Transport Processes and Carrier Design

• Organic Chemistry of– membrane transport processes – carrier molecules

• Carrier molecules -designed from receptor + organic and or inorganic substrates if membrane soluble - may induce selective transport -

membranes permeable to the bound species• Transport –represents one basic functional

feature of supramolecular species together with recognition and catalysis.

Chemsitry of Transport Systems Three Main Goals

1. Design Transport effectors

2. Devise transport processes

3. Investigate their applications in chemistry and biology.

Transport Processes

• Selective membrane permeability

induced either by

carrier molecules

or

transmembrane channels

– Fig 10

Carrier Mediated Transport(Facilitated Diffussion)

• Transfer of a substrate across a membrane, facilitated by a carrier molecule located in the membrane

Four Phases of Carrier Transport

• Cyclic Process –

1.Formation of the carrier-substrate complex at one interface

2.Diffusion of the complex through the membrane phase

3.Release of the substrate at the other interface

4.Back diffusion of the free carrier

• Process analogies with molecular catalysis• Physical catalysis – change in location• Translocation on the substrate (chemical

catalysis-transformation into products)• Transport catalyst – carrier – inc. rate of

passage of substrate with respect to free diffusion and shows enzyme-like features

• Active species – carrier-substrate supermolecule• Transport of substrate S1 may be coupled to

flow of second molecule S2 in the same (symport) or opposite (antiport) direction

Organic Chemistry of Membrane Transport

• Carrier design major feature– Carrier determines

– Nature of substrate– Rate selectivity– Type of process – facilitated diffusion

active transportcoupling to gradients

and flows of other species

• Synthetic Carrier – (can be modified at will)– Monitor transport process via the structure of the

ligand– Analyze the effect of various structural units on the

thermodynamic and kinetic parameters that determine transport rates and selectivity

Factors influencing Selective Transport

• Internal– Ones arising from the carrier

• External– Ones arising from the medium

• Diffusion Controlled Process – Rates depend on the thermodynamic

equilibria at the interfaces– i.e. relative extraction efficiency towards different

substrates

Carrier Design

• Take into account factors specific for transport processes.

• Carrier Molecule– Highly Selective– Not bind substrate too tightly– Be flexible enough to allow sufficiently fast exchange rates for

loading and unloading– Avoid carrier saturation– Suitable lipophilic-hydrophilic balance – so can be soluble in

membrane phase while same time being able to reach interface and enter into contact with the aqueous phase

– Not too bulky – diffuse rapidly– Have functional groups – suitable for coupling of substrate flow

with other processes (acid/base, redox)

External Factors

• Comprise the nature of the membrane• Substrate concentration in aq. Phase and any

other external factor that may participate in the process

• Strongly influence transport rate via the phase distribution equilibria and ddiffusion rates– Ex. Neutral ligand carry ion pair by complexing either

cation or anion –the coextracted uncomplexed counterion will affect the rate by modifying the phase distribution of the substrate

– Cationic Complex and a counterion – Fig. 10

Cation Transport Processes – Cation Carriers

• Inorganic Cations-– Ex. Alkali transport initial objectives with work on

cryptates• Selective ion carriers - natural acyclic and

macrocyclic ligands– Monensin– Valinomycin– Enniatin– Nonactic

• Ionophores• Lipophilize cations by complexation and to

extract them into an organic or membrane phase

• Cryptands (7-9) and derivatives carry alkali cations

• Cryptands – optimal complex stability and phase-transfer equilibrium for highest transport rates

• The rates of transport by proton ionizable macrocyclic carriers are pH dependent

• Other ligands used as carriers – acyclic polyethers or claixarene derivatives

Applications

• Control levels of biologically active

• Selective transport of transition metal ions

• Removal of toxic heavy metal ions from biological fluids or from the environment

• Recovery of trace metals

• Separation procedures

• Macrocyclic Polyethers– Selectively transport organic primary

ammonium cations– Chiral carriers effect the resolution of racemic

ammonium salts

• Crown ethers– Facilitate the transport of guanidinium cations

External factors on transport rates

• Nature of membrane phase– Influences distribution equilbria and – Stability and selectivity of the complex in the

membrane and the cation exchange rates at the interfaces

– Nature of the coextracted anion affects transport via a (cationic complex-anion) pair –Fig 10 simply by modifying the amount of salt extracted into the membrane; this amount decreases with highter hydration energy and lower lipophilicity of the anion.(e.g. chloride vs. picrate)

– The concentration of salt in the aqueous phase will affect the amount extracted into the membrane and therefore the transport rates.

Anion Transport Processes – Anion Carriers

• Lipophilic cations – (ammonium ions bearing long hydrocarbon chains) – allow anion extraction into an organic phase and render liquid membranes permeable to anions by anion exchange (antiport) process

• Such carriers effect – selective transport of amino acid carboxylates against inorganic anions like chloride

• Solubilization and transport of ion pairs by cation complexing agents (above) involves transport of the anion as external component of the complexed cation-anion pair

• Lipophilic transition metal complexes or organometalic derivatives may serve as anion carriers by direct coordination of the anion to the metal cation and should provide a variety of selectivity features

• Anion binding to lipophilic porphyrin complexes

• Inorganic anions carried by protonated cryptands and oligopyrrole macrocycles

• Transport of carboxylates and phosphates –of interest b/c biological significance

• The transport of nucleotides has been achieved• Transport of ATP significant with respect to bioenergetic

processes.• Anitviral chemotherapy –take advantage of enhancing

the cellular uptake of modified nucleotides by carrier species

• Carriers for polynucleotides and nucleic acid segments and thus capable of mediating gene transfer – value for biotechnology, genetic engineering and gene therapy

• Recombinant viruses –efficient genes transfer agents

• Synthetic vectors • Mixed - adenovirus-polylysine-DNA conjugates• Lipopolyamines –purely synthetic• Are also able to induce marked transfection and

represent very promising alternatives that would alleviate problems linked with using viral material

• Great basic and applied interest in biology and medicine for further development of artificial vectors capbable of inducing efficient and stable gene-transfer

• Lipophilic guanidinium species – may be envisaged in view fo the strong interactions between nucleic acids and the polyarginine peptides, protamines.

• Liposomes act as agents for DNA transfer

Liquid Membranes

• Allow extraction of toxic species from biological fluids and regeneration of dialysates or ultrafiltrates, as required for artificial kidneys

• Substrates would diffuse through the liquid membrane and be trapped in the dispersed aqueous phase of the emulsion

Cation-anion cotransport

Neutral molecules