SEARCH OF SENSITIZER TO PEPTIDE NUCLEIC ACID SEQUENCE WITH ADENINE AND
GUANINE BASES
J. Tamuliene1, M. L. Balevicius2
1

Institute of Theoretical Physics and Astronomy of Vilnius University, A. Gostauto 12, LT-01108 Vilnius,
Lithuania
Vilnius University, Sauletekio al. 9, III rumai, LT-10222 Vilnius, Lithuania(Received February 24, 2006 Accepted May 30, 2006)

Abstract
Quantum mechanical investigations were performed
to find a suitable sensitizer to peptide nucleic acid(PNA) monomer with Adenine and Guanine basis. It
was shown that interaction of the orbitals of the isolated
PNA sequence with Adenine-Guanine and isolatedsensitizer should be present. It was found that the 3(N,N-dimethyl)-6-(N’-acetilaminel-N’-methyl)
acridindiamine molecule could be used as a sensitizer.
Keywords: peptide nucleic acids (PNA), sensitizer,charge transfer, self-replicating.
1. Introduction
Recently, Rassmunsen et al. designed a protoorganism inspired by the original concepts for a protocell by Luisi and coworkers. This model was different
from the other ones because the authors did not startwith a self-replicating container or a self-replicatinggene, which was later combined and, the mostimportant, instead of RNA peptide nucleic acids (PNA)
were applied [1,2].
The PNA molecule may much easier to couple withthe lipid layer than RNA due to its hydrophobic
backbone and which is also easier to synthesize. On theother hand, the replication of the lipid aggregate isdetermined by the PNA, and it is capable of using PNA
as a genomic code to guide the replication of surfactant
assemblies.
The three functional structures (container,metabolism, and genes) arethermodynamicallycoupled in the proto-organism. The functionalities ofthe proposed proto-organism (to evolve, to selfreproduce, to metabolize, to be adaptive in response toenvironmental changes, and ability to die) are generated
as the different components of this assemble. In thisproto-organism each of the functionalities successively
as they are generated (by the assembly of moresubsystems), under the conditions that each earlier
functionality is a prerequisite of the next following
functionality. It implies, that proto-container is used
before a redox driven proto-metabolism, and further theproto-genes require the proto-metabolism to exist. This
proposed
photo-driven metabolism requires aparticular electron relay chain to function properly, andthis electron relay is implemented within the templating
polymers.
In the above-mentioned proto-organism, thesynthesis of a 1,4-bis(N,N-dimethylamino)naphthalene
sensitizer attached to PNA monomer took place. It isdone to increase the quantum efficiency because thesensitizer coupled with an electron relay system. In thiscase the sensitizer could be introduced to block backthe electron transfer process, and thus the increase theViva Origino 34 (2006) 112 - 115© 2006 by SSOEL Japan

