Another World - Martin Villiger - Antarctica (CD)

Reactions of allyl bromide under the Luche conditions with g-aldo esters afforded ghydroxy esters, which were converted in a one-pot reaction to g-allyl-g-butyrolactones Scheme 22 []. Formation of g-allyl-g-butyrolactones from g-aldo esters Hannessian and co-workers recently reported the allylation of N-protected aamino aldehydes as an efficient route to Phe-Phe hydroxyethylene dipeptide isostere utilized for the design of potential inhibitors of renin and HIV-protease [].

This reaction was extended to various allyl halides to give anti-b-amino alcohols in high yields. Alternatively, enantiopure syn-b-amino alcohols were obtained in good yields after Swern oxidation and reduction with NaBH4 []. They showed that the diastereoselectivity in fact depends on the nature of the metal and of the halide indicating that different mechanisms can operate in these Barbier-type reactions [97].

Related to these reactions are the zinc-promoted allylation reactions of oximes. Thus, enantiomerically pure or highly enriched allyglycine and its chainsubstituted analogs are easily accessible from the reaction of the sultam derivative of benzyl glyoxylic acid oxime with allylic bromides in aqueous ammonium chloride Scheme 23 [].

Allylation of sultam derivatives 5. Thus, strongly acidic conditions HBr, AcOH were required to perform the heterogeneous reaction using metallic tin, allylic bromides and aldehydes, even if the presence of water accelerated the reaction compared to the reaction in pure diethyl ether.

Allylation of ketones required metallic aluminum as an additive []. In this way, five- or six-membered rings were prepared through intramolecular reactions Scheme 24 []. Water as Solvent in Organic Synthesis 23 Scheme When the aldehyde contained a free hydroxyl group, then the reaction under sonication became very rapid and efficient [].

When applied to carbohydrates, this sono-allylation proceeded with high threo selectivity and allowed the preparation of higher-carbon complex sugars directly in aqueous ethanol without protection Scheme 25 []. In this case also sonication can be replaced by heating the reaction mixture for 2 h under reflux [].

Highly threo-selective tin-mediated allylation of sugars Active zero-valent tin can also be generated by reduction of tin II chloride by aluminum in aqueous THF. In this way, cinnamyl chloride gave high anti diastereoselectivity in the reaction with aldehydes [].

In fact, under acidic conditions, tin II halide can be used directly without concomitant reduction. Thus, starting from E -rich 1-bromobutene, the SnCl2-mediated allylation of aldehydes yielded homoallylic alcohols mainly with anti configuration.

Curiously, syn allylation occured with tin II iodide, suggesting in this case an acyclic antiperiplanar transition state even more favored by the addition of tetrabutylammonium bromide which prevents the tin atom from coordinating the oxygen atom of the aldehyde []. Homoallylic alcohols have also been prepared in good yields with various allyl chlorides and aldehydes in the presence of SnCl2 and KI. The reaction can be applied to aliphatic aldehydes, conjugated enals and keto aldehydes [].

The SnCl2-mediated allylation of carbonyl compounds is even possible with allylic alcohol or its corresponding methylcarbonate in the presence of palladium catalyst Scheme 26 []. In the reaction of E -butenol with benzaldehyde in the presence of SnCl2, the rate and the anti selectivity were shown to increase with the amount of water in the reaction mixture [].

Propargylation and allenylation products are formed without marked selectivity []. This reaction is also possible using SnCl2 with KI. Whereas the reaction with benzaldehyde gave only the propargylation product, in this case, aliphatic aldehydes gave rise to a mixture of propargylation and allenylation products in a 70 : 30 ratio [].

All these reactions can be carried out with preformed organotin IV compounds. Thus, allyldibutyltin chloride or allylbutyltin dichloride reacts with aldehydes or ketones in high yields to give the corresponding homoallylic alcohols []. However, tetraallyltin requires acidic conditions and reacts exclusively with aldehydes [].

Recently, the Sc OTf 3-catalyzed allylation of aldehydes with tetraallyltin was shown to proceed smoothly in micellar systems to afford the corresponding homoallylic alcohols in high yields without any organic solvent []. In a related reaction, aqueous allylation of imines has been reported by Belluci and co-workers using allyltributylstannane under lanthanide triflate catalysis [].

Alternatively, the reaction can be performed without catalysis directly with the formaldehyde-generated immonium salts in aqueous media to give, in excellent yields, bis-homoallylamines and tertiary homoallylamines with primary and secondary amines, respectively [].

These homoallylic amines were also prepared by Sc OTf 3-catalyzed three-component reactions of aldehydes, amines and allyltributylstannane in micellar systems []. Compared to other metals, indium is resistant to oxidation, hydrolysis, and has a very low first ionization potential 5. In , Li and co-workers reported the first allylation of aldehydes and ketones mediated by indium in water without any additives or special activation [].

In particular, the use of indium allowed reactions with acid-sensitive compounds [] or the preparation of complex carbohydrates such as deaminated Water as Solvent in Organic Synthesis 25 Scheme Synthesis of a N-acetyl neuraminic acid derivative sialic acids KDN [] using a-bromomethylacrylate and mannose or N-acetylneuraminic acid with the same halide and N-acetyl mannosamine Scheme 27 []. Several analogs of sialic acids have been prepared in this way [], including a phosphonate analog [].

