cavitands - nanochemistry

7/23/2019 cavitands - nanochemistry

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Cavitands, synthetic organic compounds with rigid cavities of molecular dimensions, are extremely

interesting and versatile molecular receptors, the complexation properties of which have been

extensively studied in the solid state, in solution, and in the gas phase.

Examples of cavitands include cyclodextrins, calixarenes and cucurbiturils.

Cyclodextrins

One of the most well-known and extensively studied naturally occurring

macrocycles is the structurally complex oligosaccharides known as cyclodextrin.

Easily obtained from starch (made up of several D-glucose units) with -amylase

enzymes it shows high complexation properties with extensive biomechanical uses with their

somewhat lipophilic central cavity and hydrophilic outer surface.

Due to the chair conformation of the glucopyranose units, the cyclodextrins are shaped like a

truncated cone rather than perfect cylinders. The hydroxyl functions are orientated to the coneexterior with the primary hydroxyl groups of the sugar residues at the narrow edge of the cone and

the secondary hydroxyl groups at the wider edge. The central cavity is lined by theskeletal carbons

and ethereal oxygens of the glucose residues, which gives it a lipophilic character. The polarity of the

cavity has been estimated to be similar to that of an aqueous ethanolic solution. The natural -, -

and -cyclodextrin consist of six, seven, and eight glucopyranose units, respectively.

In aqueous solutions cyclodextrins are able to form inclusion complexes with many drugs by taking

up a drug molecule, or more frequently some lipophilic moiety of the molecule, into the central

cavity. No covalent bonds are formed or broken during thecomplex formation and drug molecules in

the complex are in rapid equilibrium with free molecules in the solution. The driving forces for thecomplex formation include release of enthalpy-rich water molecules from the cavity, electrostatic

interactions, van der Waals interactions, hydrophobic interactions, hydrogen bonding, release of

conformational strain and charge-transfer interactions.

One of the unique properties of cyclodextrins is their ability to enhance drug delivery through

biological membranes. The cyclodextrin molecules are relatively large (molecular weight ranging

from almost 1000 to over 1500), with a hydrated outer surface, and under normal conditions,

cyclodextrin molecules will only permeate biological membranes with considerable difficulty. It is

generally recognised that cyclodextrins act as true carriers by keeping the hydrophobic drug

molecules in solution and delivering them to the surface of the biological membrane, e.g. skin,mucosa or the eye cornea, where they partition into the membrane. The relatively lipophilic
http://upload.wikimedia.org/wikipedia/commons/5/51/Cyclodextrin.svghttp://upload.wikimedia.org/wikipedia/commons/c/c6/Alpha-D-Glucopyranose.svghttp://upload.wikimedia.org/wikipedia/commons/5/51/Cyclodextrin.svghttp://upload.wikimedia.org/wikipedia/commons/c/c6/Alpha-D-Glucopyranose.svg


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membrane has a low affinity for the hydrophilic cyclodextrin molecules and therefore, they remain in

the aqueous membrane exterior, e.g. the aqueous vehicle system (such as o/w cream or hydrogel),

salvia or the tear fluid. Conventional penetration enhancers, such as alcohols and fatty acids, disrupt

the lipid layers of the biological barrier. Cyclodextrins, on the other hand, act as penetration

enhancers by increasing drug availability at the surface of the biological barrier. For example,

cyclodextrins have been used successfully in aqueous dermal formulations ,an aqueous mouthwash

solution ,nasal drug delivery systems and several eye drop solutions(Chloramphenicol). A large range

of cyclodextrins are already being used for several drug administrations:

-Cyclodextrin ->Alprostadil (vasodilatory properties and

erectile dysfunction treatment)

-Cyclodextrin ->Piroxicam (ulcer treatment)

2-Hydroxypropyl--cyclodextrin->Mitomycin compounds

(MitoExtra could be used for antitumor purposes agains

gastic, pancreatic and colorectal cancers)

Sugammadex (agent for reversal of neuromuscular blockade

caused by rocuronium or vecuronium)

Cyclodextrins and their uses: a reviewE.M. Martin Del Valle

Calixarenes

Calixarenes are cyclic oligomers, which are formed by benzene unitsbridged with methylene groups.

The components are derived from phenol, resorcinol or pyrogallol, by

hydroxyl alkylation with aldehydes. The chemical reaction ranks under

electrophilic aromatic substitutions followed by an elimination of water

and then a second aromatic substitution. The reaction is acid catalysed

or base catalysed. Calixarenes are difficult to produce because it is all

too easy to end up with complex mixtures of linear and cyclic oligomers with different numbers of

repeating units. With finely tuned starting materials and reaction conditions synthesis can also be

surprisingly easy. Afterwards, by de-t-butylation(in the presence of AlCl3, toluene and phenol) andsubstitution of the hidroxylic group, new modified calixarenes may be obtained.

Photodynamic therapy (PDT) is a novel treatment for cancer and certain noncancerous diseases that

are generally characterized by overgrowth of unwanted or abnormal cells; the therapy depends on

the retention of photosensitizers (Ps) in tumor cells, their activation within the tumor being achieved

through irradiation with light of appropriate wavelength. The destructive potential of PDT resides

mainly in the generation of reactive oxygen species produced by the light activated Ps (1). Through

the Shinkai methode, calix[6]arene-p-hexasulphonate and calix[8]arene-p-octasulphonate may be

obtained, yielding such photosensitive properties (of which, calix[6] is more favorable). Due to its

characteristics, calix[6] can be further developed as a more efficient drug delivery system inphotodynamic therapy approaches against the tested K562 tumor cells.

Sugammadex

Basic structure of

a Calixarene
http://upload.wikimedia.org/wikipedia/commons/c/c0/Sugammadex_sodium.svghttp://upload.wikimedia.org/wikipedia/commons/c/c0/Sugammadex_sodium.svghttp://upload.wikimedia.org/wikipedia/commons/c/c0/Sugammadex_sodium.svghttp://upload.wikimedia.org/wikipedia/commons/c/c0/Sugammadex_sodium.svghttp://upload.wikimedia.org/wikipedia/commons/c/c0/Sugammadex_sodium.svg


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Calixarenes are efficient sodium ionophores and are applied as such in chemical sensors. With the

right chemistry these molecules exhibit great selectivity towards other cations. Calixarenes are used

in commercial applications as sodium selective electrodes for the measurement of sodium levels in

blood.

ANTITUMORAL EFFECT OF CALIXARENES IN EXPERIMENTAL PHOTODYNAMIC THERAPY WITH K562TUMOR CELL LINE

MONICA NEAGU,* RODICA-MARIANA ION, GINA MANDA, CAROLINA CONSTANTIN, EUGEN RADU, ZOIA CRISTU

Cucurbituril

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cavitands - nanochemistry