Whither the protecting group?

Kudos to Phil Baran's group, who have just published in the journal Nature describing protecting-group (PG) free syntheses of members of the hapalindole, fischerindole, welwitindolinone and ambiguine families.
the ref: Nature 2007, 446, 404-408.
His group has published the enantioselective total synthesis of some of these compounds before (see, for instance, JACS 2005, 127, 15394-96.) but I'm guessing Nature deemed this worthy because of its unified application of a few big philosophies of organic synthesis (ie, atom economy and convergency) while trying to evaluate the pros and cons of going PG-free, as well as its overarching call for hearkening back to the early days, when men were men and syntheses were PG-free. That, and they optimized the routes to welwitindolinone and fischerindole to get higher yields.
So what is a protecting group? For organic chemists, they are a way of reining in the more unruly sections of the molecule you happen to be making. To be more specific, it's necessary to mask parts of the molecule that are likely to behave in some way other than what you'd like, or that refuse to "go along quietly" when some other part of your molecule needs attention.
For a great description, take a look here for Dylan Stiles' (aka Tenderbutton's) rather prescient article about the protecting group and some classic examples thereof.
Is the "PG-free way" really Mother Nature's way? If not, is her favorite protecting group the MOM group?
I think that some masked chemical reactivity exists in the biological world. I hope that my more scientifically inclined readers won't take offense at my stretching an analogy just a bit for the sake of a blog entry.
Take enzymes like proteases. Proteases break the bonds that link up the fundamental building blocks in proteins, and they're involved in many important roles in the body, from blood clotting to cell death. It's extremely important that proteases be exquisitely regulated, so that they don't start chopping up proteins willy-nilly. The "protecting groups" for proteases are in place at the beginning, during their production. Proteases are built as inactive forms known as zymogens, and in order to reveal the active protease, there's a little sliver of protein (called a peptide) that's got to get lopped off.
the ref: Nature 1999, 402, 373-376.
That isn't the only mechanism for regulating proteolysis. You can imagine that if a protease somehow gets activated at the wrong time, or in an out-of-control way, there would be dire consequences (ie, too much protease activity could contribute to stroke or alzheimer's).
When that happens, one natural defense mechanism is the serpin class of proteins. Serpins permanantly (covalently) inhibit proteases, mostly the serine type.

Incidentally, this is the most chemistry I've ever seen in an issue of Nature. Besides the Baran paper and the intro to it by Porco, there's a great piece by Bergman on C-H activation and a review by Toste. Plus, there's an article about chemistry in the NatureJobs section.
UPDATE 3/24: I should've realized Nature did that to coincide with the ACS national meeting.

Will DOI cure what ails me?

As I mentioned on my last post, I've been busy reformatting tons of references, adapting something I've written before to satisfy a slightly different format.
Non-scientists, non-scholarly types: It's like writing that 8th grade term paper all over again, times 100. You know, the one where each of your sources for your bibliography had to be on a separate index card, and you had to get your mom to drive you to the Hackettstown Library to search (are you ready now?) the Readers' Guide to Periodical Literature for information on The Manhattan Project. I can't remember why I chose to write a term paper about the A-bomb at the tender age of 14, but a lot of what I read about for that paper still comes up.
But I digress.
The point is that reformatting references is unbelievably mundane work.
There is some computer software out there that's meant to take care of all that for you. The one I had started using is called EndNote. Endnote interfaces with Word, and it's smart enough to know that when you move text around, the numbers of your references will change if the order's been changed. It has templates for bibliographies in many different journals and can (supposedly) instantly reformat your references to a new journal.
Endnote didn't work well for me at all. I was working with a library of a couple hundred references for this review paper back in 2005. Unfortunately, I couldn't figure out a way to make the software format my references according to the specifications of the particular journal. So, once I was sure I was done shuffling text around, I switched my references to text-only and reformatted them manually, and now I'm reformatting once again.
Is there other, better software out there?
The biggest difference between now and when I was in eighth grade is the ease of access to the internet. One of the handiest technologies for keeping track of the scholarly literature is The Digital Object Identifier System, or DOI. DOI is like a homing device for a journal article, so that no matter where the content moves on the web, looking it up using a DOI locates it and retrieves it.
Recently, some Elsevier journals changed their web and old links no longer worked. If I'd set those links to the DOI of the journal article, they'd still be intact. That reminds me; I need to change my research group's "Publications" page so that everything is indexed by DOI.
What I'm wondering is whether there will come a point where DOI will become the universal reference citation standard, including in print. If that happened, I'd never have to worry about whether I should be using bold or italic font, or whether the authors' surnames come first or last, ever again. Just a simple URL would be all I'd need. However, part of me thinks that if journals (or is it the ACS Style Guidepeople?) were ever going to adopt uniform, URL-based standards, they would have done it a few years ago, at the relative "dawn" of the internet age.
What are the barriers to this, if any? Is it a content searching issue?
If you were going to pick a universal reference style, what would it be and why?

