Biobased Nanostructural Materials: New Opportunities for the Forest Products Industry

1. Biobased Nanostructural Materials: New Opportunities for the Forest Products Industry? Joseph J. Bozell Forest Products Center � Biomass Chemistry LaboratoriesUniversity of Tennessee Knoxville, TN 37996 jbozell@utk.edu Good afternoon�I�m Joe Bozell, and I�d like to welcome everyone to this session of the TAPPI meeting on Nanotechnology, and our session on Implications of Nanotechnology in Biorefinery Processes and Products. This is a very broad title, since the possibilities for nanoscale materials within the Forest Biorefinery are large and diverse. What Tim and I have tried to do is choose a few select areas where nanotechnology could be important, and invite speakers to discuss these areas. I need to announce that we had a last minute cancellation. Due to health issues, our last speaker in today�s session, Nicholas Kotov, was unable to make it today. Thus, we will have two presentations today and three in tomorrow morning�s session.Good afternoon�I�m Joe Bozell, and I�d like to welcome everyone to this session of the TAPPI meeting on Nanotechnology, and our session on Implications of Nanotechnology in Biorefinery Processes and Products. This is a very broad title, since the possibilities for nanoscale materials within the Forest Biorefinery are large and diverse. What Tim and I have tried to do is choose a few select areas where nanotechnology could be important, and invite speakers to discuss these areas. I need to announce that we had a last minute cancellation. Due to health issues, our last speaker in today�s session, Nicholas Kotov, was unable to make it today. Thus, we will have two presentations today and three in tomorrow morning�s session.

2. Presentation Topics Renewables and the biorefinery A few examples of carbohydrate nanotechnology opportunities Self assembling carbohydrate based bolaforms and their interaction with cellulose Tim asked me to speak today on the forest biorefinery context and some of the opportunities that might exist there for new nanoscale materials and products. So what I�ll talk about today is an overview of the biorefinery and how we view it, give a few examples from the literature about some nanoscale materials arising from process streams that would be available within the forest biorefinery, and then describe some of the work we have going on in our lab to make new nanoscale materials from carbohydrates.Tim asked me to speak today on the forest biorefinery context and some of the opportunities that might exist there for new nanoscale materials and products. So what I�ll talk about today is an overview of the biorefinery and how we view it, give a few examples from the literature about some nanoscale materials arising from process streams that would be available within the forest biorefinery, and then describe some of the work we have going on in our lab to make new nanoscale materials from carbohydrates.

3. The Biorefinery as a Unifying Concept We use the biorefinery as a unifying concept for the work that goes on at the Forest Products Center, and it�s well known to this audience that the biorefinery is developing as exactly analogous to the petrochemical refinery. That is�We use the biorefinery as a unifying concept for the work that goes on at the Forest Products Center, and it�s well known to this audience that the biorefinery is developing as exactly analogous to the petrochemical refinery. That is�

4. Forest Products Matrix And the forest biorefinery is simply a specialized example of the broader biorefinery concept. Now it�s safe to say that the FPI has been doing some biorefining for years, but what is happening more recently is an evolution of the processes normally associated with using the forest resource. That is, we have conventional processes�DESCRIBE But we also have more recent activities to develop more sophisticated refining processes�DESCRIBE The important feature of this evolution is that the forest products industry has the potential of realizing an Increasing value for their process streams as one goes down the list. Potential for increasing opportunity, flexibility and profitability of the forest resource as one goes down the list. Increasing distance between sm and product as one goes down the list.And the forest biorefinery is simply a specialized example of the broader biorefinery concept. Now it�s safe to say that the FPI has been doing some biorefining for years, but what is happening more recently is an evolution of the processes normally associated with using the forest resource. That is, we have conventional processes�DESCRIBE But we also have more recent activities to develop more sophisticated refining processes�DESCRIBE The important feature of this evolution is that the forest products industry has the potential of realizing an Increasing value for their process streams as one goes down the list. Potential for increasing opportunity, flexibility and profitability of the forest resource as one goes down the list. Increasing distance between sm and product as one goes down the list.

5. Strategic Goals for the Use of Renewable Feedstocks and Biorefinery Development Dramatically reduce, or even end, dependence on foreign oil (a displacement and energy component) Spur the creation of a domestic bioindustry (an enabling and economic component) And our interest in this evolution is particularly focused on the development of new chemical products for the biorefinery�there�s some good rationale for carrying out this approach. If one examines the use of renewable feedstocks at a very high level, two primary drivers can be identified. First, a key goal would be to find a way to move away from dependence on non-domestic sources of raw materials. This is a frequently repeated goal, and is one of displacement, focusing on making an energy impact. For the most part, this strategic goal will be addressed by production of high volume, low value biofuels. But at the same time, a financial incentive must exist to build facilities able to use renewables as feedstocks, and make industry willing to try new raw materials and technology for their conversion. This is the driver to enable a new industry, and has a very strong economic component. For the most part, this goal will be met through the production of higher value, lower volume chemical products. In fact, production of chemicals is very much the enabling component behind the anticipated success of the biorefinery. We continue to find that integrating chemical and fuel production is the most effective way to address both goals. E. g., one can build EtOH-only production facilities, but the return on investment is quite low, possibly slowing industrial development. Conversely, one can build a chemical-only operation, but since chemical products only make up 6-8% of the consumption of nonrenewables, the energy impact will be low. Together, one can realize both an energy and economic impact that will drive development of the industry. But if the integration of chemical and fuel production is indeed the lynchpin to successful biorefinery development, how do we start to get a handle on what the impact of chemical production might be, and how it interacts with fuel production? And our interest in this evolution is particularly focused on the development of new chemical products for the biorefinery�there�s some good rationale for carrying out this approach. If one examines the use of renewable feedstocks at a very high level, two primary drivers can be identified. First, a key goal would be to find a way to move away from dependence on non-domestic sources of raw materials. This is a frequently repeated goal, and is one of displacement, focusing on making an energy impact. For the most part, this strategic goal will be addressed by production of high volume, low value biofuels. But at the same time, a financial incentive must exist to build facilities able to use renewables as feedstocks, and make industry willing to try new raw materials and technology for their conversion. This is the driver to enable a new industry, and has a very strong economic component. For the most part, this goal will be met through the production of higher value, lower volume chemical products. In fact, production of chemicals is very much the enabling component behind the anticipated success of the biorefinery. We continue to find that integrating chemical and fuel production is the most effective way to address both goals. E. g., one can build EtOH-only production facilities, but the return on investment is quite low, possibly slowing industrial development. Conversely, one can build a chemical-only operation, but since chemical products only make up 6-8% of the consumption of nonrenewables, the energy impact will be low. Together, one can realize both an energy and economic impact that will drive development of the industry. But if the integration of chemical and fuel production is indeed the lynchpin to successful biorefinery development, how do we start to get a handle on what the impact of chemical production might be, and how it interacts with fuel production?

