Bolaamphiphile vesicle membrane

There are, for example synkinons for the synkinesis of micelles, vesicles, pores, fibres and planar mono- or multilayers. A given synkinon can also be applied for another synkinetic target if the conditions are changed or if the synkinon is chemically modified. The most simple example is stearic acid. At pH 9, it is relatively well-soluble in water and forms spherical micelles. If provided with a hydrogen bonding chiral centre in the hydrophobic chains (12-hydroxystearic acid), it does not only form spherical micelles in water but also assembles into helical fibres in toluene. At pH 4, stearic acid becomes water-insoluble but does not immediately crystallize out spherical vesicles form. A second type of synkinon, which produces perfectly unsymmetrical vesicle membranes, consists of bolaamphiphiles with two dififerent head groups on both ends of a hydrophobic core. Such bolaamphiphiles are also particularly suitable for the stepwise construction of planar multilayered assemblies. 

Figure 4.5 A small part of a monolayered vesicle membrane made by a one-sided precipitation of the given bipyridinium bolaamphiphile 2 with perchlorate.

The immisdbility of CF2- and CHi-chains was also utilized for the preparation of unsymmetric vesicle membranes. The hydrophobic parts of bolaamphiphile 5 with fatty acid and fluorocarbon sulfonate halves do not mix and all the fluorosulfonate halves were on the outer side of the monolayered vesicle membrane (Figure 4.7). The sulfonate head group was once more localized by the metachromatic effect, the hydrophobic parts with F- and H-substituted spin labels. 

Figure 4.6 a) The bolaamphiphile 3 with a large and a small head group assembles to form asymmetric vesicle membranes. 

Similar results were obtained when the zinc porphyrin was bound to the outer vesicle surface and a quinone bolaamphiphile was integrated within a DHP or DODAB vesicle membrane. The quenching constant of the porphy-... 

Unlike conventional, one-headed amphiphiles which can readily slither into vesicle membranes as single chains, bolaamphiphiles can only insert themselves into a preformed membrane in the form of loops (Figure 4.19). Bolaamphiphiles with stiff ethylene glycol segments tend to disrupt vesicle membranes and are extremely effective in releasing entrapped dyes, e.g. 5(6)-carboxyfluore-scein. ... 

Figure 4.19 Bolaamphiphiles destabilize bilayer vesicle membranes. ...

Figure 4.24 A monensin-based, dianionic bolaamphiphile assembles to form hydrated ion pores in monolayered vesicle membranes. They can be reversibly closed by a,(xi-diamino bolaamphiphiles. ...

Photoaddition reactions of entrapped bolaamphiphiles should occur regioselectively if both head groups are locked on the inner and outer surface of a vesicle membrane. A detailed study of such a reaction confirmed this pre-... 

Figure 2.5.14 Asymmetrical monolayered vesicle membranes have been obtained from the two bolaamphiphiles shown, (a) All large headgroups are on the outer surface, all small headgroups at the inside of the vesicle. This phenomenon is by no means universal. It has to be tested for each individual asymmetrical bolaamphiphile. In most cases there is only a small difference in the localization of different headgroups. In (b) the metachromatic effect of polyanions on methylene blue aggregation on the sulfonated membrane outside is indicated (see text above).

Figure 2.7.3 A disulfone bolaamphiphile forms vesicles, which are perforated by a tetraamino edge amphiphile containing two carboxylate end groups. The amine presumably occurs in the conformation given. It assembles in vesicle membranes to form pores that let iron(II) ions pass the membrane. Large organic ions close the pore. EDTA in the bulk water phase cannot pass through the pore and sucks iron ions out of the vesicle, (From Fuhrhop et al., 1988.)...

Figure 7.2.3 Static entrapment of a bolaamphiphilic anthraquinone in a vesicle membrane. Light-induced elctron transfer and the dark back-reaction both occur with high speed in this system (within nanoseconds). Surface charge of the vesicle has only a small effect. (From Siggel et al., 1987.)...

The nucleophilic reactivity of cysteine has been exploited in Michael reactions with quinones. One example is a water-soluble naphthoquinone, which has been entrapped in chlorophyll-containing vesicles in order to study light-induced electron transfer through a membrane from glutathione to the quinone (Fore, 1983). Another example is an asymmetrical vesicle membrane made of a cysteine quinone carboxylate bolaamphiphile, where all the quinone is localized on the outer surface of the vesicle (see Scheme 7.2.6 Scheme 9.5.1). 

Fuhrhop, J.-H., Liman, U., Koesling, V. (1988). A macrocyclic tetraether bolaamphiphile and an oligoamino a, -dicarboxylate combine to form monolayered, porous vesicle membranes, which are reversibly sealed by EDTA and other bulky anions, J. Am. Chem. Soc., 110 6840. 

