A switching cascade of hydrazone-based rotary switches through coordination-coupled proton relays

Imidazole, a subunit of histidine, plays a crucial role in proton-relay processes that are important for various biological activities, such as metal efflux, viral replication and photosynthesis. We show here how an imidazolyl ring incorporated into a rotary switch based on a hydrazone enables a switching cascade that involves proton relay between two different switches. The switching process starts with a single input, zinc(II), that initiates an E/Z isomerization in the hydrazone system through a coordination-coupled proton transfer. The resulting imidazolium ring is unusually acidic and, through proton relay, activates the E/Z isomerization of a non-coordinating pyridine-containing hydrazone switch. We hypothesize that the reduction in the acid dissociation constant of the imidazolium ring results from a combination of electrostatic and conformational effects, the study of which might help elucidate the proton-coupled electron-transfer mechanism in photosynthetic bacteria. Metal cations play an important role in biological proton relays by modulating the pKa values of surrounding amino acids. This effect has now been used to induce the isomerization of two hydrazone switches using a single input. It is found that a combination of electrostatic repulsion and conformational changes are required for the proton relay to take place.

[1]  H J Morowitz,et al.  Molecular mechanisms for proton transport in membranes. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[2]  I. Aprahamian,et al.  Switching through coordination-coupled proton transfer. , 2011, Angewandte Chemie.

[3]  David A Leigh,et al.  A synthetic small molecule that can walk down a track. , 2010, Nature chemistry.

[4]  R. Lamb,et al.  A functionally defined model for the M2 proton channel of influenza A virus suggests a mechanism for its ion selectivity. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[5]  J. Platts,et al.  The effect of intramolecular interactions on hydrogen bond acidity. , 2003, Organic & biomolecular chemistry.

[6]  W. R. Wadt,et al.  Ab initio effective core potentials for molecular calculations , 1984 .

[7]  R. J. Williams,et al.  Proton circuits in biological energy interconversions. , 1988, Annual review of biophysics and biophysical chemistry.

[8]  G. Feher,et al.  Identification of the proton pathway in bacterial reaction centers: inhibition of proton transfer by binding of Zn2+ or Cd2+. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[9]  G. Whitesides,et al.  Complexity in chemistry. , 1999, Science.

[10]  G. Pavlović,et al.  The synthesis and structural study of two benzothiazolyl azo dyes: X-ray crystallographic and computational study of azo–hydrazone tautomerism , 2009 .

[11]  Yinan Wei,et al.  Binding and Transport of Metal Ions at the Dimer Interface of the Escherichia coli Metal Transporter YiiP* , 2006, Journal of Biological Chemistry.

[12]  M. Barboiu.  Imidazole I–quartet Water and Proton Dipolar Channels , 2012 .

[13]  Taiho Kambe,et al.  Identification of the Zn2+ Binding Site and Mode of Operation of a Mammalian Zn2+ Transporter* , 2009, The Journal of Biological Chemistry.

[14]  M. Thurnauer,et al.  EPR investigation of Cu2+-substituted photosynthetic bacterial reaction centers: evidence for histidine ligation at the surface metal site. , 2000, Biochemistry.

[15]  P. Maróti,et al.  Retardation of proton transfer caused by binding of the transition metal ion to the bacterial reaction center is due to pKa shifts of key protonatable residues. , 2001, Biochemistry.

[16]  Francesco Zerbetto,et al.  Synthetic molecular motors and mechanical machines. , 2007, Angewandte Chemie.

[17]  R. Astumian,et al.  Imposed oscillations of kinetic barriers can cause an enzyme to drive a chemical reaction away from equilibrium , 1993 .

[18]  Cam Patterson,et al.  Welcome to the machine: a cardiologist's introduction to protein folding and degradation. , 2002, Circulation.

[19]  D. Fu,et al.  Selective Metal Binding to a Membrane-embedded Aspartate in the Escherichia coli Metal Transporter YiiP (FieF)* , 2005, Journal of Biological Chemistry.

[20]  R. Lamb,et al.  Influenza A Virus M2 Ion Channel Activity Is Essential for Efficient Replication in Tissue Culture , 2002, Journal of Virology.

[21]  Daniel L DuBois,et al.  Development of molecular electrocatalysts for CO2 reduction and H2 production/oxidation. , 2009, Accounts of chemical research.

[22]  Parr,et al.  Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. , 1988, Physical review. B, Condensed matter.

[23]  R. Breslow.  Biomimetic Chemistry: Biology as an Inspiration , 2009, Journal of Biological Chemistry.

[24]  A. Becke.  Density-functional thermochemistry. , 1996 .

[25]  R. Hayward,et al.  Enhancement of anhydrous proton transport by supramolecular nanochannels in comb polymers. , 2010, Nature chemistry.

[26]  P. A. Christiansen,et al.  IMPROVED Ab Initio EFFECTIVE CORE POTENTIALS FOR MOLECULAR CALCULATIONS , 1979 .

[27]  E. F. Godefroi,et al.  2-(2-Imidazolyl)acetophenones. Preparation and some reactions , 1975 .

[28]  A. Taly,et al.  Effect of binding of Cd2+ on bacterial reaction center mutants: proton-transfer uses interdependent pathways. , 2002, Biochemistry.

[29]  Mei Hong,et al.  Mechanisms of Proton Conduction and Gating in Influenza M2 Proton Channels from Solid-State NMR , 2010, Science.

[30]  W. Goddard,et al.  Isomerization mechanism in hydrazone-based rotary switches: lateral shift, rotation, or tautomerization? , 2011, Journal of the American Chemical Society.

[31]  H. Gray,et al.  Proton-coupled electron flow in protein redox machines. , 2010, Chemical reviews.

[32]  G. Feher,et al.  Mechanism of proton transfer inhibition by Cd(2+) binding to bacterial reaction centers: determination of the pK(A) of functionally important histidine residues. , 2003, Biochemistry.

[33]  J. F. Stoddart,et al.  Great expectations: can artificial molecular machines deliver on their promise? , 2012, Chemical Society reviews.

[34]  J. F. Stoddart,et al.  The Chemistry of the Mechanical Bond , 2009 .

[35]  Ben L Feringa,et al.  Dynamic Control of Chiral Space in a Catalytic Asymmetric Reaction Using a Molecular Motor , 2011, Science.

[36]  Ville R. I. Kaila,et al.  Proton-coupled electron transfer in cytochrome oxidase. , 2010, Chemical reviews.

[37]  A. Credi,et al.  Molecular Devices and Machines: Concepts and Perspectives for the Nanoworld , 2008 .

[38]  G. Feher,et al.  Structure and function of bacterial photosynthetic reaction centres , 1989, Nature.

[39]  M. Thurnauer,et al.  Metal ion modulated electron transfer in photosynthetic proteins. , 2004, Accounts of chemical research.

[40]  A. Becke.  Density-functional thermochemistry. III. The role of exact exchange , 1993 .

[41]  Ram Devanathan,et al.  Recent developments in proton exchange membranes for fuel cells , 2008 .

[42]  I. Aprahamian,et al.  Switching around two axles: controlling the configuration and conformation of a hydrazone-based switch. , 2011, Organic letters.

[43]  I. Aprahamian,et al.  A pH activated configurational rotary switch: controlling the E/Z isomerization in hydrazones. , 2009, Journal of the American Chemical Society.

[44]  Induced conformational changes upon Cd2+ binding at photosynthetic reaction centers. , 2005, Proceedings of the National Academy of Sciences of the United States of America.