6. Impacts of Product Integration with Fuels One example of the potential impact of fuel/chemical integration in biorefinery development. And external evaluations further validate this trend. DuPont has recently started production of 1,3-propanediol at the Loudon, TN facility, using corn as the feedstock. They are co-located with an EtOH facility. But the driver for this operation is economic. DuPont evaluated the return on investment for three scenarios. The first looked at PDO production from fossil fuel in a conventional chemical operation, and found an ROI of about 11%. In scenario 2, separate EtOH and PDO production operations were evaluated, and the economics resulted in a projected 3% ROI, making that scenario a nonstarter. Finally, integration of PDO production with EtOH production was evaluated�and showed a significant ROI of 20%. In addition, the use of bioproduction for PDO instead of traditional chemical technology, they also realized significant energy advantages. Total energy use dropped 72%, petroleum use dropped 90%, and natural gas dropped 54%. Again, goals 1 and 2 were realized by integration of chemical and fuel production.One example of the potential impact of fuel/chemical integration in biorefinery development. And external evaluations further validate this trend. DuPont has recently started production of 1,3-propanediol at the Loudon, TN facility, using corn as the feedstock. They are co-located with an EtOH facility. But the driver for this operation is economic. DuPont evaluated the return on investment for three scenarios. The first looked at PDO production from fossil fuel in a conventional chemical operation, and found an ROI of about 11%. In scenario 2, separate EtOH and PDO production operations were evaluated, and the economics resulted in a projected 3% ROI, making that scenario a nonstarter. Finally, integration of PDO production with EtOH production was evaluated�and showed a significant ROI of 20%. In addition, the use of bioproduction for PDO instead of traditional chemical technology, they also realized significant energy advantages. Total energy use dropped 72%, petroleum use dropped 90%, and natural gas dropped 54%. Again, goals 1 and 2 were realized by integration of chemical and fuel production.

7. What Product Should We Make? The DOE �Top 12� products from sugars: Biomass as a feedstock for products is an issue of current high interest to a wide range of industrial segments. Develop technology to make inexpensive building blocks of defined carbon number and businesses will develop. Lignin product development is important. Now�these evaluations are helpful starting points, and suggest that products need to be a part of any biorefinery development activities�but the fact remains that the biorefinery industry must learn how to use structures that are significantly different than those used by the petrochemical industry. As a result, product development frequently boils down to the question of �what product should we make?� Unfortunately, the question of preidentifying structures prior to initiating research can be nonproductive if one doesn�t yet understand the types of reactions the raw material and associated building blocks will undergo. Some starts have been made to address this issue, for example, the DOE top 10/12 report. This report pre-identified a small group of structures that could reasonably be made from biomass. However, the intent of the report was not to define structures�rather, these compounds were closely linked to broader technologies that needed to be developed using these structures as a backdrop. These technologies could be applied to the synthesis of several of the top 10, or even better, structures that the industry might define, but aren�t on the list. The upshot of the report was technology development, both fundamental and applied, will have the greatest impact, and that the biorefinery of 2050 may or may not be making itaconic acid, but it will certainly be using the broad technologies that were developed for its synthesis. The industrial response to this report has validated this approach, and pointed out that programs to develop technology first were of greatest importance, as long as they led to construction of discrete chemical intermediates at low cost. There was a very interesting sense of �if you build it, they will come� from the industries that we spoke with.Now�these evaluations are helpful starting points, and suggest that products need to be a part of any biorefinery development activities�but the fact remains that the biorefinery industry must learn how to use structures that are significantly different than those used by the petrochemical industry. As a result, product development frequently boils down to the question of �what product should we make?� Unfortunately, the question of preidentifying structures prior to initiating research can be nonproductive if one doesn�t yet understand the types of reactions the raw material and associated building blocks will undergo. Some starts have been made to address this issue, for example, the DOE top 10/12 report. This report pre-identified a small group of structures that could reasonably be made from biomass. However, the intent of the report was not to define structures�rather, these compounds were closely linked to broader technologies that needed to be developed using these structures as a backdrop. These technologies could be applied to the synthesis of several of the top 10, or even better, structures that the industry might define, but aren�t on the list. The upshot of the report was technology development, both fundamental and applied, will have the greatest impact, and that the biorefinery of 2050 may or may not be making itaconic acid, but it will certainly be using the broad technologies that were developed for its synthesis. The industrial response to this report has validated this approach, and pointed out that programs to develop technology first were of greatest importance, as long as they led to construction of discrete chemical intermediates at low cost. There was a very interesting sense of �if you build it, they will come� from the industries that we spoke with.