A new family of crown-ether-based bolaamphiphiles, 21, that aggregate into a previously unknown type of bolaamphisome was prepared by Gokel and coworkers [50]. Evidence was presented on vesicle formation from the aqueous suspension of such bolaform amphiphiles. Several reports describing the synthesis of various macrocyclic models related to archael compounds have also appeared in the literature [51]. Fyles et al. prepared a novel series of asymmetric bis-macrocyclic bolaphiles, 22, and evaluated their transport activities in vesicles and planar bilayer membranes [52]. 

Firstly we have to differentiate between monolayer (MLM) and bilayer (BLM) lipid membranes in vesicles. MLMs are composed of bolaamphiphiles these are amphiphiles which carry two head groups, namely one on each end of a hydrophobic core. Two head groups instead of one renders the amphiphile more water-soluble. Two short alkyl chains with 12 or more methylene groups, or one long chain with more than 24 hydrophobic atoms must be employed in order to obtain amphiphiles with a low critical vesicular concentration ( cvc < 10 M). The general abbreviation cmc is, however, usually applied instead of cvc . 

In the MLM and BLM vesicles, the cmc is small (< 10 M). In MLMs, the solubility of the individual monomers may be relatively large, if they contain charged head groups. Once the bolaamphiphiles are entrapped in a vesicular assembly they cannot escape, as the polar head group would have to pass through an apolar membrane, which is an unlikely process. At pH = 9, for example, the diacetic acid la dissolves reasonably well as the dianion in water. 

In nature, asymmetry is achieved through membrane dissolved proteins. In lipid membrane systems without proteins, only monolayers made of bola-amphiphiles allow a totally asymmetric arrangement of head groups. The simplest asymmetry to be achieved is dependent on the one-sided precipitation of bolaamphiphiles. a,to-Dicarboxylic acids, for example, are often soluble at pH > 8 and spontaneously form vesicles upon acidification to pH 5. At a lower pH, all carboxyl groups become protonated and one usually observes ill-defined precipitates . 

Covesicles of the cationic nitrobenzoate 6 and DODAC, or corresponding DPP-analogues, e.g. 7, are hydrolysed at pH 8. Nitrophenolate absorption appears at 400 nm. The outer benzoate esters at the outer vesicle surface are hydrolysed within minutes and the same head groups on the inner surface survive for 1-15 hours (Figure 4.9). Detailed kinetics of flip-flop dynamics and OH permeation have been evaluated in these systems. Monolayer lipid membranes made of macrocyclic bolaamphiphiles showed enhanced dynamic stability. ... 

Figure 4.10 Symmetric vesicles with reactive head groups turn asymmetric when a water-soluble, membrane-inactive reagent reacts only with the outer surface. Flip-flip usually takes hours and can be completely suppressed in MLMs made of charged bolaamphiphiles. 

Photolabelling experiment of a vesicle bilayer membrane with bola-amphiphile DIPEP. The light green areas indicate the membrane portions which would be photolabelled by the diazirine (white circles) upon UV irradiation, if the bolaamphiphile stretched through the membrane was inwardly or outwardly U-shaped. Labelling experiments of the amino groups on the outer surface shows that all three conformations occurred in a statistical ratio. ... 

Recent reports on monomeric and polymerized bolaamphiphiles1 provide evidence for their potential application in the broader field of molecular organizates (1,2). Thus monomeric bolaamphiphiles have been employed in the formation of monolayer lipid membranes or vesicles (1-3). formation of micelles (4-5) and also for spanning bilayer membranes (1-6) The latter process has resulted in the stabilization of membranes. 

Spherical vesicles (see Sec. 2.5.4) are made by the same kind of amphiphiles that form micelles. Highly soluble amphiphiles (e.g., sodium salts of fatty acids or soaps) form micelles badly soluble amphiphiles (e.g., free fatty acids) give vesicles or crystallize. Amphiphilic monomers with two or three long alkyl chains are often totally water insoluble as monomers but dissolve well as vesicular assemblies. Vesicles usually collapse upon drying (Fig. 1.5.8a), but one isolable monolayer vesicle made of rigid carotenoid bolaamphiphiles has also been reported (Fig. 5.5). Hydrogen bond chains convert spherical vesicles to tubules. Such tubules can again be isolated in the dry form and can be stored. They are particularly stable if monolayer membranes are used (Fig. 1.5.8b). 

The potential applications of bolaamphiphiles include the formation of monolayer vesicles for drug/gene delivery, ultra thin monolayer membranes, inclusion of functionalities into membranes, and disruption of biological membranes [59a]. 

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