Nucleolipids as potential organogelators

Article abstract of DOI:10.1080/15257770701508521

Four different series of nucleolipids or bola-nucleolipids were synthesized or re-synthesized. Most of the compounds were studied with respect to their gelation properties toward either water or aromatic, hetero-aromatic, and aliphatic hydrocarbons. Bola-nucleolipids 6 and 7 do not gelate any solvent tested, neither as sole additive nor by adding up to 10 wt% of a 1:1 mixture. The nucleolipid 22 carrying the antiviral acyclovir as a head group proved to be a potent organogelator for aromatic hydrocarbons such as toluene, but not for hetarenes, aliphatic hydrocarbons or water. The mono-tailed nucleolipid 24 exhibits excellent organogelator properties for both aromatic and aliphatic hydrocarbons. These were studied as a function of concentration and temperature. Copyright Taylor & Francis Group, LLC.

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Nucleolipids as Potential Organogelators
Helmut Rosemeyer a , Eva-Maria Stürenberg a & Piet Herdewijn b
a Organische Chemie I—Bioorganische Chemie, Institut für Chemie,
Universität Osnabrück, Osnabrück, Germany
b Katholieke Universiteit Leuven, Department Farmaceutische
Wetenschappen, Afd. Medicinale Chemie, Leuven, Belgium
Version of record first published: 10 Dec 2007
To cite this article: Helmut Rosemeyer, Eva-Maria Stürenberg & Piet Herdewijn (2007): Nucleolipids as
Potential Organogelators, Nucleosides, Nucleotides and Nucleic Acids, 26:8-9, 995-999
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Nucleosides, Nucleotides, and Nucleic Acids, 26:995–999, 2007
Copyright ꢀ Taylor & Francis Group, LLC
C
ISSN: 1525-7770 print / 1532-2335 online
DOI: 10.1080/15257770701508521
NUCLEOLIPIDS AS POTENTIAL ORGANOGELATORS
Helmut Rosemeyer and Eva-Maria Stu¨ renberg
Organische Chemie
2
I — Bioorganische Chemie, Institut fu¨r Chemie, Universita¨t Osnabru¨ck, Osnabru¨ck,
Germany
Piet Herdewijn
Katholieke Universiteit Leuven, Department Farmaceutische
2
Wetenschappen, Afd. Medicinale Chemie, Leuven, Belgium
Four different series of nucleolipids or bola-nucleolipids were synthesized or re-synthesized. Most
2
of the compounds were studied with respect to their gelation properties toward either water or aro-
matic, hetero-aromatic, and aliphatic hydrocarbons. Bola-nucleolipids 6 and 7 do not gelate any
solvent tested, neither as sole additive nor by adding up to 10 wt% of a 1:1 mixture. The nu-
cleolipid 22 carrying the antiviral acyclovir as a head group proved to be a potent organogelator
for aromatic hydrocarbons such as toluene, but not for hetarenes, aliphatic hydrocarbons or water.
The mono-tailed nucleolipid 24 exhibits excellent organogelator properties for both aromatic and
aliphatic hydrocarbons. These were studied as a function of concentration and temperature.
Keywords Organogelator; nucleolipid; gelation properties
INTRODUCTION
Nucleolipids are hybrid molecules composed from a nucleobase, a
nucleoside, a nucleotide or a nucleic acid (either DNA or RNA) and a
lipophilic moiety which might be either a single- or double-chained alkyl
(or alkenyl) chain or a carbocyclic hydrocarbon such as cholesterol, a vita-
min, or a bile acid.
Various nucleoside chemotherapeutics such as 1-ß-D-arabinofuranosyl-
cytosine, -adenine, -7-deazaadenine, and -5-fluorouracil have been con-
nected to various lipids by chemical means and are applied as
pharmacologically active derivatives with enhanced catabolic stability and
activity compared to the parent compounds.[1]
This work was financially supported by the research pool of the University of Osnabru¨ck and by the
Francqui Fond, Belgium.
Address correspondence to Helmut Rosemeyer, Organische Chemie I — Bioorganische Chemie,
Institut fu¨r Chemie, Universita¨t Osnabru¨ck, Barbarastr. 7, D-49069 Osnabru¨ck, Germany. E-mail:
Helmut.Rosemeyer@uos.de.
995

