A model world for chemists

Modelling the details of a chemical reaction has always been a computational nightmare. Once the chemist considers interacting molecules with more than a handful of atoms, the complexity of the equations needed to describe the bonds that hold the atoms together and how they change during a reaction become far too much for even a supercomputer to portray accurately within a reasonable time.

Nobel-prize winning theories have over the years allowed chemists to develop simplifications that allow even proteins with their hundreds of atoms to be modelled to a high degree of accuracy in a matter of days rather than decades. But, even these simplifications don’t allow reactions to be modelled readily. Chemists would like to be able to simulate every atom and every bond and how they react with precision and rapidity. They may now have taken a step closer to this Holy Grail through ongoing work by Daniel Crawford and colleagues at Virginia Tech and Bethel College of St. Paul in Minnesota. There are many chemical reactions that you don’t want to do in the lab, explains Crawford, Perhaps they are too slow or too toxic or too explosive, or there may be micro- or nano-scopic components of reactions you can’t probe experimentally.

Daniel Crawford

Daniel Crawford

Quantum chemistry can unlock the secrets of reactions involving small molecules, such as ozone and a chlorofluorocarbon in atmospheric chemistry, say. But, consider the reaction of a steroidal hormone with an enzyme, or a pheromone with a vomeronasal receptor and the number of atoms involved is simply too high for even the most sophisticated of quantum chemistry computer programs to simulate.

The problem is that even simple-seeming molecules, such as the amino acids that comprise those protein receptors and enzymes, take days to compute. Consider two amino acids and the calculation time expands from days to years. Far too long for even the most patient PhD student!

Rollin King

Rollin King

Crawford and Bethel College’s Rollin King are now applying a technique called local correlation. The basic idea is to describe the electronic interactions in a molecule piece by piece. You shouldn’t have to consider interactions of electrons on parts of the molecule that are far apart, in general, so by breaking the molecule into fragments, we can reduce the cost (time) of the calculation, explains Crawford.

To take advantage of this local correlation approach, Crawford explains that he and his colleagues have had to completely reorganize their quantum chemistry computers programs. In some sense we have to start from scratch, he told Spotlight. We build the electronic wave functions using a set of localized orbitals rather than the usual so-called canonical orbitals, which are smeared across the entire molecular framework.

In this new, more focused set of orbitals, many pieces of the wave function (such as those corresponding to electronic interactions on distant atoms) become negligible. By reorganizing the programs to determine in advance which pieces are small, we can avoid computing and storing them from the beginning, he adds.

One of the most important target applications the team is shooting for is the simulation of optical activity in chiral, or handed, molecules. Many natural products and bioorganic compounds, including drugs, are chiral and in one handed form are safe and effective while in the other can be less effective or even dangerous.

Our goal is the development of a computational technique that will help organic chemists identify the absolute configuration – that is, the handedness — of a newly isolated chiral compound so that it can be synthesized in the laboratory, says Crawford. Such a development could potentially save months or even years of laboratory work. The problem, though, is that natural products are large, at least by quantum chemical standards, explains Crawford, To compute the optical activity, we have to be able to deal with systems containing 30-50 non-hydrogen atoms. This is where the local correlation idea comes in.

The researchers presented their results at the 223rd national meeting of the American Chemical Society, in Florida in April 2002.

Further reading

Daniel Crawford
http://www.chem.vt.edu/people/faculty/crawford-daniel/

Suggested searches

Quantum chemistry
Chemistry modelling
Wavefunctions
Molecular orbitals
Chirality

DNA and chips

The secret ingredient in a future biological computer is to add a little DNA. But, making hybrid devices from a silicon chip and a strand of genetic material means mixing hard-wired microelectronics technology with the softer world of molecular biology.

Now, chemists at the University of Newcastle upon Tyne have come up with a solution that could lead to new lab-on-a-chip devices and biological sensors for use in medicine and environmental analysis. It might even one day allow biology to compute or provide an interface between electronic devices and living things.

Ben Horrocks

Ben Horrocks

Newcastle chemists Benjamin Horrocks and Andrew Houlton and their colleagues have devised a way to automate the solid-phase synthesis of DNA on a semiconductor chip. They believe their method could readily be adapted to the conventional fabrication techniques of photolithography used in the microelectronics industry to pattern the microscopic transistors and circuitry on a computer chip.

The team recently reported how it has found a way to attach a DNA sequence of just seventeen nucleotides to a silicon surface modified with organic molecules. The key to unlocking hybrid DNA chips lies in the team’s use of bifunctional organic molecules. At one end the molecule has the right chemistry to allow it to be attached to an oxide-free silicon surface. The other end of the molecule has a functional chemical group on which a DNA strand can be grown using an automated DNA synthesizer of the kind found in biotech laboratories the world over.

Andrew Houlton

Andrew Houlton

The team is working with two aims in mind – first, the development of chemical sensors and secondly the synthesis of DNA on silicon surfaces for nanoscale molecular architecture. This addresses the projected reduction in the size of electronic components which by 2015 are predicted to be of the order of nanometres (i.e. built from molecules), explains Houlton.

Gel electrophoresis reveals DNA is attached to the silicon

Gel electrophoresis reveals DNA is attached to the silicon

Previous endeavours in this area have generally used glass in preference to silicon wafers and those that have focused on silicon have applied organic molecules to an oxidised surface rather than the naked silicon chip. The Newcastle team has now confirmed that it is possible to cover the surface of a silicon chip with DNA strands. Moreover, the 17-base DNA strands can be coupled with the complementary DNA strand making the familiar DNA double helix. From the nanodevice perspective the importance of the team’s work lies in their ability to pattern the surface of the silicon rather than simply randomly deposit DNA strands. Patterning using the printing and etching techniques of microelectronics fabrication means they can tightly control the arrangement of the DNA on the surface and so produce what might one day become molecular circuitry.

A DNA-patterned silicon surface

A DNA-patterned silicon surface

Sequential modification of a silicon surface with DNA

Sequential modification of a silicon surface with DNA

Further reading

Angew. Chem. Int. Ed., 41, 615 (2002)
http://www3.interscience.wiley.com/cgi-bin/abstract/90512278/ABSTRACT

DOI: 10.1002/1521-3773(20020215)41:4<615::AID-ANIE615>3.0.CO;2-Y

Benjamin Horrocks
http://www.ncl.ac.uk/chemistry/staff/profile/b.r.horrocks

Andrew Houlton
http://www.ncl.ac.uk/chemistry/staff/profile/andrew.houlton

Suggested searches

Molecular Electronics
Nanotechnology