Archive for the ‘physical chemistry’ Category:
Puzzling polymorphs
by Chemjobber on Jun 07 2010 (10691 Views)
Polymorphism is a common and sorta crazy issue in pharmaceutical process chemistry. Basically put, a drug molecule in the solid state can have multiple crystal forms. Different impurity profiles and different crystallization techniques (solvents, heating/cooling rates) can produce different polymorphs, which can have wildly different physical properties and bioavailabilities. A famous story of troublesome polymorphism is Abbott’s ritonavir, where in the middle of manufacturing for sale (not during the R&D phase!), a new, much less soluble polymorph started showing up in batches. Moreover, once the new polymorph showed up, it was very difficult to generate the previous polymorph. Even crazier, a team of scientists went to another plant in Italy where the process was still working as desired, and soon after the team left, the new polymorph appeared. It took a crash program to understand which conditions were generating the new crystal form to get it under control.
A recent article by Pradash et al. in Organic Process Research and Development illustrates the problems of polymorphism similarly: once the authors determined that there was another crystal form (‘Form A’) than the original (‘Form B’), they undertook a screening process (looking at varieties of solvent and crystallization techniques) to find other polymorphs. Interestingly, once they discovered a new polymorph (‘Form C’), they found that it was impossible to generate Form B in their laboratories. They selected Form C for its physical properties and moved it into the pilot plant; lo, they then found Form D. This new crystal form began predominating and “those seeded crystallization processes that consistently produced Forms A and C started to produce predominately Form D in the laboratory.” (Click on image to see pictures of the polymorphs and the structure itself.)
When I read these accounts, I am filled with admiration for pharmaceutical process chemists, the interesting science that they get to do and the vast reserves of patience and sangfroid they must have. Chemistry (and manufacturing chemistry, especially!) is based on reproducibility and consistency; when issues arise, I suspect that there is a great deal of checking and double-checking to make sure that “this is really happening to us.” Also, I can’t help but wonder if those process chemists, when these issues are discovered, wonder if the laws of the physical universe are being temporarily suspended and some Loki-like diety is having its way with them.
Electroneutrality is dead?
by mitch on Sep 03 2009 (4948 Views)
Gerald Pollack
That is the highly controversial claim made by Kate Ovchinnikova and Gerald Pollack in Langmuir earlier this year.[Langmuir] Electroneutrality is a guiding principal in electrochemistry and is a method to understanding electrolytic cells (Pt electrodes in dilute aqueous NaCl solutions). It stipulates that any charge imbalance across an electrochemical system is quickly (~ns) balanced by the salt present in the water being driven by the electric field in such a way to neutralize that charge imbalance. Thus the need for salt bridges and all that wonderful G-chem stuff we have learned. There is even a cool little applet you can play with electroneutrality by the Harvey Project. When I tried to sit down with electrochemists to discuss the claims by O&P they quickly dismissed them out of hand after reading the beginning of their paper. So the big question is, did O&P stumble across something amazing or did they spectacularly overstate the results of their experiment.
I can summarize their paper succinctly:
- Insert electrodes into electrolytic cell
- Turn on power supply
- Disconnect the electrodes from the circuit
- Remove the bridge between beakers
- Reconnect electrodes to measure residual charge in the two beakers.
The design seems thoughtful enough, but before I get into the merits of their results I need to take time to mention a few gems in their paper. Here is a quote from them.
Bubble formation occurred in all experiments (n > 20), although position and growth rate were inconsistent. In most cases, formation began during the charging phase and continued through discharge. Characteristics of bubble formation were not pursued in any detail, but may warrant future study.
But it doesn’t warrant further study, all chemists know where their bubbles came from.
An other eye catcher is that they didn’t use a standard electrochemical setup. They used my trusty NI USB-6009, I know that product well as a chunk of my thesis was acquired with it. It doesn’t make the experiment invalid, but why use crap when you are trying to disprove such a time honored concept as electroneutrality. Maz and I know from experience that the USB-6009 floats if their isn’t a sufficient load on it or if their isn’t an appreciable external voltage.
Here is a quote from them contemplating that HCl solutions have an overall positive charge.
