Acetyl Fentanyl: Dangerous, Poorly-Named Street Drug
Aug30

Acetyl Fentanyl: Dangerous, Poorly-Named Street Drug

The U.S. Centers for Disease Control and Prevention has released a summary on a cluster of 14 deaths in Rhode Island earlier this year attributed to "acetyl fentanyl," an analog of the potent, short-lived opioid used in pain management and outpatient anesthesia. The report, "Notes from the Field: Acetyl Fentanyl Overdose Fatalities — Rhode Island, March–May 2013," appears in the August 30, 2013 issue of Morbidity and Mortality Weekly Report (MMWR). The first 10 deaths were reported in the Providence Journal on May 13, 2013, leading CDC officials to join the team in the investigation. A total of 14 deaths were identified. Samples from the decedents gave positive ELISA results for fentanyl but GC/MS revealed an analog that authorities are calling acetyl fentanyl. A CDC health advisory released in June briefly details the chromatographic pattern and mass spectra. Cayman Chemical Company, who offers the reference material, also calls it acetyl fentanyl, but offers desmethyl fentanyl as an alternative. The IUPAC name is N-​phenyl-​N-​[1-​(2-​phenylethyl)-​4-​piperidinyl]-​acetamide; fentanyl has a propionamide instead of the acetamide. A CBC news story described a late April series of drug busts in Montreal that included seizure of a compound they called desmethyl fentanyl. The current MMWR release also links to an alert from the Pennsylvania Department of Drug and Alcohol Problems that reports 50 acetyl fentanyl deaths in the state this year, through June 27th (PDF). Most curious is that the compound has not been described before as a recreational drug. It's not available as a prescription drug anywhere in the world and is only a minor side product (0.04%) found in prescription fentanyl (DOI: 10.1016/j.jpba.2010.04.004). In a lengthy discussion on Twitter last night and this morning with Chemjobber, SeeArrOh, and others, I initially asked whether acetic anhydride could have been used to acetylate fentanyl, thinking -- without looking at the structure -- that it was truly acetylated. I found later that fentanyl is made from 4-anilino-N-phenethylpiperidine (ANPP) using either propionyl chloride or propionic anhydride. Hence, acetyl fentanyl could be made by reacting ANPP with either acetyl chloride or acetic anhydride (That's the extent of my synthetic expertise, Dear Reader.). The major problem with acetyl fentanyl -- or fentanyl for that matter -- is its high potency relative to natural opioids like morphine or the more potent synthetic, heroin. As a result, the CDC recommends that emergency rooms and other facilities providing substance misuse care services stock up on the opiate receptor antagonist naloxone in anticipation of an increase in overdoses across North America. But it looks like we're stuck with acetyl fentanyl as the name. Any...

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Does Ada Yonath’s Gender Really Matter?
Jul31

Does Ada Yonath’s Gender Really Matter?