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H. Rosemeyer et al.
SCHEME 1
RESULTS AND DISCUSSION
In the beginning of our study we have synthesized or resynthesized sev-
eral bola-nucleolipides (6, 7, 15, 18, 22, 24) (Schemes 1 and 2) and have
studied most of them with respect to their gelation properties toward either
water or aromatic, heteroaromatic and aliphatic hydrocarbons.[1,2]
The synthesis of the bisuridylic acid derivative 6[31P-NMR (D2O/TRIS-
HCl): 9.02 ppm] was carried out according to Iwaura et al.[2] The
bisadenylic acid derivative 7[31P-NMR (D2O/TRIS-HCl): 9.20 ppm] was pre-
pared analogously starting from the corresponding benzoyl-protected phos-
phoramidite of 2ꢁ-deoxyadenosine. Contrary to the fact that for compound
6 hydrogelation properties were reported,[2] we have demonstrate that

Nucleolipids as Potential Organogelators
997
SCHEME 2
neither 6 nor 7 do gelate any solvent tested, neither as sole additive nor
by adding up to 10 wt% of an equimolar mixture.
Following the route presented on Scheme 2 bola-nucleolipids such as
15 and 18 carrying a dotriacontane spacer were prepared via compounds 13
and 16.[3,4] Studies on their gelation properties are under way.
The nucleolipid 22 (Scheme 3), carrying the antiviral acyclovir as head
group,[1] proved to be a potent organogelator for aromatic hydrocarbons
such as toluene, but not for hetarenes, aliphatic hydrocarbons or water.
Such nucleolipids with other pharmacologically active head groups might
be useful, e.g. for the topical treatment of skin deseases bringing about their
own pharmaceutical formulation (ger.: Galenik).

998
H. Rosemeyer et al.
TABLE 1 Gelator properties of 24 in various solvents as a function of concentration
Conc. of 24 (w-%)
Benzene
Decane
Hexane
Toluene
5
2
1
G
G/V
L
G
G
V
G
G
L
G
V
L
G: gel; V: viscous; L: soluble.
TABLE 2 Gelation properties of 24 in various solvents as a function of temperature
Temp. [◦C]
Benzene
Decane
Hexane
Toluene
10
r.t.
30
40
50
G
G
G
G
V
G
G
G
G
G
G
G
G
V
L
G
G
V
L
L
SCHEME 3
SCHEME 4
The mono-tailed nucleolipid 24 (Scheme 4) exhibits excellent organo-
gelator properties for both, aromatic as well as aliphatic hydrocarbons[1]
Tables 1 and 2 summarize these properties as a function of concentration
and temperature.

Nucleolipids as Potential Organogelators
999
REFERENCES
1. Rosemeyer, H. Nucleolipids: Natural occurance, synthesis, molecular recognition, and supramolec-
ular assemblies as potential precursors of life and bioorganic materials. Chemistry & Biodiversity 2005,
2, 977–1062; and literature cited therein.
2. Iwaura, R.; Yoshida, K.; Masuda, M.; Ohnishi-Kameyama, M.; Yoshida, M.; Shimizu, Z.
Oligonucleotide-templated self-assembly of nucleotide bolaamphiphiles: DNA-like nanofibers
edged by a double-helical arrangement of A-T base pairs. Angew. Chem. 2003, 115, 1039–1042.
3. 13: H-NMR (CDCl3): δ = 3.38 (t, CH2Br); 1.86 (t, CH2-CH2Br); 1.43 (m, CH2-CH2-CH2Br); ∼ 1.25
(m, CH2). 13C-NMR (CDCl3): δ = 134.1 (CH2Br); 32.8 (CH2-CH2Br); ∼ 29 (multiple C); ∼ 28 (mul-
tiple C). 16: 1H-NMR (CDCl3): δ = 3.44 (t, CH2OH); 1.32 (t, CH2-CH2OH); 1.31 (m, CH2). 13C-
NMR (CDCl3): δ = 63.2 (CH2OH); 32.8 (CH2-CH2OH); 29.6 (CH2); 29.4 (CH2-CH2-CH2OH);
25.7 (CH2).
4. Mohr, W.; Horn, C. R.; Stahl, J.; Gladysz, J.A. convenient and convergent syntheses of long chain
α,ω-dibromides and diphosphines of the formula X(CH2)nX (n = 18–32). Synthesis 2003, 1279–
1285.