8. Potential Market Impact of Nanotechnology NSF: $1 trillion by 2015 BCC research (www.bccresearch.com): $9.4 billion (2005) $10.5 billion (2006) $25.2 billion (2011) UK estimate: $1.275 trillion by 2010 (www.uktradeinvest.gov.uk) Draper Fisher Jarvetson: $600 billion by 2012 Thus, in that context, we are looking at how biorefinery process streams might be converted into new nanostructural materials. It�s a broad area, with many fundamental and applied R&D opportunities, and also one that has been associated with potentially large financial rewards, as shown here. You can see that the estimates for nano are really all over the map, from a high of almost $3 trillion (!!) by 2015, to the �benchmark� value of $1 trillion set by NSF a few years back. However, I think the message here is that many analysts believe that the market will be �large� even if the exact dollar values are still unknown. The related message is that converting the renewable process streams into nanostructural materials would be a good, general target to pursue as one tries to define a product slate that might arise from the forest biorefinery.Thus, in that context, we are looking at how biorefinery process streams might be converted into new nanostructural materials. It�s a broad area, with many fundamental and applied R&D opportunities, and also one that has been associated with potentially large financial rewards, as shown here. You can see that the estimates for nano are really all over the map, from a high of almost $3 trillion (!!) by 2015, to the �benchmark� value of $1 trillion set by NSF a few years back. However, I think the message here is that many analysts believe that the market will be �large� even if the exact dollar values are still unknown. The related message is that converting the renewable process streams into nanostructural materials would be a good, general target to pursue as one tries to define a product slate that might arise from the forest biorefinery.

9. What Will The Forest Products Biorefinery Look Like? Now�this approach is meant to be complementary to that proposed in the 2005 report on nanotech for the forest products industry. This slide provides a cartoon of what the forest biorefinery might look like. Woody biomass will be separated into its lignin and sugar components (at the simplest level), and will continue to be converted into pulp and paper products. A large portion of the nanotech report focused on how nanotechnology might be used to improve this process through addition of nanoscale materials, understanding of plant cell wall processes at the nanoscale, looking at how these materials self assemble, etc.Now�this approach is meant to be complementary to that proposed in the 2005 report on nanotech for the forest products industry. This slide provides a cartoon of what the forest biorefinery might look like. Woody biomass will be separated into its lignin and sugar components (at the simplest level), and will continue to be converted into pulp and paper products. A large portion of the nanotech report focused on how nanotechnology might be used to improve this process through addition of nanoscale materials, understanding of plant cell wall processes at the nanoscale, looking at how these materials self assemble, etc.

10. What Will The Forest Products Biorefinery Look Like? But in our case, we�re looking at the other potential outputs of the Forest Biorefinery, and seeing how the integration of chemicals and fuels could provide some of the economic advantages projected by the chemical industry. That is, the combination of traditional PnP products with a chemical and fuel stream would very likely provide a potentially high return on investment for an integrated forest products biorefinery. And in our case, we�re not looking at nanotechnology to improve existing process streams, we are looking to use these existing process streams to provide a source of starting materials for conversion in to new nanoscale materials.But in our case, we�re looking at the other potential outputs of the Forest Biorefinery, and seeing how the integration of chemicals and fuels could provide some of the economic advantages projected by the chemical industry. That is, the combination of traditional PnP products with a chemical and fuel stream would very likely provide a potentially high return on investment for an integrated forest products biorefinery. And in our case, we�re not looking at nanotechnology to improve existing process streams, we are looking to use these existing process streams to provide a source of starting materials for conversion in to new nanoscale materials.

11. Natural Polymers as Templates For example, the literature reports quite a large amount of work in using cellulose fibers as templates for new highly ordered nanoceramics and nanocomposites. This slide shows the general approach, in that a highly ordered polymeric material, such as cellulose, can be coated with a wide range of materials, with a wide range of processes. After coating of the cellulose with these materials, the cellulose can be removed by sintering or heating to give new metal carbides or oxides such as alumina, ziroconia, titania.For example, the literature reports quite a large amount of work in using cellulose fibers as templates for new highly ordered nanoceramics and nanocomposites. This slide shows the general approach, in that a highly ordered polymeric material, such as cellulose, can be coated with a wide range of materials, with a wide range of processes. After coating of the cellulose with these materials, the cellulose can be removed by sintering or heating to give new metal carbides or oxides such as alumina, ziroconia, titania.

12. �Artificial Fossils� from Cellulose Templates And this templating allows the order in cellulose to be transferred to the coating materials. Ti interspersed with Au particles gives new photocatalysts, SnO2 results in new gas sensing devices, nanoelectrodes can be made from Ag while zirconia leads to new catalytically active surfaces. Indium tin oxide templated on cellulose can be converted to new electronic materials. And in each case, using cellulose as a template leads to materials showing improved properties over similar non-templated materials.And this templating allows the order in cellulose to be transferred to the coating materials. Ti interspersed with Au particles gives new photocatalysts, SnO2 results in new gas sensing devices, nanoelectrodes can be made from Ag while zirconia leads to new catalytically active surfaces. Indium tin oxide templated on cellulose can be converted to new electronic materials. And in each case, using cellulose as a template leads to materials showing improved properties over similar non-templated materials.

13. Cellulose/CaCO3 Nanocomposites as Artificial Bone Organized polymers can template CaCO3 Bacterial cellulose forms a fine, highly organized template Acid functionalization promotes biomineralization Cellulose needn�t be removed after its use as a template. There is considerable work underway to use cellulose as a template for inducing biomineralization of CaCO3, and the construction of artificial bone for grafting or replacement of missing tissue. Cellulose, and in particular, bacterial cellulose, can provide a well organized substrate for CaCO3 crystallization as shown in the pictures. The cellulose can be functionalized with acid groups to improve mineralization, as COOH groups are known to promote this effect. And there are many places in the human body where bone substitutes have been found useful.Cellulose needn�t be removed after its use as a template. There is considerable work underway to use cellulose as a template for inducing biomineralization of CaCO3, and the construction of artificial bone for grafting or replacement of missing tissue. Cellulose, and in particular, bacterial cellulose, can provide a well organized substrate for CaCO3 crystallization as shown in the pictures. The cellulose can be functionalized with acid groups to improve mineralization, as COOH groups are known to promote this effect. And there are many places in the human body where bone substitutes have been found useful.