  My apologies to regular readers and my colleagues at C&EN for my month-long silence at the blog. I saw cobwebs on my laptop screen when I opened the back end this morning. Part of my hiatus came from complications of an infected molar extraction and my inability to concentrate. I've also been trying to take short Internet holidays over the last two months because all of the political nonsense in my state is negatively affecting my mental health. But the tooth canyon is about 50% healed and our state legislature has finished, for now, shifting progressive North Carolina toward its pre-Research Triangle Park level of ignorance, racism, and poverty. During this month, I came across an excellent post on the Scientific American Guest Blog by Atlanta-based science journalist, Kathleen Raven. In "Ada Yonath and the Female Question," Raven discusses her experience at this year's Lindau Nobel Laureate meeting -- dedicated to chemistry -- and her reflections on hearing and attempting to interview the 2009 Nobelist in chemistry, Dr. Ada Yonath. Yonath, a structural chemist recognized for her extensive work in showing how the ribosome catalyzes protein synthesis, has generally not made much of the fact that she's only the fourth woman to receive the Nobel Prize in Chemistry, and the first since Dorothy Hodgkin in 1964. As I did back in 2009 when interviewing Yonath at the North Carolina Biotechnology Center, Raven debates whether focusing on Yonath as a female scientist is a good thing for the cause of women scientists. Should we focus only on the accomplishments? Or should we focus on her accomplishments in the context of the distinct barriers often facing women scientists? I'm equally torn, particularly since my 20-year laboratory career was advanced by a group that consistently ranged from 75% to 100% women. I never specifically recruited women to my laboratory but it seems that they might have self-selected for reasons not known to me. My activism in diversity in science extends back to my pharmacy faculty days at the University of Colorado where I assisted in selecting minority scholarship recipients for a generous program we had from the Skaggs Family Foundation. The goings-on in North Carolina politics is not germane to this scientific discussion. We can speak all we want about our modern society being post-racial and having more women leaders than ever. But voter laws that disproportionately disenfranchise African-Americans and legislation that severely compromises women's reproductive health tells me that we still need to pay attention to the influence of racial and gender attitudes. Heck, even our Governor Pat McCrory showed his true colors yesterday while protestors, primarily women, were holding a...

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Country of Discovery Periodic Table of the Elements
Jun24

Country of Discovery Periodic Table of the Elements

Admit it. You have a Periodic Table of the Elements shower curtain. Don't you? Dmitri Mendeleev (and Julius Lothar Meyer, 1870) might have never predicted that his 1869 scientific tool would give rise not only to consumer products for the chemistry enthusiast but also a graphic visual adopted for all manner of non-scientific purposes: The Periodic Table of Beer Styles The Periodic Table of Drupal Modules The Periodic Table of Typefaces The Periodic Table of Islam ...and, for balance, The Periodic Table of Atheists and Antitheists (yes, please add your own favorites in the comments below) Well, my morning coffee Twitter feed brought me a new version that's 1) about actual chemistry and 2) useful for educational purposes. A story in this week's Smithsonian.com Smart News displays the periodic table of the country of element discovery as constructed by Glaswegian chemistry PhD student, science communicator and dancer, Jaime B Gallagher (Twitter @JamieBGall). I'm reminded that the stories behind each element not only tell us history, but also how early chemists differentiated between the elements. While Gallagher tries to give credit to multiple countries for some of the discoveries, debate will undoubtedly ensue. This is is good thing. It'll get folks talking about chemistry. Lithium, for example, was discovered by Swedish chemist Johan Arfwedson who liberated it from petalite ore, discovered by Brazilian Jose Bonifacio de Andrade de Silva while visiting the Swedish countryside. Swede Jans Jacob Berzelius named it lithos (for stone - think lithotrypsy). But it wasn't isolated until the independent work of Sir Humphrey Davy in England and William Brande in Sweden. So while Gallagher is probably right to fully credit Sweden for lithium, one could make an argument that the UK flag should partially be at position 3. The story might also get us talking about modern uses of the elements. For example, a large deposit of lithium has just been discovered in Wyoming, a find that's likely to put the States in a better spot as international demand for lithium grows rapidly. And while chest-thumping U.S. citizens might want to boast international superiority, we're only tied for third (or fourth...with France!) for the discovery of 17 elements. The UK is tops with 23 followed by Sweden and Germany with 19 each. Have fun looking at this table and consider using it in your science and public education efforts. There's something here for everyone. And before my graphic designer relatives chime in, yes, Jaime should have enlisted the help of a professional illustrator for color and typeface choices. But, hey, he's already done the content legwork.  ...