quantum yield of surfactant production. The energizedsensitizer causes a charge separation between thesensitizer and lipid precursor. The neutralization of thesensitizer by the delivery of an electron from the PNA
electron relay chain is occurred. The precursor lipid
molecule is energized and will eventually break into alipid (carboxyl acid) and a phenyl group. However,since no adenine-sensitizer-guanine complex isavailable the replication process will start with theformation of functional PNA dimer consisting of boththe thymine-sensitizer-cytosine and adenine-guaninecomplexes. So, when the sensitizer to PNA sequencewith adenine and guanine (AG) bases is found, theprocess of the self-replication would be simplified (notnecessary the above dimer formation) and it will speed
up the sensitization process for the photo fragmentation
reaction and as a consequence the quantum yield of
surfactant production increased.
Thus, the question arises how and which sensitizer
is better to be attached to PNA oligomer with adenine guanine bases so that quantum efficiency should be as
high as possible and how to simplify the appropriate
sensitizer search.
It was assumed that the selection of the sensitizers
could be performed basing on the relative position of
the eigenvalues of the isolated sensitizer and lipid
molecules. The orbital interaction strongly influences
the quantum efficiency of proto-metabolic process
proposed by Rassmunsen et al. as in the case of
sensitizer search to the PNA sequence with cytosine
and thymine [3-8]. It implies, that the HOMO of asensitizer molecule must be higher than that of lipid
and the same for the LUMO placement of thismolecules. However these conditions are not enoughwhen the sensitizer is searched to the PNA sequencewith A and G. Without going into details, we may statethat the interaction (coupling) of sensitizer orbital with
one of the PNA sequence with adenine and guanine isimportant in this case. The obtained performances arein agreement with these predictions.
2. Computational methodology
The quantum chemical ab initio Hartree-Fock (HF)
and density functional theory (DFT) investigations
were applied with the geometry optimization to gain
structural information on the investigated compounds[8-14]. Geometrical and electronic structures of thesingle photo-donor molecules substituted by a specificgroup to provide an attachment of the molecule to a
PNA fragment with the AG bases to propose as asuitable sensitizer and a lipid molecule wereinvestigated applying B3LYP exchange-correlation
functional with 6-311G** basis set [15, 16] (Fig. 1).

- 112 -

Viva Origino 34 (2006) 112 - 115

Fig. 1 The view of the molecules underinvestigations substituted by bridge fragment. On
the left, the views of the 8-acetilaminomethyl1,4,5,8-tetra hidro-1,2,4,5,6,8-heksaazaantracene(called as I) and on the right 3-(N,N-dimetyl)-6(N’-acetilaminel-N’-metyl)
akridindiamine
molecule (II).

As it was mentioned above, there was assumed, that
selection of the sensitizer could be based on theinvestigation of the relative positions of eigenvalues
and their interaction. Firstly, we tray to find theexplanationwhy
the1,4-bis(N,Ndimethylamino)naphthalene molecule selected assensitizer for the PNA sequence with thymine-cytosine(TC) bases is not suitable in the case of adenine guanine one. The study of the relative positions of theeigenvalues indicates the interaction LUMO+1 of thelipid molecule and the LUMO of the PNA sequencewith A and G. (Fig. 2). Due to the interactions, theseorbitals split and mix in the compound consisting of thelipid molecule and the PNA sequence with AG.
Therefore the LUMO of the above compound could beoriginated from the orbitals of the lipid and PNA
sequence with AG and it could be the reason theabsence of charge transfer from the PNA sequence tolipid despite the necessities for self-replication
processes proposed by Rassmunsen et al. Due to it thequantum efficiency of proto-metabolic process would
be very low. Thus, it was assumed that the above
orbital interaction should be avoided. Following theline of thought it is predicted that the sensitizer for thePNA sequence with A and G bases should be chosen inaccordance with these criteria:
1) the HOMO of a sensitizer molecule must behigher than that of lipid one;2) the LUMO of the lipid would be lower than thatof the PNA sequence with AG and sensitizer;
3) the orbitals of the PNA sequence with A and Gshould (or lipid) interact with the orbitals ofsensitizer.

Fig. 2. The placement of the molecular orbitals of
the lipid, PNA sequence and the molecules thatare under investigations. The HOMO (H) andLUMO (L) of the investigated derivatives aremarked.

investigated two molecules 8-acetylaminomethyl1,4,5,8-tetrahydro-1,2,4,5,6,8-hexaazaanthracene and3-(N,N-dimethyl)-6-(N’-acetylamino-N’methyl)acrydyndiamine that in our notation are called I
and II to simplify discussion (Fig.1). The molecules arechosen not-accidentally because the investigatedmolecule orbitals interact differently with orbital ofPNA sequence. It is necessary to mention that orbitalsof the I molecule interact with the orbitals of the PNA
sequence in the resonance manner of the lipid one,while LUMO of II molecule interact slightly with
LUMO of lipid (Fig.2). It is noted, that the placementof LUMO and HOMO of the selected sensitizers withrespect to of lipid of those is satisfied, i.e. the HOMO
and LUMO of sensitizer are higher than that of lipid
respectively.
In order to obtain more results to confirm ourassumptions the above-mentioned molecules werejoined to PNA fragment with a adenine and guaninebases (Fig.3)

