The Headgroup (A)Symmetry Strongly Determines the Aggregation Behavior of Single-Chain Phenylene-Modified Bolalipids and Their Miscibility with Classical Phospholipids

Drescher, Simon; Lechner, Bob Dan; Garamus, Vasil M.; Almásy, László; Meister, Annette; Blume, Alfred

doi:10.1021/la501160s

Cited by 24 publications

(47 citation statements)

References 52 publications

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“…This behaviour indicates the formation of nanofibres, which in turn immobilize the solvent molecules and allow the formation of a transparent hydrogel. A similar observation was found for PC-C17pPhC17-PC [35] and also for phenylene-free analogues, such as PC-Cn-PC with alkyl chain lengths ranging from n = 22–36 [24–26 38,40]. …”

Section: Resultssupporting

confidence: 80%

“…The results obtained were compared to PC-C17pPhC17-PC [35] and PC-C16pPhC16-PC [36], structural analogues with slightly shorter alkyl chains, and the homologous series of phenylene-free PC-Cn-PC, with n = 22–36 [24–26 38,40]. …”

Section: Resultsmentioning

confidence: 99%

“…Both transition temperatures in the DSC heating scan are about 5 K higher compared to T m -values of the lipid analogue PC-C17pPhC17-PC with a slightly shorter alkyl chain (two methylene units) [35]. The increase in T m is caused by the elongation of the alkyl chain, which leads to an increase in van-der-Waals contacts of neighbouring bola molecules.…”

Section: Resultsmentioning

confidence: 99%

“…Besides heteroatoms [29–30], acetylene [31] or diacetylene groups [32], or methyl branches [31,33], also phenyl- or biphenyl rings were inserted into the long alkyl chain [34–37]. The insertion of a phenylene group led to PC-C16pPhC16-PC [36], which self-assembles at room temperature into small ellipsoidal micelles, and to PC-C17pPhC17-PC [35] that forms nanofibres with a significantly reduced thermal stability compared to PC-C32-PC. Unfortunately, the insertion of PC-C17pPhC17-PC into phospholipid bilayers composed of, e.g .…”

Section: Introductionmentioning

confidence: 99%

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Aggregation behaviour of a single-chain, phenylene-modified bolalipid and its miscibility with classical phospholipids

Drescher¹,

Garamus

Garvey³

et al. 2017

Beilstein J. Org. Chem.

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In the present work, we describe the synthesis of a single-chain, phenylene-modified bolalipid with two phosphocholine headgroups, PC-C18pPhC18-PC, using a Sonogashira cross-coupling reaction as a key step. The aggregation behaviour was studied as a function of temperature using transmission electron microscopy (TEM), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, and small angle neutron scattering (SANS). We show that our new bolalipid self-assembles into nanofibres, which transform into flexible nanofibres at 27 °C and further to small elongated micelles at 45 °C. Furthermore, the miscibility of the bolalipid with bilayer-forming phosphatidylcholines (DMPC, DPPC, and DSPC) was investigated by means of DSC, TEM, FTIR, and small angle X-ray scattering (SAXS). We could show that the PC-C18pPhC18-PC is partially miscible with saturated phosphatidylcholines; however, closed lipid vesicles with an increased thermal stability were not found. Instead, bilayer fragments and disk-like aggregates are formed.

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Section: Resultssupporting

confidence: 80%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Aggregation behaviour of a single-chain, phenylene-modified bolalipid and its miscibility with classical phospholipids

Drescher¹,

Garamus

Garvey³

et al. 2017

Beilstein J. Org. Chem.

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“…Recently, we showed that the headgroup asymmetry strongly influences the aggregation behavior of single-chain bolalipids. 32,33 The new bolalipids contain a membrane-spanning C32 alkyl chain that is bound with one end to the sn-3 position of a glycerol unit whereas the other end carries only a hydroxyl group. The sn-2 position of the glycerol moiety is etherified with either a hexadecyl (lipid I) or a racemic 10-methylhexadecyl (lipid II) residue ( Figure 1).…”