14. Biological and Polymer Applications Medical diagnostics, biochips, biosensors Nanomolar sensitivity for detection of biotin-containing species Cellulose provides a new set of support properties PVA/cellulose composites Magnetic alignment of cellulose nanofibers Improved mechanical properties Functionalized cellulose has been used for the production of new biosensors. For example, cellulose is coated with TiO2, and the TiO2 is then functionalized with biotin. The biotin can link to proteins which can link to other biomaterials in solution. This arrangement has been used to develop highly sensitive biosensors, potentially useful for the detection of toxic organisms or other biologically active materials. Cellulose nanofibers also have the interesting property of aligning in a magnetic field�this property has been used to form PVA films containing alignned cellulose fibers. The resulting material exhibits improved strength.Functionalized cellulose has been used for the production of new biosensors. For example, cellulose is coated with TiO2, and the TiO2 is then functionalized with biotin. The biotin can link to proteins which can link to other biomaterials in solution. This arrangement has been used to develop highly sensitive biosensors, potentially useful for the detection of toxic organisms or other biologically active materials. Cellulose nanofibers also have the interesting property of aligning in a magnetic field�this property has been used to form PVA films containing alignned cellulose fibers. The resulting material exhibits improved strength.

15. Bolaforms As Self Assembling Systems We can also move from the use of cellulose as a polymeric material in the biorefinery to its use as a source of monomeric sugars. This approach is certainly of importance in the production of biofuels, such as EtOH, but also as a source of new chemical building blocks from the forest resource. One of the areas we are currently looking at is the use of sugars as components of new nanostructural materials. The specific project I�d like to discuss tonight is the work that we are doing in using biobased building blocks as components of new nanostructural materials. Our interest in this area is linked to the biorefinery in that we believe that we have developed some interesting biobased materials that may lead to new, nanoscale products. As this audience is well aware, nanotechnology has achieved real �buzzword� status, but nonetheless, projections of a trillion dollar industry over the next decade or so have been projected. Our focus is on the use of carbohydrates to make new examples of the so called �bolaforms� or �bolaamphiphiles�. The general structure of these materials is shown at the top, and refers to a compound possessing two polar headgroups linked by a long, nonpolar chain. The origin of the term is from the Spanish bola, referring to the weighted lariat used on South American cattle operations. A wide number of these materials have been reported in the literature as shown. One of the characteristics of these materials is their ability to undergo assembly into monolayer membranes. The particularly large, very complex but elegant structure is found in extremeophilic arachaebacteria, can separate extreme physiological differences: inside a membrane composed of these bolaforms, pH of 6.5, but outside can be as low as 1.5.We can also move from the use of cellulose as a polymeric material in the biorefinery to its use as a source of monomeric sugars. This approach is certainly of importance in the production of biofuels, such as EtOH, but also as a source of new chemical building blocks from the forest resource. One of the areas we are currently looking at is the use of sugars as components of new nanostructural materials. The specific project I�d like to discuss tonight is the work that we are doing in using biobased building blocks as components of new nanostructural materials. Our interest in this area is linked to the biorefinery in that we believe that we have developed some interesting biobased materials that may lead to new, nanoscale products. As this audience is well aware, nanotechnology has achieved real �buzzword� status, but nonetheless, projections of a trillion dollar industry over the next decade or so have been projected. Our focus is on the use of carbohydrates to make new examples of the so called �bolaforms� or �bolaamphiphiles�. The general structure of these materials is shown at the top, and refers to a compound possessing two polar headgroups linked by a long, nonpolar chain. The origin of the term is from the Spanish bola, referring to the weighted lariat used on South American cattle operations. A wide number of these materials have been reported in the literature as shown. One of the characteristics of these materials is their ability to undergo assembly into monolayer membranes. The particularly large, very complex but elegant structure is found in extremeophilic arachaebacteria, can separate extreme physiological differences: inside a membrane composed of these bolaforms, pH of 6.5, but outside can be as low as 1.5.

16. Carbohydrate and glycal based bolaforms WRT biorefinery process streams and the use of biobased products, our interest is in using carbos to make bolaforms. As shown on the previous slide, there are some examples in literature, but probably the most extensively studied materials are those prepared by Shimizu and Masuda, possessing glucose or galactose headgroups linked by a long amide containing chain. The synthesis of these materials is carried out by formation of the peracetylated glucosyl bromide, treatment with sodium azide, reduction, and linking of the amino group with the corresponding acid chloride. Removal of the acetate groups with NaOMe gives the bolaform, which undergoes self assembly. Shimizu and Masuda have done considerable investigation of the self assembly process of these materials, and the hydrogen bonding network that appears to hold them together. The downside for these materials is that the approach is not as flexible, synthetically, as it could be. We have been investigating the synthesis of bolaforms using a carbohydrate derivative, glycals, as the starting material. Our hypothesis was that glycal based bolaforms would give much more synthetically flexible materials, more well differentiated hydroxyl groups, and additional functionality in the form of the double bond, either for more structural modification, or to aid in self assembly through pi-pi stacking. Process offers considerable versatility. Introduction of a single double bond into the structure looks trivial, but from a synthesis standpoint, it offers a great handle for new transformations. From a biorefinery standpoint, we could also see these as being made from sugar and fatty acid. Completely renewable.WRT biorefinery process streams and the use of biobased products, our interest is in using carbos to make bolaforms. As shown on the previous slide, there are some examples in literature, but probably the most extensively studied materials are those prepared by Shimizu and Masuda, possessing glucose or galactose headgroups linked by a long amide containing chain. The synthesis of these materials is carried out by formation of the peracetylated glucosyl bromide, treatment with sodium azide, reduction, and linking of the amino group with the corresponding acid chloride. Removal of the acetate groups with NaOMe gives the bolaform, which undergoes self assembly. Shimizu and Masuda have done considerable investigation of the self assembly process of these materials, and the hydrogen bonding network that appears to hold them together. The downside for these materials is that the approach is not as flexible, synthetically, as it could be. We have been investigating the synthesis of bolaforms using a carbohydrate derivative, glycals, as the starting material. Our hypothesis was that glycal based bolaforms would give much more synthetically flexible materials, more well differentiated hydroxyl groups, and additional functionality in the form of the double bond, either for more structural modification, or to aid in self assembly through pi-pi stacking. Process offers considerable versatility. Introduction of a single double bond into the structure looks trivial, but from a synthesis standpoint, it offers a great handle for new transformations. From a biorefinery standpoint, we could also see these as being made from sugar and fatty acid. Completely renewable.