Without going into the theoretical and formal
details here the essence of the third step is very
important because due to the above orbital interaction
these orbitals split and mix in the compound consistingof the sensitizer attached to the PNA sequence with AG.
It leads to avoiding of the orbital interaction of lipid
and the PNA sequence. Therefore it is more probablethat in the PNA with A-sensitizer-G and lipid theHOMO will be mostly originated from atomic orbital ofPNA sequence while the LUMO one will be generally
depicted from the atomic orbital of the lipid. Hence, it
is possible to predict that the self-replication processes
proposed by Rassmunsen et al. will occur.
To place the sign problem in a better perspective we- 113 -Fig. 3. The view of the PNA sequence with
Adenine and Guanine bases. The number marks
the position where sensitizer could be connect
to this sequence.

Viva Origino 34 (2006) 112 - 115

To obtain the geometrical structure of the molecule assensitizer (S) attached to the PNA with A and G bases,
the HF method with 6-31G basis set was applied. Thesensitizer molecule was attached to the PNA sequencein the position that was obtained in the case of PNA
sequence with Thymine and Cytosine. In this case thesensitizer is attached near Guanine (Figs. 3, 4) [17-20].
The geometry optimization was performed by HF/631G. In order to obtain more accurate results moreelaborate ab initio treatment such as DFT, MP2 and thesimilar are required, but this requires too muchcomputation resources for such large molecules withC1 molecular symmetry. On the other hand, ourinvestigation of the PNA sequence with cytosine baseand lipid molecule indicates, that the geometry of suchkind compounds obtained by DFT and HF approachcoincide enough well and most important, obtained
performances are in agreement with an experiment [8].
Additionally, it is shown that HF calculations agree
well with the experimental bond lengths and very wellwith angles [21]. Hence, the HF approach is used to
avoid too large computational time and memory
resources. The nature of molecular orbitals andtransitions will be evaluated applying GUGA/6-31G
method. It is remarkable, that in this paper we
presented only the successful cases of our investigatedsensitizers excluding others which were worse from thequantum mechanical point of view.

Fig. 4. The view of structures of the investigatedcompound consist of the lipid and the PNA
sequence with A and G basis substituted by II
molecule to exhibit where the sensitizer isconnected more properly. The views of theinvestigated compound are possible to see in Fig.5and 6 also.

appropriate to say, that the HOMO-LUMO transition
should be forbidden and correspond to transition fromsensitizer to lipid.
Guided by analogy, one might guess that the II
investigated molecule is not suitable sensitizer. Theconclusion is based on the investigation of the HOMO
and LUMO nature of the compound consisting of lipid
and the PNA sequence with A and G bases substituted
by sensitizer (see Fig. 5).
In our described case the HOMO and LUMO ofthe above compounds consist of the π orbitals of
sensitizer mostly (Fig. 5). Hence, it is more appropriate
to say that allowed transition should be obtained fromHOMO to LUMO that leads to charge redistribution
only, i.e. the charge transfer to lipid due to vibration
and rotation absent.
We would like to point out that the describedsituation is not conventional for self-replication process
although not fully conclusive because the otherphenomenon is omitted in this work, but it could
influence to this process also. Let us remember, that inthis case the both sensitizer and lipid LUMO interact.
Consequently, the choosing sensitizer is not correct if
one makes the assumption that the lipid and sensitizer
orbitals should interact.
Completely different situation arise in the case ofthe I molecule. Let us remember that orbital of thismolecule interact with one of the PNA sequence withAG. In this case the HOMO of the compound (lipid,the PNA sequence with A and G bases joined with I) is
described by the atomic orbital of the sensitizer atoms
while the LUMO one consist of the atomic orbital ofcertain atom of the lipid (Fig. 6).
The nature of HOMO-LUMO orbitals and theirplacement allow us to foresee that the HOMO-LUMO
transition should be forbidden and correspond totransition from sensitizer to lipid. Roughly speaking,we have situation that is necessary for the describedself-replication processes. Although not fully described
the charge transfer in the compound the comparing
performances of the investigations of the PNA
sequence with cytosine and thymine bases and the PNA
sequence with guanine and adenine bases conclude that