If I were going to Chicago...

If I were going to Chicago, I'd probably be inspired to post something a little more imaginative.
I've been working on a research proposal (read: reformatting references) all week. My brain hurts.

It won't surprise anyone who knows me that I'd want to attend talks that walk the chemistry-biology tightrope. (Read: Jon Clardy, Dale Boger, Laura Kiessling, Sam Gellman, Carolyn Bertozzi, Anna Mapp, Xiaowei Zhuang, etc.)
Here are some of my less obvious go-to talks.

Sunday all day (intermittently): AGFD: Natural Products, Diets and Cancer Prevention. A friend from my last lab always made time to go to the talks from the Ag. and Food chemistry division. I like them, too, because, to me, they have a more "generalist" vibe, and sometimes there are some really interesting chemical structures that they throw up on a slide. You never know where the inspiration for the next target will come from. Not too long ago, there was a postdoc in my group who spent part of his Ph.D. synthesizing a molecule found in Roquefort cheese.

Monday AM: MEDI: Drugs from Academia: Marketed Drugs Discovered in Academic Labs
I'm curious what Bob Holton's going to do with the taxol $$. That, and I have to cheer on Princeton's own Edward C. "Ted" Taylor.

Monday lunch: CHED: Undergraduate Research Poster Session: Organic Chemistry
Mad props to Mike, my little bro, for being the first in the family to present a poster at an ACS meeting. I should probably have gotten more work done.

Monday PM: CHED: Research in Chemical Education
My friend Angie is a teaching postdoc and she's giving a talk about how to keep a lecture hall's worth of sophomores engaged in the organic chem course's subject material. My favorite quote from her teaching experiences is on my Facebook wall. "Sigh....I'm introducing the concept of "backside attack" to 260 college sophomores today. Pray for me." At her postdoc interview she had a week's notice to prepare a lecture on her assigned topic for another ~300 students.

Tuesday AM: PHYS: Xiaowei Zhuang's talk in ACS National Awards in Physical Chemistry
I know I said I wouldn't discuss an obvious one, but I've always really been intrigued by the idea of single molecule imaging studies. I was too afraid of math to take the plunge in a group like that, though. I like to think that one day we'll be able to make movies like this one. I don't think I've linked to that movie yet.

Wednesday AM:
9:55-10:35 ORGN: Biomimetic Natural and Unnatural Products Synthesis
Not a surprise that I'd go here. :)
I think the boss is talking about some new alkaloid-related work, but I'm not sure.

Wednesday PM: INOR: Coordination Chemistry: Characterization and Application
I want to listen to my friends Karl and Eli give talks about their work (or at least, my rudimentary, pop-science understanding of their work, judging by the link).

At some point: run up to Lincoln Park to get breakfast at The Bourgeois Pig, followed by research on, um, surface science at the Bliss Spa, paid for by my imaginary money.

Thursday PM: Nanoparticles: Synthesis, Passivation, Stabilization, and Functionalization
Nanotubes, biosensors, and a talk from someone in Chad Mirkin's group. What's not to like?
Chad Mirkin was here at Princeton a while ago and I regret skipping his talk because of labwork. His science reaches in so many directions.

