Hartings Lab Bio Inorganic Chemistry
Project Outline
We are modifying hemoglobin, a common protein responsible for the red color in blood, so that is capable of converting carbon dioxide into more useful chemicals. Transforming hemoglobin will, initially, involve two basic steps. First, the heme molecule that gives hemoglobin many of its characteristics will be replaced with one of several similar molecules in order to make the reactivity of the modified-hemoglobin match up with the reactivity of CO2. Second, light-sensitive molecules will be attached to the surface of the protein. These molecules, upon absorbing light, will help to provide the energy that the CO2 reactions require.
(You can see what we’ve been doing by checking out our on-line notebooks.)
Inspiration
With photosynthesis, plants and algae are able to turn carbon dioxide and water into sugar (a chemical fuel) and oxygen. This reaction is not spontaneous; that is, it requires external energy in order to occur. The plants and algae get this energy from sunlight. These reactions are enabled with a large set of proteins called photosystem. Individual proteins in this system are responsible for absorbing light, converting water into oxygen, and pushing around electrons and protons so that the plants/algae can store energy and synthesize sugars and other more complex molecules using the simple CO2 building block.
The question our lab is asking is: Can we modify an individual protein so that it performs simpler versions of photosystem’s primary tasks. Specifically, can we make a single protein that can use absorbed light to drive the conversion of CO2 into carbon monoxide (CO) or formic acid (HCOOH)?
CO2 Conversion
Photosynthesis coupled with the Calvin cycle are responsible for creating many of the complex molecules plants and algae use for their everyday functions. What we are trying to do is much more modest, though not necessarily easily accomplished. Carbon dioxide can be converted into either CO and water or HCOOH through the addition of two protons (H+) and two electrons (e-) as shown in the CO2 reduction scheme below.
CO2 reduction reaction
While these molecules aren’t immediately as useful as glucose, CO and HCOOH are more reactive than CO2 and can be used as the starting point for synthesizing larger, more functional molecules.
Previous research has shown that several metal macrocycle complexes (shown in the figure below) are able to catalyze the CO2 reduction reaction (i.e. conversion into CO or HCOOH). These metal macrocycles operate in organic solvents in conjunction with either an electrode or a photosensitizer (both of which provide a source of electrons) to facilitate CO2 reduction.
Metal macrocycles that can catalyze the CO2 reduction reaction. In this figure M can correspond to any number of transition metals, specifically Mn, Fe, Co, Ni, and Cu.
Protein Scaffolds
The broad class of heme-containing proteins, which all perform different functions within a cell, have individually evolved to define very specific reactivities at the heme molecule (similar to an iron version of the porphyrin shown in the above figure). By inserting the heme or another macrocycle (containing one of any number of transition metals) into a protein, we believe that we can start to tailor the reactivity of these macrocycles to more efficiently carry out reactions of CO2. The protein on the left is one portion of the hemoglobin protein that is produced in Ascaris suum nematodes. This heme-containing protein has evolved, like other similar hemoglobins, for the purpose of carrying oxygen through the bloodstream.
We are working on modifying and designing new synthetic strategies for inserting macrocyclic molecules (similar to the ones shown above) that will be put inside of hemoglobin in place of (the standard) iron protoporphyrin IX (highlighted in the figure on the left).
Photo-induced Reactivity
The ultimate goal of this project is not only to enable CO2 reactivity within hemoglobin but to drive that reactivity using solar energy, mimicking photosynthesis. To that end, we need to be able to supply the CO2 reduction reaction with two electrons. In order to accomplish this, we will strategically place two photosensitizers on the surface of the protein. Photosensitizers (three examples of which are shown in the image below) are molecules that can donate electrons after they have absorbed ultraviolet/visible light.
Transition metal-based photosensitizers that will provide the electrons for CO2 reduction in our experiments.
Covalently attaching photosensitizers like these on the surface of the protein will provide a direct conduit between the electron source and the site of the CO2 reaction (i.e. the metal macrocycle.) The image on the left highlights (yellow) the most direct pathways between the sites where we are installing our photosensitizers (red spheres) and the metal macrocycle. Of note, and one of the reasons why this particular protein was chosen, are the placement of two aromatic residues (a tyrosine and a tryptophan) within the protein in proximity to both the macrocycle and the outer surface of the protein. It has been noted that aromatic amino acids can assist in speeding up an electron transfer process, and it is our hope that this will be the case for our experiments.
Questions
Our main question is: Can we create a protein that can mimic photosynthesis and use sunlight to turn carbon dioxide into other carbon-containing molecules. Achieving this and refining our system are long-term goals. Other questions we will be asking along the way are:
1) Can we develop methods to efficiently replace the heme in hemoglobin with non-aromatic macrocycles like cyclam?
2) How does the oxygen-binding capacity of hemoglobin change upon heme replacement with different macrocycles?
3) How does the electrochemistry of the macrocycles change upon insertion into hemoglobin?
4) What are the dynamics of simultaneous 2 electron transfer processes?
5) Multiple electron transfer reactions at electrodes show different potentials than the combined single electron transfer events. Is this also true for homogeneous systems?