Section: ■ Introductionmentioning

confidence: 99%

Highly Asymmetrical Glycerol Diether Bolalipids: Synthesis and Temperature-Dependent Aggregation Behavior

et al. 2015

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In the present work, we describe the synthesis and temperature-dependent aggregation behavior of two examples of a new class of highly asymmetrical glycerol diether bolaphospholipids. The bolalipids contain a long alkyl chain (C32) bound to glycerol in the sn-3 position, carrying a hydroxyl group at the ω position. The C16 alkyl chain in the sn-2 position either possesses a racemic methyl branch at the 10 position of the short alkyl chain (lipid II) or does not (lipid I). The sn-1 position of the glycerol is linked to a zwitterionic phosphocholine moiety. The temperature-dependent aggregation behavior of both bolalipids was studied using differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, and X-ray scattering. Aggregate structures were visualized by transmission electron microscopy (TEM). We show that both bolalipids self-assemble into large lamellar sheetlike aggregates. Closed lipid vesicles or other aggregate structures such as tubes or nanofibers, as usually found for diglycerol tetraether lipids, were not observed. Within the lamellae the bolalipid molecules are arranged in an antiparallel (interdigitated) orientation. Lipid I, without an additional methyl moiety in the short alkyl chain, shows a lamellar phase with high crystallinity up to a temperature of 34 °C, which was not observed before for other phospholipids.

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Phenylene bolaamphiphiles: Influence of the substitution pattern on the aggregation behavior and the miscibility with classical phospholipids

Drescher

Meister²,

Garamus

et al. 2014

Euro J Lipid Sci & Tech

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The synthesis of two symmetric single‐chain phenylene‐modified bolaamphiphiles with meta and ortho phenyl substitution pattern is described. The aggregation behavior of both bolaamphiphiles in aqueous suspension was investigated by differential scanning calorimetry (DSC), transmission electron microscopy (TEM), Fourier‐transform IR (FTIR) spectroscopy, and small angle neutron scattering (SANS). We could show that a change in the substitution pattern from para to meta or ortho leads to a change in the aggregation behavior so that small micelles instead of nanofibers are formed. Furthermore, the mixing behavior of these bolaamphiphiles with classical bilayer forming phospholipids, such as 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine (DPPC) and 1,2‐distearoyl‐sn‐glycero‐3‐phosphocholine (DSPC) was studied by means of DSC, TEM, cryo‐TEM, and small angle X‐ray scattering (SAXS). The aim was to stabilize bilayer membranes formed by classical phospholipids by incorporation of bolaamphiphiles to obtain liposomes with improved stability suitable for drug delivery purposes. We could show that the phenylene‐modified bolaamphiphiles are indeed miscible with DPPC and DSPC; however, closed vesicles as observed for pure DPPC and DSPC were not found. Instead, small disk‐like aggregates are formed. In the case of mixtures of phenylene‐modified bolaamphiphiles with DPPC, these bilayer disks have a higher DSC transition temperature compared to pure DPPC indicating an increased stability of the ordered gel phase inside the disks. Practical applications: Vesicles composed of classical phospholipids are widely used as drug delivery systems for pharmaceutical applications. The stability of these vesicles in, e.g., body fluids is an important prerequisite for long‐term applications and it can possibly be enhanced by the incorporation of bipolar amphiphiles (bolaamphiphiles) into phospholipid bilayers. With the use of novel single‐chain phenylene‐modified bolaamphiphiles, synthesized in this work, we are able to generate small lipid‐disks in mixtures with classical phospholipids that have an increased stability of the ordered gel phase inside these disks compared to pure phospholipids. These disks might be further used as nano‐dimensioned drug carrier systems. The incorporation of ortho‐substituted phenylene‐modified bolaamphiphiles (PC‐C17oPhC17‐PC) into DPPC bilayer leads to the formation of small disk‐like aggregates with an increased stability compared to pure DPPC vesicles.

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The Headgroup (A)Symmetry Strongly Determines the Aggregation Behavior of Single-Chain Phenylene-Modified Bolalipids and Their Miscibility with Classical Phospholipids

Cited by 24 publications

References 52 publications

Aggregation behaviour of a single-chain, phenylene-modified bolalipid and its miscibility with classical phospholipids

Aggregation behaviour of a single-chain, phenylene-modified bolalipid and its miscibility with classical phospholipids

Highly Asymmetrical Glycerol Diether Bolalipids: Synthesis and Temperature-Dependent Aggregation Behavior

Phenylene bolaamphiphiles: Influence of the substitution pattern on the aggregation behavior and the miscibility with classical phospholipids

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