Lecture 5 Bioelectronics Nature’s transistors, rectifiers, capacitors ………..

[O 2 ] Time ADP Slope  current Current through your mitochondria

The respiratory chain

Sugar O 2 + 4H + 2H 2 O Drop in E across gaps is conserved as proton gradient for ATP synthesis The mitochondrial battery E (mV)

Mitochondrial membrane electrons O 2 + 4e - + 4H +  2 H 2 O H+H+ Cytochrome c Oxidase An electron transfer-driven proton pump 5 metals ions 3 -redox centres Cu A (Bi-nuclear Cu) Haem a Haem a 3 - Cu b

HQNO Protein based conducting pathways Formate Dehydrogenase

Multielectron catalysts - molecular wires? Nitrite reductase NO H + + 8e -  NH H 2 O Hydroxylamine oxidase NH 2 OH  HNO 2 + 4H + + 4e -

Inspiration from Nature - molecular wires conducting in water 12nm

Marcus Theory For non-adiabatic electron transfer between donor and acceptor separated by distance R. D - |A + D|A k ET is a function of: Distance between D and A Driving force

Nature knows Marcus Theory Distance  ~ 1.4 Å -1 Driving force ~ 0.7 eV Page et al Nature (1998)

A physicist’s current is a biochemists rate Distance If  ~ 1.4 Å -1 then rate drops 10 fold every increase of 1.6Å between donor and acceptor s -1 = 1.6 µA 10 9 s -1 = 0.16 nA 10 3 s -1 = 0.16 fA

Protein based conducting pathways - mobile carriers Interprotein electron transfer - the cytochrome c/cytochrome b 5 paradigm _ _ + + Stopped-flow kinetics One of fastest known interprotein ET reactions Diffusion limited at low I Still 10 8 M -1 s -1 at physiological I Affinity measurements (by Spectrometry and potentiometry) Weak complex - K D 100µM at physiological I Potential measurements at bulk equilibrium and by direct electrochemistry at surfaces Cyt b 5 redox potential goes up mV when bound to a positively charged surface

Multihaem cytochromes - nature’s electrical contacts React with solid metal oxides Mobilisation of Fe II from solid iron oxides Reduction of soluble U VI to insoluble U IV oxides Shewanella - 39 multihaem cytochome genes

heterogeneous ET contact resistance Surface attachment/localisation 2D packing and interprotein ET - Source + Drain Bias application? Gating? A protein based transistor for nanotechnology?

A biochemically gated transistor? Analyte - +

Haem - a cofactor of choice l A conductor - cytochromes l A catalyst - P450’s l A carrier of dioxygen - globins l A sensor - for O 2, CO, NO, oxidation state - globins, CooA, PAS etc 1.5nm

How do we connect electronically to proteins? Protein electrochemistry Needs functionalised surfaces - e.g. SAMs on gold, ‘Special’ Graphite N S N S N S N S H3N+H3N+ S S COO - Thiopyridine Small peptides

Cytochrome c electrochemistry Electrochemically driven conformational change. N-state His-Fe-Met +270mV short timescale <100ms long timescale >1000s NRNR NONO AOAO ARAR i V OxRed A-state His-Fe-Lys -220mV

Electrochemistry and nanotechnology AFM on DNA aligned proteins Electrochemical AFM Electrochemical STM Test conductance of assemblies e.g. two tip STM or patterned electrodes and conducting AFM tips 500bp – 170nm