One might speculate, for example, whether ordinary acidic solutions, which have low pH, might contain net positive charge, while ordinary basic solutions might contain net negative charge.
So far everything has been “quirky”, it isn’t until the end when you perceive something really odd.
Water appears able to adopt two structural networks that have mirror symmetry to one another. The fact that these networks are macro phenomena deserves further study.
A second and related issue is the potential for disturbance of these structural networks. It is now established that when water is left standing for long periods, it develops thixotropic properties, implying macrostructure.7 Such macrostructure is expected to be fragile. The fact that removing and inserting electrodes did not apparently ruin the charge-containing structure implies that, once formed, the structural network can re-form rather readily. This is an additional subject requiring further study.
7:Vybiral, B. Water and the Cell; Pollack, G. H., Cameron, I., Wheatley, D., Eds.; Springer: New York, 2006; pp 299-314.
It is with that last statement you say to yourself, “Oh, I get it. This is a homeopathy paper.” Water being able to adopt structures of the solutes that were dissolved in it is a hallmark of the quackery that is homeopathy. O&P’s claim isn’t that bold, but it has hints of the same idea. Claiming macrostructures (~mm) of water that extend past the picosecond domain is absurd.
Although I haven’t discussed the results of their paper, would you really trust it anyways?
Horacio Corti and Agustin Colussi have done an excellent job dissecting the technical irregularities of the paper and I encourage you to read their comments on the article (link below). If you come to a different conclusion or find me in error, please leave a comment and join the discussion.
Links
- Can Water Store Charge? (Ovchinnikova and Pollack)
- Do Concentration Cells Store Charge in Water? Comment on Can Water Store Charge? (Corti and Colussi)
- Reply to Comment on Can Water Store Charge? (Ovchinnikova and Pollack)
- Response to Reply to Comment on Can Water Store Charge (Corti and Colussi)
Mitch
Survivor: Mechanisms (now accepting logo submissions)
by azmanam on May 13 2009 (3720 Views)
I read an interesting article in May’s issue of J. Chem. Ed. titled “Can Reaction Mechanisms Be Proven?” by Allen Buskirk and Hediyeh Baradaran of BYU. Intriguing. So I pop open the pdf and a Note from the Editor is boxed at the top of the page before the article starts. It says:
“Can Reaction Mechanisms Be Proven?” generated spirited responses from its reviewers. The reviews were approximately evenly divided, and all were of very high quality. The authors agreed with the editor’s proposal that the reviewers convert their reviews into rebuttals or affirmations of the authors’ position for publication along with the article, which has been revised based on the reviews. Most agreed to such a process and their comments appear here. We hope that publication of this paper and well-reasoned rebuttals such as those provided here will initiate a wide-ranging discussion. JCE will provide an online forum for further discussion of the issue. Our hope is that both faculty and students will contribute their opinions and ideas to this discussion. -JWM
Huh. You don’t usually hear about that happening too often. So now I had to read the article. It’s pretty fascinating, and I encourage you to read it all. I’ll summarize and give my thoughts below the jump
Chemical Kinetics of Valentine’s Day
by mitch on Feb 14 2009 (2069 Views)If the members of group A and group B want to form a union AB it can be described by the following chemical equation.
which will have a rate constant of
![R = k[\text{A}][\text{B}]](http://www.chemistry-blog.com/wp-content/cache/tex_28f4693d9084ed068131fecf0c0403e1.png)
Assuming this is an elementary process we can solve for the rate of this reaction by the introduction of a progress variable
.![x = ([\text{A}]_0 - [\text{A}]_t) = ([\text{B}]_0 - [\text{B}]_t)](http://www.chemistry-blog.com/wp-content/cache/tex_1a569b7767a71482677abf74b2d5a2ed.png)
Substituting
for 
yields…![\frac{dx}{dt} = k([\text{A}]_0 - x)([\text{B}]_0 - x)](http://www.chemistry-blog.com/wp-content/cache/tex_36c7da5540b190c9b4c01d9f0760abf9.png)
And to determine the time behavior we simply integrate.