17. Glycal Based Bolaform Research Schematic These compounds form the basis of a larger matrix of opportunities. We assumed, for example, that they would undergo self assembly to form membranes. However, the presence of different structural features within the headgroups allows access to a number of different features. For example, we can change the headgroup structure fairly easily. This could begin to develop correlations between bolaform structure and the nanoscale structure that they ultimately form. The presence of the double bond within the headgroup could also lead to covalent linkages between bolaform molecules allowing stabilization of the nanoscale structure. The presence of ligating groups from the sugars suggest the possibility of coordinating metals, making these a way to assemble highly ordered catalysts.These compounds form the basis of a larger matrix of opportunities. We assumed, for example, that they would undergo self assembly to form membranes. However, the presence of different structural features within the headgroups allows access to a number of different features. For example, we can change the headgroup structure fairly easily. This could begin to develop correlations between bolaform structure and the nanoscale structure that they ultimately form. The presence of the double bond within the headgroup could also lead to covalent linkages between bolaform molecules allowing stabilization of the nanoscale structure. The presence of ligating groups from the sugars suggest the possibility of coordinating metals, making these a way to assemble highly ordered catalysts.

18. Ferrier Bolaform Synthesis Thus, our approach to synthesis uses a well known, characteristic reaction of glycals�the Ferrier reaction. Rxn proceeds by treating glycal with a Lewis acid catalyst, in this case, we use catalytic iodine. Forms a stabilized oxonium ion. The cation is well known to undergo reaction with a variety of nucleophiles at the anomeric position. In this case, we add a diol which incorporates the headgroups, and as the reaction proceeds, we can observe the formation of the intermediate monoadduct.. The acetate groups are removed under Zemplen conditions to give the final bolaform. We�ve carried out this reaction with three glycals so far. TAG is commercially available, and we have synthesized the corresponding xylal and galactal using literature procedures�conversion of the peracetate to the glycosyl bromide, and reductive olefin formation with Zn. I point out these synthesis to also indicate that they are multistep, and probably not ideal in the long term. However, we plan to investigate much more direct approaches to these materials based on work coming out of Kevin Gable�s group at Oregon State. He has developed some Re based systems that can be used for bis-dehydroxylation of diols to give olefins. Such a catalytic approach would be a much more direct method for converting biomass carbohydrates to glycals.Thus, our approach to synthesis uses a well known, characteristic reaction of glycals�the Ferrier reaction. Rxn proceeds by treating glycal with a Lewis acid catalyst, in this case, we use catalytic iodine. Forms a stabilized oxonium ion. The cation is well known to undergo reaction with a variety of nucleophiles at the anomeric position. In this case, we add a diol which incorporates the headgroups, and as the reaction proceeds, we can observe the formation of the intermediate monoadduct.. The acetate groups are removed under Zemplen conditions to give the final bolaform. We�ve carried out this reaction with three glycals so far. TAG is commercially available, and we have synthesized the corresponding xylal and galactal using literature procedures�conversion of the peracetate to the glycosyl bromide, and reductive olefin formation with Zn. I point out these synthesis to also indicate that they are multistep, and probably not ideal in the long term. However, we plan to investigate much more direct approaches to these materials based on work coming out of Kevin Gable�s group at Oregon State. He has developed some Re based systems that can be used for bis-dehydroxylation of diols to give olefins. Such a catalytic approach would be a much more direct method for converting biomass carbohydrates to glycals.

19. Bolaform Synthesis Summary Summary of transformations. Have looked at synthesis of several materials following the procedure at the top. Most of our syntheses have been carried out with triacetylglucal, and conversion to the bolaform acetate proceeds in good yield until we reach a C18 chain. We�ve pushed around the syntheses a little with TAG, and have prepared an unsymmetrical bolaform through addition of the saturated alcohol, also derived from TAG. And by incorporating an olefin metathesis step, we can get to a bolaform incorporating a double bond in the linking chain. We can also carry out the synthesis with the galactal and xylal in the same way. Currently, the drawback to this approach is the stereochemistry of the final product. The reaction with TAG is generally alpha-selective, with the ratio in these reactions being about 7 or 8:1. As we move to other glycals, the change in headgroup stereochemistry is reflected in the stereoselectivity of the Ferrier reaction. The reaction with galactal leads only to the alpha isomer since the beta side is crowded by the acetates, but in low yield. Early work by Ferrier suggested that glycals unable to experience stabilization of the intermediate carbonium ion by the C4 acetate proceeds in low yield. There is an equal amount of acetylation as a side product. Reaction of the xylal under these conditions gives a fair yield of product, but we observe formation of all three isomers as a result of lower steric control by the acetyl groups. These isomers can be separated by chromatography on Si gel.Summary of transformations. Have looked at synthesis of several materials following the procedure at the top. Most of our syntheses have been carried out with triacetylglucal, and conversion to the bolaform acetate proceeds in good yield until we reach a C18 chain. We�ve pushed around the syntheses a little with TAG, and have prepared an unsymmetrical bolaform through addition of the saturated alcohol, also derived from TAG. And by incorporating an olefin metathesis step, we can get to a bolaform incorporating a double bond in the linking chain. We can also carry out the synthesis with the galactal and xylal in the same way. Currently, the drawback to this approach is the stereochemistry of the final product. The reaction with TAG is generally alpha-selective, with the ratio in these reactions being about 7 or 8:1. As we move to other glycals, the change in headgroup stereochemistry is reflected in the stereoselectivity of the Ferrier reaction. The reaction with galactal leads only to the alpha isomer since the beta side is crowded by the acetates, but in low yield. Early work by Ferrier suggested that glycals unable to experience stabilization of the intermediate carbonium ion by the C4 acetate proceeds in low yield. There is an equal amount of acetylation as a side product. Reaction of the xylal under these conditions gives a fair yield of product, but we observe formation of all three isomers as a result of lower steric control by the acetyl groups. These isomers can be separated by chromatography on Si gel.