Note to Anonymous

this started as a reply to a comment on my last post, but it got so long i figured it deserved a post of its own. paul, excuse the lack of caps. i wrote this in the heat of the moment. i know how to diagram sentences, i swear. :)
anonymous,
i do agree with you that for grads busting their asses to pass quals (or get into a good group, or just getting stuff to work for once), the wining and dining days of recruiting are a distant memory. it's definitely true that fewer and fewer upper year students take part in the festivities, and with good reason...
i think that potential chemgrads need to go in well-informed about precisely what you said, and be open to (gasp!) other options. if you really really really want an industry job, they are tough to get these days. maybe the pendulum will swing back, maybe not.
and you're right, a survey can't be comprehensive if everyone isn't polled or doesn't respond, and they're reporting on survey data, so hopefully people trained as scientists know to take it with a grain of salt.
"The 2006 survey involved mailing questionnaires
to a random sample of 24,000
ACS members who were most likely to be
in the domestic workforce. They all resided
in the U.S., were under 70 years of age, and
were not in the emeritus, retired, or student
member categories." -C&EN 9/18/2006
The ACS has over 150,000 members, and it's been discussed at length in the blogs that many chemists don't join ACS at all, or their employers pay for it, so there's some overrepresentation there.
without real poll data, you risk jumping into that nebulous trend story fad. see here and here. so maybe their hands are tied to some extent. i don't think the stories on the survey data should be portrayed as indicative of anything wider. the question is, how could a good poll be properly conducted? with the status of postdocs being different almost everywhere, to cite one example, it would require extensive red-tape wading to reach everyone. on the other hand, since a lot of the job market stuff comes through word of mouth anyway, we could argue about where the best place is to disseminate this information in the first place. federal labor statistics?
i hear about industrial sites that are only hiring one person or two a year, and everybody has a fantastic pedigree. so, what happens to the others? some people are having to take a risk and take a job at a tiny company where they'd really need to stand out to ever be hired by a big guy.there are probably some success stories there, but i don't know as many working chemists as other bloggers. derek's situation is difficult, as well. it's economics driving that, plus perhaps preferring to train someone with less experience in your company's particular way of doing things?
when i got to grad school, i had blinders on. it's partially due to the fact that i went to a small school and didn't know any grad students, and that i had my "eyes on the prize" and didn't stop to think about the fact that i might be good at more than chemistry. my academic work was inextricably linked to my self-esteem back then. i think you can still go to grad school and work in a lab because you like chemistry. that's perfectly OK, but i think that people in this modern economy have to realize that a ph.d. in chemistry can be useful in plenty of different jobs, despite the traditionalists who regard those careers as "alternatives". i struggled with that idea for some time, but i keep hearing about my friends in the grad program that are going to go into consulting or work as a patent agent, two jobs i didn't know existed till grad school. some of them think that they might miss the lab, but maybe not. i even know someone who returned to the lab from an editorial position. it's tough, and you need to work hard to get back into the groove, but it's possible. reading "the world is flat" made me realize that everyone's going to have to work smarter and be creative in order to stay afloat.
the easiest jobs to look at are the ones for which you are supposedly directly trained. med school-> doctor. business school-> executive. law school-> lawyer. sally struthers school->medical assistant, electrician, business management, or accounting. chemistry grad school-> professor or lab chemist? yes, it's true that the other professions don't have the same kind of supply/demand issue in their job markets, but it's not something individuals have much control over, so i went for something different. maybe that's why when i hear about disgruntled grad students first thinking about other professions, those are often the things they gravitate toward at first. it takes real soul-searching to look beyond that. months and months of it, in my case, and if i'm not happy when i start working, i'm not afraid to start the process all over again.
i think the hardest part of the problem is that it's hard to explain this to the young-uns, because they think they have the answers and it won't happen to them, because we have somehow "failed" as chemists. i doubt i would have listened if "future me" went back in time to warn "young, idealistic, slightly cocky me" about such things.

whew. that's a manifesto-length post. speaking of which, if you haven't read milkshake's post, get thee to org prep daily. i learned a lot from it.

My favorite dog and pony show

It's recruiting season at Princeton.
Typically, prospective students don't actually visit our department until they're already admitted, meaning that the department pulls out all the stops to bring in plenty of great people. I was admitted in the first year that Princeton started having a full recruiting weekend, instead of ad hoc visits to the department, and it made a huge difference (we had 1.5 times more people start than what had been common for the past 5 or 6 years). Every department does recruiting differently and presumably tries to do something distinctive/memorable, although I feel like most students come for a certain faculty member or two, not the department as a whole. Back when I was a senior in college, I remember that I had dinner at Yale's Peabody Museum (with the dinosaurs), but I think I heard that that hasn't been done in recent years. True? Also, does anybody know whether MIT still does the lobster bake? I've been told that TSRI does interview its students before admitting them, so the process is a little different there. What are some of the other well-known/ unique/ offbeat recruiting traditions?
The really interesting stuff happens after recruiting, when students commit to the university and then have to join a group. This tends to fuel the gossip for the better part of the fall semester. Who's going where, how many people is so-and-so taking, and the like. The department doesn't allow anyone to officially join a group until the end of November, although many students will start working in their lab of choice the summer before. During the fall semester, all first years attend all the research talks given by the faculty in one of our lecture halls. Unfortunately, as my years here have progressed, I've started to notice that the department's been providing less and less food at these events (we got free lunch and baked goods, the next year it was just baked goods, the year after that nothing at all.) My understanding is that at some places, the research talks are more of an "open house" setup, where interested parties listen to the faculty member discuss what's going on in the group. I've seen some of David Liu's open house posters, for instance. I understand why the department asks everyone to attend every talk, since there have been several occasions where students have switched fields completely at the beginning of grad school, and it's important to know what's going on outside of your field, but I also think that in an open house situation, there's likely to be more lively discussion, because everyone who's attending wants to be there.