMEDICINE

DOI: 10.37394/23208.2024.21.26

Nigel Aylward

E-ISSN: 2224-2902

257

Volume 21, 2024

[17] A.F.Zebboudj, M.Imura,K. Boström,. Matrix

GLA protein, a regulatory protein for bone

morphogenetic protein-2. J Biol Chem.,

277(6): 2002, pp. 4388-4394.

[18] J.Li, J.C.Lin, H.Wang, J.W.Peterson,

B.C.Furie, B.Furie, S.L.Booth, J.J..Volpe and

P.A. Rosenberg, . A. Novel role of vitamin K

in preventing oxidative injury to developing

oligodendrocytes and neurons. J. Neurosci.

23, 2003, pp.5816−5826.

[19] Y. Suhara, Y Hirota, N.Hanada, S. Nishina,

S.Eguchi, R.Sakane, K, Nakagawa, A, Wada,

K. Takahashi, K. H.Tokiwa, and T. Okano,

Synthetic small molecules derived from

natural vitamin K homologues that induce

selective neuronal differentiation of neuronal

progenitorcells. J. Med. Chem. 58, 2015, pp.

7088−7092.

[20] D.Popa, G.Bigman, and M.E. Rusu, The role

of Vitamin K in humans: Implication in aging

and age-associated diseases, Antioxidants,

10,566, 2021, pp.1- 31.

[21] D.Misra, S.L.Booth, I.Tolstykh, D.T.Felson,

M.C. Nevitt, C.E. Lewis, J.Torner, T.Neogi,

Vitamin K deficiency is associated with

incident knee osteoarthritis. Am. J. Med. 126,

2013, pp.243–248.

[22] D.C.Simes, C.S.B.Viegas, N. Araujo,

C.Marreiros, Vitamin K as a Powerful

Micronutrient in aging and age-related

diseases: pros and cons from clinical studies.

IJMS 20, 2019, pp.4150.

[23] V.Tachibana, Direct synthesis of vitamin K1

and K2, Chemistry Letters, 6(8), 1977, pp.

901–902, https://doi.org/10.1246/cl.1977.90

[24] S. Sánchez, N. & S.Coronado, R. & H.Carlos,

B. & V. Claudia. (2019). Shikimic Acid

Pathway in Biosynthesis of Phenolic

Compounds. 2019,10.5772/intechopen.83815.

[25] N. Aylward, and N.R.Bofinger, Possible

origin for porphin derivatives in prebiotic

chemistry - a computational study, Orig.Life

Evol. Biosph. vol.35 (4), 2005, pp.345-368.

[26] S.L. Miller and L.E.Orgel, The Origins of Life

on Earth, Prentice-Hall Inc., Englewood

Cliffs, N.J., 1975.

[27] K.Seki, M.He, R.Liu and H.Okabe,

Photochemistry of cyanoacetylene at 193.3

nm. J.Phys.Chem., 100, 1996, pp.5349-5353.

[28] Gaussian03, Users Reference, Gaussian Inc.,

Carnegie Office Park, Bldg.6, Pittsburgh, PA

15106, USA, 2003.

[29] W.J.Hehre, L.Random, P.V.R. Schleyer, and

J.A.Pople, Ab Initio Molecular Orbital

Theory, Wiley, New York, 1986.

[30] J.A.Pople, H.B.Schlegel, R.Krishnan, D.J.

DeFrees, J.S. Binkley, M.J. Frisch, Molecular

orbital studies of vibrational frequencies,

Int.J.Quantum Chem. Symp. vol.S15, 1981,

pp.269-278.

[31] J.P.Collman, L.S.Hegedus, J.R.Norton, R.G.

Finke, Principles and Applications of

Organotransition Metal Chemistry,

University Science Books, Mill Valey,

California,,1987.

[32] D.Mansuy, J.P.Battioni, D.Dupre, E.Sartori

and G.Chottard, Reversible iron-nitrogen

migration of alkyl, aryl, or vinyl groups in

iron porphyrins: a possible passage between

.sigma.FeIII (porphyrin)(R) and FeII(N-

R(porphyrin)complexes, J..Am.Chem.Soc.

104, 1982, pp.6159-6161

[33] N. Aylward, The synthesis of terpenes in

prebiotic molecular evolution on Earth. p.202-

207, WSEAS Int. Conf. on Biomedical

Electronics and Biomedical Informatics.

Rhodes Island, Greece, August 20-22, 2008.

[34] R.K Hammond and D.C. White, Separation of

vitamin K, isoprenalogues by reversed-phase

thin-layer chromatography, J.Chromatog., 45, 1969,

pp.446-452.

[35] N.N.Aylward, and N.R.Bofinger, Carbon

monoxide clusters in the formation of D-

sugars and L-amino-acids in prebiotic

molecular evolution on Earth, in G.Palyi,

C.Zucchi, L.Cagliotti, (eds.), Progress in

Biological Chirality, Elsevier, Oxford (GB),

2004, ch2, pp.429

[36] N. Aylward, A Computational Study of a

Prebiotic Synthesis of the Steroid

Progesterone (A and B Rings) WSEAS

transactions on biology and biomedicine 17,

2020, pp.9-17.

[37] K.Fong, Light Reaction Path of

Photosynthesis, Springer Verlag, 1982,

pp.344.

[38] N. F. Santos-Sánchez, R. Salas-Coronado, B.

Hernández-Carlos, and C. Villanueva-

Cañongo, Shikimic acid pathway in the

biosynthesis of phenolic compounds, Plant

Physiological Aspects of Phenolic

Compounds. IntechOpen, Sep. 04, 2019. doi:

10.5772/ intechopen.83815.

[39] R. Hooper, Revealing the dawn of

photosynthesis, New Scientist. 2006

[40] D.L.Cooper and K.Kirby, Theoretical study of

low-lying hydrogen 1Σ+ and 1Π states of CO.

1. Potential curves and dipole moments. J.

Chem. Phys., 97(1), 1987,pp.424-431.

WSEAS TRANSACTIONS on BIOLOGY and BIOMEDICINE

DOI: 10.37394/23208.2024.21.26

Nigel Aylward

E-ISSN: 2224-2902

258

Volume 21, 2024

[41] O.E. Pentsak, M.S. Murga and V. P.

Ananikov, Role of acetylene in the chemical

evolution of carbon complexity, ACS Earth

Space Chem., 8(5), 2024, pp.798–856.

[42] L.Snyder and D. BUHL,. Interstellarm

methylacetylene and Isocyanic acid. Nature

Physical Science, 243, 1973, pp.45–46.

Contribution of Individual Authors to the

Creation of a Scientific Article (Ghostwriting

Policy)

The author contributed in the present research, at all

stages from the formulation of the problem to the

final findings and solution.

Sources of Funding for Research Presented in a

Scientific Article or Scientific Article Itself

BMS Education Services Company

Conflict of Interest

The authors have no conflicts of interest to declare.

Creative Commons Attribution License 4.0

(Attribution 4.0 International, CC BY 4.0)

This article is published under the terms of the

Creative Commons Attribution License 4.0

https://creativecommons.org/licenses/by/4.0/deed.en

_US

WSEAS TRANSACTIONS on BIOLOGY and BIOMEDICINE

DOI: 10.37394/23208.2024.21.26

Nigel Aylward

E-ISSN: 2224-2902

259

Volume 21, 2024