20. TEM Images of Nanostructures We have examined the assembly behavior of the glucal version of materials, and our initial results suggest that self assembly does occur. For example, the materials can be dissolved in 1:1 dioxane/water at about 15 mmolar, and stained with uranyl acetate. The resulting material shows assembly into long, tubular, fiber-like materials. The bar is 200 nm, so these structures are quite long. In other images from the TEM, we also observe the formation of spheres. However, these self assembly processes are far from predictable. For example, they appear to have a very strong dependence on the concentration and method of solution preparation. As we remove hydrophilic groups from the carbohydrates, the water solubility drops, and there appears to be a very fine line between assembly into tubules, and further large scale aggregation into crystals, and precipitation. We have also observed the ability of these materials to form long, visible fibers from dioxane/water solution. This process is still under active investigation. We have examined the assembly behavior of the glucal version of materials, and our initial results suggest that self assembly does occur. For example, the materials can be dissolved in 1:1 dioxane/water at about 15 mmolar, and stained with uranyl acetate. The resulting material shows assembly into long, tubular, fiber-like materials. The bar is 200 nm, so these structures are quite long. In other images from the TEM, we also observe the formation of spheres. However, these self assembly processes are far from predictable. For example, they appear to have a very strong dependence on the concentration and method of solution preparation. As we remove hydrophilic groups from the carbohydrates, the water solubility drops, and there appears to be a very fine line between assembly into tubules, and further large scale aggregation into crystals, and precipitation. We have also observed the ability of these materials to form long, visible fibers from dioxane/water solution. This process is still under active investigation.

21. Hypothetical Assembly Process Thus, since these undergo a more unpredictable self assembly, we�re trying to figure out why. An obvious hypothesis is that we have a much less robust intermolecular, noncovalent network. For example, the mechanism of assembly leading to tubes postulated by Masuda and Shimizu is shown here. A process of building up, through a network of H-bonds. And their x-ray work suggests a very strong network. If you just look at the proposed OH network, there are three reasonable links between sugar units. When you go to our systems, we�ve lose two of those, at least if one considers an alignment similar to M/S. However, we can also postulat other noncovalent alignments, such as shown on the lower right. We are in the process of trying to discern the alignment that�s observed in our systems. DESCRIBE the addition of pi-stacking�generally considered weaker than H-bonding (e. g., Whitesides review), but still a force. Alternatively, one can model antiparallel, and perhaps get a larger number of H-bonds. The mechanism of tube formation by these materials has been examined by Shimizu for fully saturated materials, and is described in the cartoon in the upper left. It is a process of continually building up a structure. Their group has also examined the hydrogen bonding network holding their systems together using xray, and finds that the sugars interact as shown. Now�when we move to the glycals, the directly analogous bonding mechanism would not be nearly as strong as some of the key OH groups have been lost. Moreover, we do not have the additional amide linkage present in M/S molecules. Their systems possess the potential for peptide-like intermolecular H-bonding, which is an extremely strong interaction. Thus, we are trying to determine what the bonding structure looks like. We do not yet know the nature of the assembly process for these materials, but some hypothetical bonding structures might include pi stacking with the olefins. Alternatively, the groups might adopt a parallel or antiparallel orientation.Thus, since these undergo a more unpredictable self assembly, we�re trying to figure out why. An obvious hypothesis is that we have a much less robust intermolecular, noncovalent network. For example, the mechanism of assembly leading to tubes postulated by Masuda and Shimizu is shown here. A process of building up, through a network of H-bonds. And their x-ray work suggests a very strong network. If you just look at the proposed OH network, there are three reasonable links between sugar units. When you go to our systems, we�ve lose two of those, at least if one considers an alignment similar to M/S. However, we can also postulat other noncovalent alignments, such as shown on the lower right. We are in the process of trying to discern the alignment that�s observed in our systems. DESCRIBE the addition of pi-stacking�generally considered weaker than H-bonding (e. g., Whitesides review), but still a force. Alternatively, one can model antiparallel, and perhaps get a larger number of H-bonds. The mechanism of tube formation by these materials has been examined by Shimizu for fully saturated materials, and is described in the cartoon in the upper left. It is a process of continually building up a structure. Their group has also examined the hydrogen bonding network holding their systems together using xray, and finds that the sugars interact as shown. Now�when we move to the glycals, the directly analogous bonding mechanism would not be nearly as strong as some of the key OH groups have been lost. Moreover, we do not have the additional amide linkage present in M/S molecules. Their systems possess the potential for peptide-like intermolecular H-bonding, which is an extremely strong interaction. Thus, we are trying to determine what the bonding structure looks like. We do not yet know the nature of the assembly process for these materials, but some hypothetical bonding structures might include pi stacking with the olefins. Alternatively, the groups might adopt a parallel or antiparallel orientation.