![\int_{x(0)}^{x(t)} \frac{dx}{([\text{A}]_0 - x)([\text{B}]_0 - x)} = k\int_0^t dt](http://www.chemistry-blog.com/wp-content/cache/tex_8560cfb54fbf71ae0a949fc543430e57.png)
Using the method of partial fractions
![\int_0^x \frac{dx}{([\text{A}]_0 - [\text{B}]_0)([\text{B}]_0 - x)} - \int_0^x \frac{dx}{([\text{A}]_0 - [\text{B}]_0)([\text{A}]_0 - x)} = k\int_0^t dt](http://www.chemistry-blog.com/wp-content/cache/tex_26146d38223e35897c71283c41a8bda6.png)
Integrating…
![-\frac{1}{([\text{A}]_0 - [\text{B}]_0)}\ln\left([\text{B}]_0 - x\right)_0^x + \frac{1}{([\text{A}]_0 - [\text{B}]_0)}\ln\left([\text{A}]_0 - x\right)_0^x = kt](http://www.chemistry-blog.com/wp-content/cache/tex_d6effd623a37cf7b7dd55b3cc3d782ae.png)
Grouping…
![\frac{1}{([\text{A}]_0 - [\text{B}]_0)}\ln\left(\frac{([\text{A}]_0 - x)}{([\text{B}]_0 - x)}\right)_0^x = kt](http://www.chemistry-blog.com/wp-content/cache/tex_d8152c09373fe1f6d0c559d8d472c6e4.png)
Evaluating this from 0 to
![\frac{1}{([\text{A}]_0 - [\text{B}]_0)}\ln\left(\frac{([\text{A}]_0 - x)}{([\text{B}]_0 - x)}\right) - \frac{1}{([\text{A}]_0 - [\text{B}]_0)}\ln\left(\frac{([\text{A}]_0 - 0)}{([\text{B}]_0 - 0)}\right) = kt](http://www.chemistry-blog.com/wp-content/cache/tex_d61814c929059d52cb7f10231e6219a6.png)
![\frac{1}{([\text{A}]_0 - [\text{B}]_0)}\ln \left(\frac{([\text{A}]_0 - x)}{([\text{B}]_0 - x)}\right) - \frac{1}{([\text{A}]_0 - [\text{B}]_0)}\ln \left(\frac{[\text{A}]_0}{[\text{B}]_0}\right) = kt](http://www.chemistry-blog.com/wp-content/cache/tex_158b785f9eb0f95cadb34655edad5230.png)
Remembering that
![[\text{A}]_0 - x = [\text{A}]_t](http://www.chemistry-blog.com/wp-content/cache/tex_9251871aa5f4b6f1a43e50c96b932293.png)
![\frac{1}{([\text{A}]_0 - [\text{B}]_0)}\ln \left(\frac{[\text{A}]_t}{[\text{B}]_t} \right) - \frac{1}{([\text{A}]_0 - [\text{B}]_0)}\ln \left(\frac{[\text{A}]_0}{[\text{B}]_0}\right) = kt](http://www.chemistry-blog.com/wp-content/cache/tex_382977660a87d7a80c8e4334b04ef0c2.png)
Simplifying, we finally have an expression for the union of two reactive groups of people on Valentine’s day.
![\frac{1}{([\text{A}]_0 - [\text{B}]_0)}\ln \left(\frac{[\text{A}]_t[\text{B}]_0}{[\text{B}]_t[\text{A}]_0} \right) = kt](http://www.chemistry-blog.com/wp-content/cache/tex_6514b1d228abbf0f1b634928f1f59405.png)
May the rate constant (
) be large today!
Mitch
Light Powered Motor and Experiment Vlogging
by maz on Jul 01 2008 (2745 Views)Most of you probably read the last issue of C&EN with the spiffy carrot loving cover story (good for me because I love carrots, but have never tried those ugly-looking BetaSweets). Inside, however, there was an extremely interesting little article in the “Science and Technology Concentrates” about light-driven pulleys turning a plastic motor.
