Every once in a while, a conference comes along that is truly inspiring. Yesterday's Green Processing Symposium was like that, bringing together a group of people who are not only extremely smart but very altruistic---chemists who have dedicated their lives to finding solutions to environmental issues in industry and to implementing these solutions, slowly eroding the negative mindset and resistance to change that has paralyzed some corners of the drug industry. Some of them were motivated as children. Yale professor Scott Miller, for instance, recalled when Lake Erie, a favorite childhood swimming spot, caught fire. Apart from dutiful coverage of the President's Green Chemistry award, the mainstream press gives them far less coverage than it gives the Greenpeace activists, who provide better photo ops when they hang upside down from oil rigs (wearing PVC rain slickers) to protest petrochemical and plastics production. Not that Greenpeace is bad, but these "green" chemists and engineers are taking far more concrete steps to address environmental problems, and their work truly has a lasting impact. If the ripple effect would only speed up, and if FDA would support this work more actively (how many existing commercial drug manufacturing processes couldn't be improved by changing solvents, or tweaking a few process steps to reduce complexity and improve control----oh, no, I forgot----there'd be revalidation. Forget about it...But aren't we dealing with an FDA that supports process understanding and control? Like I said, forget about it...) Quality by Design is the perfect tool for inculcating green values into drug development, and, by some accounts, the Agency is becoming much more supportive of green product development efforts. Not everyone agrees, though. Said one conference attendee, who asked to remain anonymous, "FDA is orthogonal to green chemistry. It's only focused on the safety and efficacy of the product, and QbD is focused only on patient safety." How about the safety of patients living near plants that may be releasing unnecessarily high levels of toxic compounds? Not my job....OK, so FDA's got enough to cope with right now....but how about thinking outside the box, or the "path"? After an introduction by Paul Anastas, Director for Yale's Center for Green Chemistry and Engineering, John Warner, President and CTO of the Warner Babcock institute for Green Chemistry (as well as the nonprofit group, Beyond Benign, more information on which you'll find here) discussed the concept of non-covalent derivatization (NCD, which is also, reportedly, on his license plate). He discussed work at Polaroid years ago involving hydroquinones. Some lessons here for any researcher in any industry: when he started his career as head of exploratory research, he went directly to manufacturing and asked "what keeps you up at night?" Problem was the fact that film had fairly short shelf life, so it was a question of increasing stability by controlling the rate of dissolution. Very applicable to pharma development... Think Entropy, Not Enthalpy After discussing the chemistry behind noncovalent derivatization, Mr. Warner discussed the fact that too much of industrial chemistry today is focused on the concept of enthalpy, when, instead, it should be paying more attention to entropy, and discovering the triggers for system stability or instability. He also discussed Rene Thom and the tipping point as it applies here. No chemical formulas or equations here....it's just a blog, these are hastily written (and my last organic chemistry course took place 20 years ago!)... in general, the first part of the program went entirely over my head...too many compounds on too many slides, moving too quickly. But he also discussed Steric accumulation and the fact that solubility and chemical properties can be dictated without making or breaking a chemical bond....he then went on to discuss work at ChemMotif and NIH that led to the design of a cyanide detector, as well as work on metal oxide semiconductor coatings which allowed coating to occur at room temperature (instead of 450 degrees C)...one of his students coated plastic LEDs with titanium dioxide, creating a water-purification device. Warner then went on to discuss his work in thymine photopolymers, which won a Presidential Green Chemistry award in 2005, and how he was inspired by PUVA phototherapy (to treat a skin condition) to look into this application, which allows conductive polymers to be coated on fibers, textiles (and even hair curling and hair "dyes" that would eliminate toxic chemicals from the formulas---and avoid the "purple" hues that can come from some formulas that claim to be natural-materials based. ) He wrapped up the presentation by touching on implications of work with thermphilic enzymes... India and China Training Students in Green Chemistry One attendee asked about green chemistry's impact on the developing world, given the trend to outsource manufacturing to parts of the world with less stringent environmental regulations. Mr. Babcock mentioned that U.S. education and workforce training needed to advance environmental chemistry, and the fact that India is now requiring that all students of chemistry and allied subjects must now complete a green chemistry curriculum. China is also moving in that direction...slow progress, but in 20 years, where will they be? And where will we be? Much food for thought, in any case. The next speaker, Tak Hang Chan, Professor Emeritus at McGill, discussed ionic liquids and their use, not as solvents but as supports for organic synthesis to improve phase separation and purification. One of the most interesting potential applications was in gene therapy developing a synthetic small interfering RNA (SiRNA----time to start reading up on the subject) that would greatly decrease the cost of synthesizing the material at higher volumes. ScinoPharm and Merck Frost are among those who have worked on some of these projects. Next up was Yasuhiro Uozumi from Japan's Institute for Molecular Science, whose work has focused on using amphiphilic polystyrene-polethylene glycol resin supported transition metal complexes...in asymmetric Pi allylic substitution, it raised yields significantly. Yale's Scott Miller then discussed asymmetric catalysis and using alpha amino acides and their peptide derivatives to catalyze enantioselective and regioselective processes. Quite a morning. More later.