22. X-ray Structures of Bolaform Crystals Now, we just got the xray structures back last week, and our preliminary observations at least about the solid state show some interesting features. The relative location of the part that sees the hydrophobic interactions is not significantly different in structure when the stereochemistry at the anomeric center is inverted. Thus, the �outside� of the nanostructure and the hydrogen bonding network that it exhibits should be about the same. That appears to be the case. Note the distortion in the double bond in the solid state. Also, we find some very interesting solid state correlations between our systems and those reported in the literature. For example, when the headgroup is of the glucose conformation, it can adopt either this semi-flat structure, or the one with the more severe bend, depending on whether the starting individual molecule is in the alpha or the beta conformation. Alternatively, when we change to the galactal conformation, a parallel orientation is observed. These examples are exactly what is observed in the galactal and glucal analogs shown. Now, we just got the xray structures back last week, and our preliminary observations at least about the solid state show some interesting features. The relative location of the part that sees the hydrophobic interactions is not significantly different in structure when the stereochemistry at the anomeric center is inverted. Thus, the �outside� of the nanostructure and the hydrogen bonding network that it exhibits should be about the same. That appears to be the case. Note the distortion in the double bond in the solid state. Also, we find some very interesting solid state correlations between our systems and those reported in the literature. For example, when the headgroup is of the glucose conformation, it can adopt either this semi-flat structure, or the one with the more severe bend, depending on whether the starting individual molecule is in the alpha or the beta conformation. Alternatively, when we change to the galactal conformation, a parallel orientation is observed. These examples are exactly what is observed in the galactal and glucal analogs shown.

23. Comparative Hydrogen Bonding Networks We can also isolate the nature of the hydrogen bonding network in these systems, shown here. As expected, our systems show a much lower number of bonding opportunities. Yet they still assemble. Thus, it appears that as crystallization is approached, these forces are sufficient to form ordered crystal shapes that depend only on the stereochemistry of the headgroups�this seems to be an important force in this system. However, one could imagine that self assembly in solution might be much more dependent on the number of good intermolecular interactions available. Thus, our systems may be lacking in H-bonds. The pi bonds are also important, but their contribution is still unclear at this point.We can also isolate the nature of the hydrogen bonding network in these systems, shown here. As expected, our systems show a much lower number of bonding opportunities. Yet they still assemble. Thus, it appears that as crystallization is approached, these forces are sufficient to form ordered crystal shapes that depend only on the stereochemistry of the headgroups�this seems to be an important force in this system. However, one could imagine that self assembly in solution might be much more dependent on the number of good intermolecular interactions available. Thus, our systems may be lacking in H-bonds. The pi bonds are also important, but their contribution is still unclear at this point.

24. Disaccharide Bolaform Headgroups But the other approach is experimental, trying to figure out how we might improve the headgroup interaction. One approach is to change the electronics of the headgroup. To potentially improve hydrophilic interaction between headgroups, also investigating disaccharides. Very preliminary, but we�re starting with the four potential headgroups shown here, all of which are reasonable materials to be found in a biorefinery�cellobiose and xylobiose, of course, will be available from enzymatic hydrolysis processes during EtOH production. Started with lactose and maltose, strictly because that what we had in the lab at the time.But the other approach is experimental, trying to figure out how we might improve the headgroup interaction. One approach is to change the electronics of the headgroup. To potentially improve hydrophilic interaction between headgroups, also investigating disaccharides. Very preliminary, but we�re starting with the four potential headgroups shown here, all of which are reasonable materials to be found in a biorefinery�cellobiose and xylobiose, of course, will be available from enzymatic hydrolysis processes during EtOH production. Started with lactose and maltose, strictly because that what we had in the lab at the time.

25. Chemical Stabilization and Bioactive Materials Other approach: put a moderately self assembling system in the presence of a more organized system and see if organizational information can be transferred. Now, the self assembly of these materials by themselves is still being perfected and investigated, and as I indicated, the structures still appear somewhat fragile, and not yet completely within our control. Thus, we are also looking to see what happens if we induce self assembly in the presence of a more ordered material. Specifically, we have been looking at the interaction of our bolaforms with cellulose in solution. Now�in our reaction schematic, I also indicated how we wanted to investigate various stabilization methods for the larger scale structures that might arise from bolaform self assembly. The strong influence of hydrogen bonding on the structures adopted during assembly suggested that interaction of the bolaforms with biopolymers such as cellulose could serve to template the bolaforms, leading to new types of nanoscale assemblies. The use of cellulose for patterning has been reported by Kondo�s group. They have examined the use of a patterned cellulose, nematic ordered cellulose, as a template for laying down of microbial cellulose by Valonia species. In their work they find that the NOC serves as a pattern for the microbes to follow. Thus, we have started to look at how the bolaforms might interact with cellulose in solution.Other approach: put a moderately self assembling system in the presence of a more organized system and see if organizational information can be transferred. Now, the self assembly of these materials by themselves is still being perfected and investigated, and as I indicated, the structures still appear somewhat fragile, and not yet completely within our control. Thus, we are also looking to see what happens if we induce self assembly in the presence of a more ordered material. Specifically, we have been looking at the interaction of our bolaforms with cellulose in solution. Now�in our reaction schematic, I also indicated how we wanted to investigate various stabilization methods for the larger scale structures that might arise from bolaform self assembly. The strong influence of hydrogen bonding on the structures adopted during assembly suggested that interaction of the bolaforms with biopolymers such as cellulose could serve to template the bolaforms, leading to new types of nanoscale assemblies. The use of cellulose for patterning has been reported by Kondo�s group. They have examined the use of a patterned cellulose, nematic ordered cellulose, as a template for laying down of microbial cellulose by Valonia species. In their work they find that the NOC serves as a pattern for the microbes to follow. Thus, we have started to look at how the bolaforms might interact with cellulose in solution.

