Javier Montenegro Chemistry Research 1

The olfactory reception system allow us, the human beings, to distinguish around 10.000 different odours with only 350 olfactory receptors. Incompatibility with a 1 to 1 recognition this sensorial system requires the assistance of cross-responsive interactions to create spatial maps that are recognized as unique fingerprints in the brain.  We have applied these lesson from nature to construct differential sensors for the discrimination of many different analytes. For instance volatile hydrophobic molecules such as single atom carbon atoms (octanal, nonanal, decanal) cis/trans isomers or even enantiomers. Click here to read more about about it! We have recently developed a differential sensing system, operating in lipid bilayer membranes, for the challenging discrimination of complex polymers with biological relevance. We have been able to differentiate single, double stranded  and short nucleotides sequences with single nucleobase resolution. Click the graph to read the tale of the first DNA artificial nose!

Differential Sensing in lipid bilayers


A) Set of different cationic reactive counteirons Arg1Ox3, Arg2Ox3, Arg2Ox4. B) Formation of the oxime-amphiphiles Arg1(OxT10)3/DNA activated neutral complex that translocate the membrane. C) Fluorescence fingerprints of different anionic biopolymers allow discrimination trough pattern recognition.

Controlling and manipulating matter at the nanometric scale represents one of the mayor goals of nowadays science. Along these lines, the self-assembly of small monomers offers a great opportunity to generate nanometric structures with controlled topology. We know how to design and prepare peptide nanotubes and we can control the diameter and properties of these nanotubes by simply varying the sequence of the peptide used. We have recently used rationally designed hydrophilic cyclopeptides with a pyrene artificial amino acid to prepare hybrid tubular structures with carbon nanotubes.

Membrane Transport / Differential Sensing / Nanotechnology

Javier Montenegro Chemistry Research 2

Proposed model of coupling between SCPNs and SWCNTs, and representative TEM and AFM images. a) Structures of CP-1 and of a dimer. b) Plausible model of the coupling of CP-1 to CNTs, c) Plausible model of the attachment of SWCNT/SCPN hybrids to an anionic surface. d) TEM image of a SWCNT/SCPN hybrids after deposition from dispersion on a carbon holey grid. The white arrow indicates an SCPN-free segment of CNT, the black arrow a hybridized segment (scale bar 5 nm). e) AFM topographic image of dialyzed aqueous dispersions of SWCNT/SCPN hybrids deposited on mica, arrows as in (d). f) AFM height profile along the longitudinal axis of a nanotube (red line).

Javier Montenegro Chemistry Research 3

Dynamic Bonds for Membrane Transport

The lipid bilayer membrane is the dynamic barrier that Nature has selected to keep ions and biomolecules confined in the appropriate location. This cellular compartmentalization is of critical importance for all the processes that allow life in complex organisms. However, the membrane barrier represents a problem when trying to introduce probes and/or deliver therapeutics. Therefore it is imperative to find new conceptual ways to enter cells and cross the lipid bilayer. As organic chemists we design and synthesize new molecules that can cross cell membranes and help in the delivery of other molecules. We focus our efforts in the use of  dynamic covalent chemistry for the incorporation of the hydrophobic part of amphiphilic molecules that translocate the membrane and help in the delivery of polymers of biological interest. We use simple and facile synthetic methods to make molecules that we can evaluate in green fluorescent He-La cells for the delivery of interference RNA (siRNA).

Javier Montenegro Chemistry Research 4

Conceptual scheme for the formation of dynamic amphiphiles to transport polymers of biological interest and pictures demonstrating GFP knock-down in He-La cells. /2 hours post-transfections cell viability is easily recognized and the total lack of fluoresce reflects the correct delivery of siRNA.

Javier Montenegro Chemistry Research 5