Thursday, June 20, 2013

Carbenes: turns out, nature has them, too

Enzymes are like nature's little gloveboxes. It's really quite interesting what kind of chemistries are possible in aqueous, biological conditions just by manipulation of the local electronic and steric environment by the structure of enzymatic active sites.

Take carbenes. Everybody likes a carbene--it's a lone pair on carbon, but it's formally neutral, and it does interesting reactions like alkene insertion (cyclopropanation), C-H insertion, rearrangements, and the like.

One of the more interesting aspects of carbenes is their variable reactivity. They can exist in a singlet (depicted as lone-pair) or triplet (depicted as diradical) form. Depending on their electronic environment, they can react as nucleophiles (aided by a high-lying HOMO) or electrophiles (encouraged by lowering the LUMO). Their reactions can be stereospecific through concerted pathways (singlet carbenes) or non-stereospecific through stepwise mechanisms (triplet carbenes). All of this is tuned, not surprisingly, through the electronic/steric environment around the carbon in question.

Carbenes are typically highly reactive and short-lived, though examples of persistent carbenes are now well-known. N-heterocyclic carbenes (NHCs) make a prime example. The electron-rich di-adamantyl NHC shown above, for instance, was described in 1991 and can be crystallized (it melts, by the way, at 240 degrees Celsius).

Note the electronic nature of the carbene: the carbon is flanked by two nitrogens, each bearing lone pairs capable of donating electron density into the carbene's p orbital. This acts to stabilize the singlet state and imbues NHCs with admirable properties as metal ligands (electron rich sigma donors which bond quite strongly to metal centers) The most famous of these is probably Grubbs' second-generation catalyst, which bears an NHC in lieu of one of the phosphine ligands of the first-generation counterpart. Besides olefin metathesis, though, persistent carbenes (as NHCs) are quite useful ligands for tricky C-C cross-couplings. Specifically, the so-called Pd-PEPPSI complexes are useful for coupling of tetrahedral carbon centers to each other.

It turns out that nature utilizes carbenes as well. Take a look at vitamin B1--also known as thiamin. It's an essential coenzyme which, as it turns out, we can't make and must obtain in our diet. There's several forms consisting of various decorations, usually of the hydroxyl moiety. One of these is thiamin diphosphate (ThDP), which, if you didn't guess, is thiamin with diphosphate attached (it also goes by the name thiamin pyrophosphate, or TPP, which is definitely not confusing at all). ThDP is a coenzyme for pyruvate decarboxylate and pyruvate oxidase, among other enzymes.

If you look at thiamine, there's a place--right between that sulfur and its neighborly nitrogen--that seems like a nice candidate for a carbene. There's been a debate in the literature; that carbon must be deprotonated for catalytic activity, and it hasn't been clear whether the associated enzymatic reaction proceeds via a carbanion or the short-lived carbene. A recent report in Nature Chemical Biology provides evidence for the latter. The authors examined thiamin diphosphate with the enzyme pyruvate oxidase (from bacterial origins). Phosphate was employed as a mimic of the substrate (pyruvate) that would bind similarly but not form a covalent adduct--this was to see if substrate binding might correspond with the formation of a carbene.

Via circular dichroism (CD), and X-ray diffraction, the authors give evidence that although the coenzyme is C-protonated in its resting state, binding of phosphate results in accumulation of either the carbanion/carbene form. This is narrowed down to the carbene chiefly through analysis of the XRD structure. Not only was the electron density consistent, but the bond lengths and angles were similar to synthetic thiazolium carbenes previously reported. The authors mention similar results upon analysis of the ThDP/cyclohexane-1,2-dione hydrolase complex.

Essentially, under physiologically relevant equilibrium conditions, the thiamine/enzyme complex can accumulate a carbene. In water. That's quite cool.