3. Obtained performance
The primary purpose of these investigations to findthe sensitizer to PNA sequence with Adenine andGuanine because of potential application in the selfreplication processes. In an effort to shed light on thesubject, the investigation of the compounds consistingof lipid precursor molecule and the PNA sequence with
AG and sensitizer is performed. The above mentioned
compounds with a lipid precursor are investigated to
guide the excited charge transfer. Several aspects ofthis purpose deserve special comment following from
our investigation described in [8]: 1) during photoexcitation the charge redistribution in the PNA
fragment should take place and then the charge isslowly transferred to lipid, and 2) later it is transfered tosensitizer due to rotation and vibrations. It is moreFig. 5. Molecular orbitals of the compoundconsist of the lipid and the PNA sequence withA and G basis substituted by II molecule.

- 114 -Viva Origino 34 (2006) 112 - 115

Fig. 6. Molecular orbitals of the compound consistof the lipid and the PNA sequence with A and G
basis substituted by I molecule. In this case themolecule is joined to the PNA sequence with A
and G near Adenine basis.

the I molecule could be applied as sensitizer. The
sensitizer coupled with an electron relay system andcould be introduced to block back the electron transferprocess. Hence, - the quantum yield of surfactant
production will be increased. On the other hand ourprediction that the sensitizer to the PNA sequence with
A and G basis should be chosen so that these molecule
orbitals interact is confirmed also.
4. Conclusions
Basing on the investigation results it is evident thatthe account of the relative positions of single molecule
orbital and their interaction help us in the selection of
the sensitizer for the PNA sequence with A and G bases.
The comparison investigation performances of the PNA
sequences with both AG and TC basis allow us toconclude that I molecule (8-acetylaminomethyl-1,4,5,8tetrahydro-1,2,4,5,6,8-hexaazaanthracene) could beapplied as sensitizer to this sequence with A and Gbasis. So the self replication process is simplified. The
choosing of the sensitizer joined to the PNA sequencewith Adenine and Guanine bases should be performedin accordance with these criteria:
1) the HOMO of a sensitizer molecule must be
higher than that of lipid one;2) the LUMO of the lipid would be lower than thatof the PNA sequence with AG and sensitizer;
3) the orbital of the PNA sequence with A and G(interacting with that of lipid) should also interactwith orbitals of sensitizer.
Acknowledgments
The work was funded via PACE (Programmable
Artificial Cell Evolution), European Integrated Projectin the EU FP-6-IST-FET Complex Systems Initiative”
and partly by Lithuanian State Science and Studies
Foundation. We are grateful to Supercomputing centerof Vilnius Technical University and and B.G.M. Ltd.
(Vilnius, Lithuania) for the possibility to use cluster
and GAMESS package.