26. Bolaform Crystal Formation in Presence of Cellulose Now�these results are very recent, and therefore, there is much more that we don�t know than what we do. However, the approach we took was to dissolve cellulose in a standard 8% LiCl/DMAc solution, and add various concentrations of bolaform to this solution. In some instances, we cast films of these solutions, and in others, we simply placed a drop of the solution on a microscope slide and allowed the drop to stand, either in air, or under slower evaporation conditions by placing a coverslip over the drop. In the upper left is the result from a drop of bolaform in DMAc/LiCl in the absence of cellulose (avicel). Upon standing, a large number of individual crystals are seen to form. However, when we carry out the same procedure in the presence of dissolved cellulose, we observe what looks like a much greater level of organization during crystal formation. In the lower left, we see the transition from the edge of a drop of solution where evaporation may take place more rapidly, leading to a greater proportion of small crystals, and then moving into the bulk of the drop, where a greater proportion of more organized structures are seen. What we are trying to determine is the relative location of the cellulose polymer and the bolaform in these systems. For example, is the �trunk� of these systems the result of bola interacting with cellulose, and are the branches bolaform by itself, finding various nucleation sites along the primary trunk? We have carried out FT-IR microscopy of these systems, and have determined that the material making up these structures is indeed bolaform. We intend to use FTIR in combination with PCA in order to deconvolute overlapping cellulose/bola spectra and better determine the location of the cellulose.Now�these results are very recent, and therefore, there is much more that we don�t know than what we do. However, the approach we took was to dissolve cellulose in a standard 8% LiCl/DMAc solution, and add various concentrations of bolaform to this solution. In some instances, we cast films of these solutions, and in others, we simply placed a drop of the solution on a microscope slide and allowed the drop to stand, either in air, or under slower evaporation conditions by placing a coverslip over the drop. In the upper left is the result from a drop of bolaform in DMAc/LiCl in the absence of cellulose (avicel). Upon standing, a large number of individual crystals are seen to form. However, when we carry out the same procedure in the presence of dissolved cellulose, we observe what looks like a much greater level of organization during crystal formation. In the lower left, we see the transition from the edge of a drop of solution where evaporation may take place more rapidly, leading to a greater proportion of small crystals, and then moving into the bulk of the drop, where a greater proportion of more organized structures are seen. What we are trying to determine is the relative location of the cellulose polymer and the bolaform in these systems. For example, is the �trunk� of these systems the result of bola interacting with cellulose, and are the branches bolaform by itself, finding various nucleation sites along the primary trunk? We have carried out FT-IR microscopy of these systems, and have determined that the material making up these structures is indeed bolaform. We intend to use FTIR in combination with PCA in order to deconvolute overlapping cellulose/bola spectra and better determine the location of the cellulose.

27. SEM of Cellulose Films

28. AFM Images of Bola/Cellulose Film Upon closer examination of these materials by AFM, we get suggestions of higher levels of organization in the presence of bolaform. The AFM on the left are scans of an avicel film in the absence of bolaform. When bola is added to the film, it looks to have some stratification, running in a pattern from top L to bottom R. It also appears to be smoother with a lower roughness value. A similar increase in smoothness is observed in the SEM as if the bolaform might be filling in some of the surface irregularities. Ordering of crystallizable materials in the presence of cellulose is precedented. For example, cellulose is used to induce organized crystallization of CaCO3 in the formation of bone substitutes. It has also been used to modify the crystallization of acetaminophen. Cellulose derivatives, such as HEC, promotes the organization of CdS into long nanorods, as opposed to CdS spheres.Upon closer examination of these materials by AFM, we get suggestions of higher levels of organization in the presence of bolaform. The AFM on the left are scans of an avicel film in the absence of bolaform. When bola is added to the film, it looks to have some stratification, running in a pattern from top L to bottom R. It also appears to be smoother with a lower roughness value. A similar increase in smoothness is observed in the SEM as if the bolaform might be filling in some of the surface irregularities. Ordering of crystallizable materials in the presence of cellulose is precedented. For example, cellulose is used to induce organized crystallization of CaCO3 in the formation of bone substitutes. It has also been used to modify the crystallization of acetaminophen. Cellulose derivatives, such as HEC, promotes the organization of CdS into long nanorods, as opposed to CdS spheres.

29. Alignment of Carbohydrates Now, as I indicated, these are quite recent results, and I don�t want to move too far into speculation. However, we now hope to begin understanding what is going on at the molecular level between the bolaforms and dissolved cellulose. As I�ve shown in this slide, using cellobiose as a cellulose surrogate, we can begin to design possible H-bonding schemes, and incorporate them into larger scale structures. For example, does pi-bonding play a significant role? How are the hydrophobic chains aligning themselves? What does the overall H-bonding network look like, and can it be controlled? New nanostructural constructs from the bolaforms. For example: organization of saccharides in solution. Cellobiose as an example�what does the H-bonding network look like? Can it be controlled? What shapes are the result of self assembly? Can initial H-bonding networks undergo enhancement by stacking and assembly into larger arrays? All structures are highly speculative, but our hope is to observe organization of various carbohydrates by the bolaforms, and the development of new biobased nanostructures as a result. Ultimately, we will examine a range of carbohydrate/bolaform systems to see what happens as one transitions from the monosaccharide products of the biorefinery through to the oligo- and polysaccharides.Now, as I indicated, these are quite recent results, and I don�t want to move too far into speculation. However, we now hope to begin understanding what is going on at the molecular level between the bolaforms and dissolved cellulose. As I�ve shown in this slide, using cellobiose as a cellulose surrogate, we can begin to design possible H-bonding schemes, and incorporate them into larger scale structures. For example, does pi-bonding play a significant role? How are the hydrophobic chains aligning themselves? What does the overall H-bonding network look like, and can it be controlled? New nanostructural constructs from the bolaforms. For example: organization of saccharides in solution. Cellobiose as an example�what does the H-bonding network look like? Can it be controlled? What shapes are the result of self assembly? Can initial H-bonding networks undergo enhancement by stacking and assembly into larger arrays? All structures are highly speculative, but our hope is to observe organization of various carbohydrates by the bolaforms, and the development of new biobased nanostructures as a result. Ultimately, we will examine a range of carbohydrate/bolaform systems to see what happens as one transitions from the monosaccharide products of the biorefinery through to the oligo- and polysaccharides.

30. Conclusions and Acknowledgements Renewable sources of carbon offer unique opportunities for the production of chemicals, fuels and materials. The forest biorefinery of the future must integrate new product opportunities with their traditional product lines Carbohydrate based bolaforms could offer an entry into the rapidly growing field of nanostructural materials, but more work is needed to control the process Interaction of bolaforms with natural polymers may lead to new families of uniquely patterned materials Thanks! To Thomas Elder, David Thompson, John Dunlap, Sebastien Vidal, Joseph Bullock Funding: USDA/NRI