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 transport
coupling 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