References
1. Luisi, L., Giomini, M., Pileni, M. and Robinson, B. Reverse
micelles as hosts for proteins and small molecules, Biochim.
Biophys. Acta 947, 209-246 (1988).
2. Morowitz, H., Deamer, D. and Heinz, B. The chemical logic of aminimum protocell, Orig. Life Evol. Biosph. 18, 281-287 (1988).
3. Rassmunsen, S., Chen, L., Nisson, M. and Abe, S. Bridging
nonliving and living matter, Artificial Life 9, 267-316 (2003).
4. Apel, C., Deamer, D. and Mautner, M. Self-assembled vesicles ofmonocarboxylic acids and alcohols: conditions for stability and forthe encapsulation of biopolymers, Biochim Biophys. Acta 1559, 19 (2002).
5. Nielsen, P. Peptide nucleic acid (PNA): a model structure for theprimordial genetic material?, Orig. Life Evol. Biosph.23, 323-327(1993).
6. Luisi, P. L., Walde, P. and Oberholzer, T. Ber. Bunsenges,
Enzymatic RNA Synthesis in Self- Reproducing Vesicles: An
Approach to the Construction of a Minimal Synthetic Cell, Phys.
Chem. 98, 1160-1165 (1994).
7. Von Kiedrowski, G. Minimal replicator theory I: Parabolic versus
exponential growth, Bioorganic chemistry frontiers, 3, 115-146,(1993).
8. Tamuliene, J. and Tamulis, A. Quantum mechanical investigationsof self-assembled system consisting of peptide nucleic acid,sensitizer, and lipid precursor molecules, Lithuanian J. Phys. 45,
167-174 (2005).
9. McWeeny, R. and Dierksen, G. Self-consistent perturbation theory.
II. Extension to open shells, J. Chem. Phys. 49, 4852 -4856(1968).
10. Becke, A. D., J. Density-functional thermochemistry. . The roleof exact exchange, Chem. Phys. 98, 5648-5652 (1993).
11. Miehlich, B., Savin, A., Stoll, H. and Preuss H. Results obtainedwith the correlation energy density functionals of Becke and LeeYang and Parr, Chem. Phys. Lett. 157, 200-206 (1989).
12. Lee, C., Yang, W. and Parr, R. G. Development of the ColleSalvetti correlation-energy formula into a functional of theelectron density, Phys. Rev. B, 37, 785-789 (1988).
13. Perdew, J. P., Burke, K. and Wang, Y. Generalized gradientapproximation for the exchange-correlation hole of a manyelectron system, Phys. Rev. B 54, 16533-16539 (1996).
14. Perdew, J. P., Chevary, J. A., Vosko, S. H., Jackson, K. A.,
Pederson, M. R., Singh, D. J. and Fiolhais, C. Erratum: Atoms,molecules, solids, and surfaces: Applications of the generalized
gradient approximation for exchange and correlation, Phys. Rev. B,48, 4978 (1993).
15. Burke, K., Perdew, J. P. and Wang, Y. Electronic Density
Functional Theory: Recent Progress and New Directions, Ed. J. F.
Dobson, G. Vignale, and M. P. Das , Plenum, 1998.
16. Krishnan, R., Binkley, J. S., Seeger, R. and Pople, J. A. Selfconsistent molecular orbital methods. XX. A basis set forcorrelated wave functionsJ. Chem. Phys. 72, 650-654 (1980).
17. Clark, T., Chandrasekhar, J., Spitznagel, G. W. and Schleyer, P. v.
R. Efficient Diffuse Function-Augmented Basis Sets for Anion
Calculations.III The 3-21+G Basis Set for First- Row Elements,Li-F, .J. Comp. Chem. 4, 294-301 (1983).
18. Rassolov, V. A, Ratner, M. A., Pople, J. A., Redfern, P. C. andCurtiss, L. A. 6-31G*Basis Set for Third-Row Atoms, J. Comp.
Chem. 22, 976-984 (2001).
19. McLean, A. D. and Chandler, G. S. Contracted Gaussian basis setsfor molecular calculations. I. Second row atoms, Z 11-18., J. Chem.
Phys., 72, 5639-5648 (1980).
20. Rassolov, V. A., Pople, J. A, Ratner, M. A. and Windus, T. L. 631G* Basis Set for Atoms K through Zn, J. Chem. Phys. 109,1223-1229 (1998).
21. Martinez-Merino,V. and Gil, M. J. Modeling of tautomerism ofpyridine-2(1H)-thione from vapor to solution, J. Chem. Soc.,
Perkin Trans. 2, 801-806 (1999).

- 115 -