29 comments:

  1. Bà bầu có nên ăn nhiều trứng vịt lộn hay không
    Các mẹ luôn bâng khuân bà bầu có nên ăn trứng vịt lộn không? ba bau nen an gi con thong minh? điều mà các mẹ gặp nhiều khó khăn trong chăm sóc thai nhi. Vâng điều ấy được chúng tôi giải đap qua bài viết sau mời các mẹ cùng tham khảo nhé:
    1 . Trứng vịt lộn và chất dinh dưỡng trong trứng
    Trứng vịt lộn có tác dụng tu âm, dưỡng huyết, ích trí, giúp cơ thể nhanh tăng trưởng. Rau răm có tác dụng trừ hàn, tiêu thực, sáng mắt, sát trùng, mạnh chân gối, ấm bụng, chống đầy bụng khó tiêu...
    Gừng tươi có tác dụng kích thích tiêu hoá, mạnh tim, giải độc thức ăn, chống suy giảm tình dục... Theo quan niệm của y học cổ truyền món trứng vịt lộn ăn cùng gia vị là một bài thuốc, dùng chữa các chứng thiếu máu, suy nhược, còi cọc, đau đầu chóng mặt, yếu sinh lý…
    2. Vậy bà bầu ăn trứng vịt lộn?
    Như chúng ta đã biết trứng vịt lộn chứa nhiều đạm và chất sắt, thực phẩm mát nên các bà bầu khi mang thai có thể ăn được trứng vịt lộn nhưng không nên ăn quá nhiều 1 lúc và thường xuyên. Nên ăn trứng chín và đang còn nóng đặc biệt không nên ăn kèm với rau răm. Không nên ăn trững vào buổi tối vì sẽ gây ứ bung khó tiêu. Tóm lại bà bầu có thể ăn được trứng vịt lộn nhưng không nên ăn quá nhiều nên ăn 1-2 quả trong 1 tuần.
    >> Tìm hiểu thêm: ba bau co duoc an thit cho
    3. Lời khuyên
    Chúng tôi khuyên bạn trong thời kì mang thai nên ăn các chất dinh dưỡng tốt cho thai nhi tránh ăn và uông các chất kích thích, tươi sống. Cần cân bằng đầy đủ các chất dinh dưỡng để thai nhi phát triển tốt nhất!

    ReplyDelete
  2. Businesses need to stay ahead in the game and think ahead of the competition which is precisely what the experts at the SEO company do. click here to investigate

    ReplyDelete
  3. Great Blog! You should consider writing about a no gmat emba! I feel like so many more people would be less scared and daunted and more likely to check out a healthcare executive mba when they think they have less constraints.

    ReplyDelete
  4. Bạn đang kiếm nguồn sản phẩm để kinh doanh ? Vậy ở đâu để kiếm nguôn đây ?

    => http://chatuchak.vn Nguồn nhập sỉ sản phẩm THái lan đầu tiên tại việt Nam


    => Vận chuyển hàng thái lan : pusa.asia/van-chuyen-hang-thai-lan-viet-nam/

    ReplyDelete
  5. Here is the best college to study BSc Medical Imaging Technology in Bangalore. If you are looking to any colleges for above mentioned subject in Bangalore, then visit the following link. BSc Medical Imaging Technology Colleges In Bangalore

    ReplyDelete
  6. I'm very Glad to visit your informational Post. THC Vape Packaging Packaging boxes are really necessary for any kind of product. If you want to pack your products in a stylish way then use these THC Vape Packaging with customized designs, styles, colors, shapes, and stocks. We are also offering error-free designing and free shipping services all over the USA.

    ReplyDelete
  7. your blog post having lots of information according to my need. dank vape packaging is very necessary for your vape products and it makes your product attractive and effective and it also helps to increase our product retail market

    ReplyDelete
  8. I'm very Glad to visit your informational Post. Thc Vape Packaging Packaging boxes are really necessary for any kind of product. If you want to pack your products in a stylish way then use these Thc Vape Packaging with customized designs, styles, colors, shapes, and stocks. We are also offering error-free design and free shipping services all over the USA.

    ReplyDelete
  9. After Governor Rauner vetoed 15ng/ml and suggested 5ng/ml, we on the Traffic Laws and Courts Section Council for the ISBA, voted to oppose the change because it had been not based in science and was basically an arbitrary number that was assigned that would still CONVICT SOBER DRIVERS.
    krt carts

    ReplyDelete
  10. This article will outline all the different strategies you should be aware of when it comes to soccer.