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Daughters and Famous Women Chemists
Jun04

Daughters and Famous Women Chemists

Earlier last month, you may have seen a beautiful set of images by Austin-based wedding and lifestyle photographer Jaime C. Moore. To celebrate the 5th birthday of her daughter Emma, Moore wrote: Set aside the Barbie dolls and Disney princesses for just a moment and let's show our girls the real women they can be. Moore then had Emma do some five-year-old dressing and posing, but in character of some major female role models throughout history: Susan B. Anthony, Amelia Earhardt, Coco Chanel, Helen Keller, and Jane Goodall. (Commenters politely focused on Chanel's business acumen and not her less savory political associations.) Moore's photography is beautiful (and we may have to go down to Austin for a new series of family photos ourselves) and she captures all the promise and aspirations a five-year-old girl might have to do something other than be a helpless damsel-in-distress in psychotherapy because of a cruel and manipulative stepmother. With our PharmKid approaching 11, we still maintain a large house collection of costumes and various get-ups that began with Disney princesses and has now progressed to characters she and her friends concoct (now writing screenplays to accompany their stories while Dad is drafted for filming purposes). But I wish that we had instead been overrun with role-playing costumes for our daughter to emulate women of strong character and high intellect. So I got to thinking: Why don't we have costumes for our girls to dress up as famous women scientists, especially female chemists? And with all due respect to Marie Curie and Irene Joilot-Curie, perhaps we might find more contemporary characters for our daughters. For me, as a North Carolinian and cancer pharmacologist, the chemist character I'd most love to see around here is the late Nobel laureate and Burroughs-Wellcome chemist, Gertrude (Trudy) Elion - in a single, striking royal blue gown. But here, even I fall into the trap of thinking of a deceased character. How about Ada Yonath, ribosome structural chemist and 2009 Nobel laureate in chemistry? Therefore, I turn to you, Dear Reader. If we were to, say, launch a Kickstarter campaign for the manufacture of famous women costume sets for young girls, who of today's women chemists would be ones you'd like to see your daughter personify?...

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The Cinnamon Challenge: On Being Charged with #Chemophobia
Apr23

The Cinnamon Challenge: On Being Charged with #Chemophobia

As many of you are likely to have heard yesterday, a paper from Steven Lipshultz, MD, at the University of Miami appeared in the journal Pediatrics detailing poison control center reports on an adolescent misadventure called The Cinnamon Challenge. The challenge: to swallow a teaspoon of cinnamon powder in 60 seconds without any liquids. The practice has been rummaging about the internet since 2001 but really took off on YouTube over the last three years. Lipshultz's report discusses the risks of such tomfoolery, particularly due to the inhalation of cinnamon powder while one is choking. I planned to write about this practice both here and at my Forbes.com blog since I thought both chemists and the general public would be interested in the topic. I wrote the Forbes post earlier this morning and drew a series of comments from a kindly San Diego-area chemist who took issue with my facetious comparison of cinnamaldehyde (cinnamic aldehyde) to formaldehyde. While Lipshultz states that much of the acute pulmonary toxicity of cinnamon powder is likely due to the cellulose content, I submit that some damage could be due to protein adducts formed by cinnamaldehyde. Yes, yes, it's not as dangerous as formaldehyde. But even at roughly 1% (w/w) in the powder, I hypothesize that the cinnamaldehyde could cause epithelial damage. Also note that cinnamaldehyde is not just any aldehyde but rather an unsaturated aldehyde. That makes me think of acrolein. The experiments have not been done. But one animal study has been published showing that intratracheal administration of cinnamon powder -- not pure cinnamaldehyde -- can cause acute lung injury in rats and trigger pulmonary fibrosis within a month. Alas, my concerns about cinnamaldehyde rubbed two commenters the wrong way and one, well, sought to chemsplain me. I was originally trained in toxicology so I know the whole Paracelsan story that the dose makes the poison (to which I'd also add "route of administration"). But do you chemists, especially those in chemical toxicology, think that I'm overreacting (as it were) to the potentially reactive nature of cinnamaldehyde in inhaled cinnamon powder? I'm willing to be corrected if I appear to suffer from #chemophobia. But I hypothesize that 1% (w/w) cinnamaldehyde can be...

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