Now photo mobile polymer materials have been around for quite a while, at least from my perspective seeing as how I wasn’t even in highschool when the big Nature paper came out. Some might remember the Nature 1999 Sep 9;401(6749):152-5 Koumura et al. paper titled “Light-Driven monodirectional molecular rotor”. Although back then, the rotation was monodirectional around a C-C double bond in a chiral, helical alkene. It was activated by UV light or a change in temperature and the motor was based on light-induced cis-trans isomerizations that caused 180 degree rotations followed by thermally controlled helicity inversions, which basically nullified half a rotation. Four isomerizations resulted in 1 complete cycle.
Well this was pretty darn cool but we’ve come a long way since then. As expected, and as Koumura said, structurally modified chiral alkenes played the central role in the development of these molecular motors that were beginning to interest the MEMS people (MEMS stands for Micro-Electromechanical Systems…I am pretty sure).
In J Am Chem Soc. 2003 Dec 10;125(49):15076-86, ter Wiel MK et al. introduced the worlds smallest artificial light-driven motor using 28 carbon atoms and 24 hydrogen atoms.
It also had a dramatic speed increase over the original designs, at a whopping 18s half-life at the fastest step. Even if it wasn’t going to be turning any relevant loads any time soon, it was a dramatic improvement over the original concept 4 years earlier. Still, even though some clever O-chem tricks made the motor better, it still operated on the same 4-step cycle that Koumura’s did back in 99′. Even recently, in Org. Biomol. Chem., 2008, 6, 507 – 512, DOI: 10.1039/b715652a, Pollard et al. report on substituting naphthalene moieties for phenyl moieties, in order to better control the speed of the motors, and to enable the design and synthesis of more complex systems.
Meanwhile, the MEMS people came up with interesting designs similar to this:
“A five micron wide resin structure, with a shape resembling a lawn sprinkler, rotates when illuminated by a laser beam. Tiny rotors like this one may someday power micromechanical systems (MEMS), or twist molecules to measure their mechanical properties.” Reported by: Péter Galajda; Pál Ormos, Applied Physics Letters, 8 January, 2001.
There was quite a bit of work done focusing on creating rotors that responded to laser light, although the practical applications of such devices aren’t as numerous as the devices that…well don’t require a coherent, collimated, polarized light beam to operate. Or at least they weren’t until Peidong Yang’s came around with his nanolasers.
Unfortunately, all of these motors share the drawback of being unidirectional. It was until recently, with Ikeda’s et al. paper in Angew. Chem. Int. Ed. 2008, 47, 4986, that a very cool and new method for directly converting light into mechanical work. Basically they drew on the fact that azobenzene derivatives, when incorporated into liquid crystals, can have an isotropic phase transition induced isothermally by irradiation with UV light to cause trans–cis photoisomerization, and that the reverse transition can be induced by irratiation with visible light to cause cis-trans back-isomerization. This photoinduced phase transition
led to successfully reversible deformations of liquid crystal elastomers containing azobenzene chromophores just by changing the wavelength of the incident light.
Now this by itself doesn’t a motor make. There was one large problem: the liquid crystal elastomer had to be made into a film or “belt” for a motor. However, the LCE film by itself wasn’t mechanically strong enough and tended to crack after short light irradiation at high intensities. So to fix this issue, they simply laminated the LCE film with flexible polyethylene sheets. I love this type of simple solution to what could have been a convoluted problem. This is very much like what Mitch and I tend to do.
*Note that they did do a study of increasing light intensity and it’s correlation to the mechanical force generated by the film. They found that “the maximum force and the increment rate of the generated force are enhanced with an increase of the light intensity.”*
So what happened? Well check this out:
Thats right. That is an actual light-driven motor NOT on the micro-scale. The diameter of those pulleys are 10mm on the left and 3 mm on the right. Sure it isn’t going to be competing in any races at the moment, but it could still be amazingly useful in the future. Light, straight to DC? That would be pretty darn awesome.
PS. Tomorrow is the first day of the experiment Mitch and I are running. Since we can, we will be broadcasting the first live cyclotron experiment out over the interweb. This may be one of the first live nuclear physics experiments broadcasted. Other then that, it is just cool. SO we will have it up all 24 hours as a “live vlog”.
Feel free; hell feel obligated to stop by, leave a comment, chat, ask questions, offer constructive or destructive criticism, whatever. Maybe ACS will pick this up as a new way to present new research: present it as it happens! Live!!!