    Top IAS Coachin in Mumbai

    ReplyDelete
  11. Hello Dear,

    I Like Your Blog Very Much. I see Daily Your Blog, is A Very Useful For me.

    You can also Order Afghan Kush UK.,Buy AK47 Online EU, Order AK47 Online UK,Buy Alaskan Thunderfuck EU,Buy Blue Cheese Online,Buy Blue Dream EU,Blueberry Kush for sale Online,cannabis for sale uk,Buy Bruce Banner Online,Buy Bubba Kush EU,Buy Bubble Jack Strain Online,Candyland Marijuana Online,Buy Critical Kush Online Europe

    Visit Now:- https://www.dankrevolutionstore.com/

    WHATSAPP ONLY: +31 684404872
    Email Id:INFO@DANKREVOLUTIONSTORE.COM

    ReplyDelete
  12. Medical marijuana is officially available for purchase at Medicalbudsonline. You do not need to present and register with Medical Marijuana Control Program to obtain your marijuana card

    ReplyDelete
  13. This blog has provided me with a wealth of knowledge, so thank you.

    Ayurvedic Treatment of Weight gain

    ReplyDelete
  14. Buy weed online, For Your Medical And Therapeutic Benefits.

    ReplyDelete
  15. Excellent read, Positive site, where did u come up with the information on this posting? I have read a few of the articles on your website now, and I really like your style. Thanks a million and please keep up the effective work

    (teacup yorkie puppies for sale )
    (yorkie puppies )
    (yorkshire terrier breeders )
    (yorkie puppies for sale )
    (teacup yorkie puppies for sale )
    (yorkshire terrier puppies )
    (teacup puppies near me )
    (yorkies near me)
    (yorkie puppies for adoption )
    (yorkie puppies for adoption )
    (yorkie puppies near me )

    ReplyDelete

  16. Excellent read, Positive site, where did u come up with the information on this posting? I have read a few of the articles on your website now, and I really like your style. Thanks a million and please keep up the effective work

    cane corso puppies for sale
    cane corso breeders near me
    cane corso for sale
    cane corso breeders
    cane corso puppies
    cane corso puppies near me
    cane corso for sale near me
    cane corso puppies for sale near me
    shih tzu puppies for sale

    ReplyDelete
  17. Writers are a unique breed. You know when you're reading content written by an expert, or at least a very intelligent writer. Custom Vape Boxes

    ReplyDelete
  18. Nice Blog , get more information about QuickBooks solution at

    QuickBooks Customer Service

    ReplyDelete
  19. If you want a dog with personality, you may sometimes get a stubborn personality too! These dachshund puppies for salelittle pups are fiercely independent, and that may mean they disagree with you sometimes. However, they truly love affection, so positive and reward-based training styles are best for this breed.
    Due to their keen sense ofsphynx kittens for sale $500 smell, doxie puppies may pick up a whiff of something interesting and have a hard time focusing. During puppyhood, these dogs thrive in socialization classes.
    Poodles are regarded as one of the most intelligent breeds in the world. They’re highly trainable and well suited for just about any task you put them to — and you will want to give them tasks to do. Bored Poodles can get destructive if they aren’t physically and mentally stimulated. But active owners who can toy poodle for salemeet their dog’s needs will find a loving, smart, trainable, and loyal family companion.

    See below for complete list of dog breed traits and facts about Poodles!
    Poodles are highly trainable and pick up skills quickly. They love positive reinforcement and mini dachshund puppies for saleexcel in tracking, agility, and obedience. Poodle puppies benefit from socialization classes to build good puppy behavior.https://www.poodlespring.com/ Poodles are especially aware of the tone of your voice, so if you need to reprimand your poodle, be firm, but not harsh.
    Energy Levelpoodle puppies for sale Poodles (of every size) are active dogs that need exercise on a daily basis. Have a pool? They love swimming as a great way to burn that dog fuel. Playing multiple games of fetch and retrieval helps to bond with your poodle and tucker them out.

    ReplyDelete
  20. https://skybudshops.com/product/buy-dank-vapes-online/

    ReplyDelete