Compared with tin, indium-mediated reactions with pentoses and hexoses give uniformly higher yields and higher threo selectivity as a result of a chelation-controlled reaction. This led, as shown in Scheme 28, to a rapid synthesis of 3-deoxy-Dmannooctulosonic acid KDO []. Zero-valent indium can also be generated in situ by reduction of indium III halide with metallic zinc or aluminum [] or even tin []. The regio- and diastereoselectivity of the reaction using g-substituted allyl bromides with aldehydes was carefully investigated by Chan and Isaac [].

The reaction was as expected g-regioselective except when the g-substituent was too bulky i. Synthesis of KDO through erythro-selective allylation of a carbohydrate acetonide 26 A.

In contrast, as shown with the reaction with sugars, the indium-mediated reactions with a-oxyaldehyde is generally highly syn stereoselective as a consequence of chelated intermediates. In a recent study by Isaac and Paquette, high levels of the 3,4-syn;4,5-anti diastereoisomers were produced in the indium-promoted additions of Z bromomethyl-2butenoate to several a-oxy aldehydes. This stereodifferentiation has been attributed to the strong geometric bias exercised by the allylindium reagent and adherence to a Felkin-Ahn transition state alignment Scheme 29 [96].

Diastereoselection in the allylation of a-oxy aldehydes However, additions of an allylindium reagent to a-thia aldehydes are minimally diastereoselective indicating that the allylindium reagent is not thiophilic. In contrast, as seen in the case of the reaction on N-acetyl mannosamine for the preparation of sialic acid vide supra , substituted a-amino aldehydes with a not too bulky amino-protecting group, give rise to high levels of diastereoselection resulting from chelation control []. The aqueous indium-mediated Barbier reaction can also proceed intramolecularly to give five-, six- and seven-membered rings which can be further cyclized to cis-fused a-methylene-g-lactones [].

A useful methodology of carbocycle enlargement by one [] or two carbon atoms [] has recently been reported using intramolecular indium-mediated allylation of 1,3-dicarbonyl compounds Scheme Several other interesting synthetic procedures have recently been reported.

Thus, b,g-unsaturated ketones were synthesized from aqueous allylation of acyloyl pyrazoles, whereas tertiary alcohols were obtained with acyloyl imidazoles []. A variety of b-hydroxy esters were prepared efficiently by indium-mediated allylation of aldehydes using 3-bromochloropropene followed by ozonolysis [].

Highly functionalized b-lactams were prepared by allylation of 2,3-azetinediones []. Water as Solvent in Organic Synthesis 27 Scheme One and two carbon atom ring enlargements More unexpected was the formation of cyclopropane during the indiummediated reaction of dibenzylidene acetone with allyl bromide which gave 1,1-distyryl butenyl cyclopropane as a mixture of four isotopomers Scheme 31 [].

In a related reaction, a simple and efficient one-pot method was developed to give chiral homoallylic amines and amino acids from the respective aldehydes with high stereoselectivity [].

Formation of cyclopropane during allylation of dibenzylidene acetone 5. Similarly, the same reaction can be promoted with metallic lead [], highly reactive antimony prepared by the NaBH4 reduction of SbCl3 [] or a mixture of manganese and catalytic copper []. In the latter case, aromatic aldehydes reacted whereas ali- 28 A. When copper was omitted, the reaction of aromatic aldehydes in the presence of a catalytic amount of acetic acid led to the corresponding pinacol-coupling product in fair yields.

Tetraallylgermane pointed out as less toxic than tetraallyltin was also shown to react with carbonyl compounds, preferably with aldehydes, under scandium III triflate catalysis in aqueous nitromethane in which the presence of water was shown to be essential []. Sonication enhanced the efficiency of the process leading to the 1,4adducts in very good yields []. This reaction was later extended to various a,b-unsaturated compounds such as esters, amides and nitriles [].

This reaction which is promoted under pressure [] is accelerated in water due to the hydrophobic effect as already postulated see Sect. In fact, various 1,3-diketones, such as 1,3-cyclopentadione, have been shown to add readily to a,b-unsaturated ketones in good yields without any catalyst Scheme 32 []. However, during the addition of b-keto esters onto enals, ytterbium triflate proved to be an efficient catalyst [] as in the Michael additions of a-nitro esters [].

Several water-soluble phosphines gave the corresponding phosphonium salts in good yields when added to a,b-unsaturated acids [] or activated alkynes []. With alkynes, vinyl phosphine oxides or alkenes were formed depending on the pH of the aqueous solution. Significantly, the reaction of nitroalkanes with butenone is considerably accelerated when going from Scheme Michael addition of nitromethane onto methyl vinyl ketone non-polar solvents or polar solvents such as methanol to water.

This uncatalyzed reaction, considered impossible, proceeded smoothly without added base in a completely neutral medium Scheme 33 []. Noteworthy was the increase of the selectivity in water toward the adduct when using nitromethane. Under slightly alkaline conditions, cetyltrimethylammonium chloride was shown to catalyze the addition of various nitroalkanes onto conjugated enones [].

Amines also reacted in aqueous Michael additions, especially with a,b-unsaturated nitriles []. The lack of apparent reactivity of a,b-unsaturated esters comes from the reverse reaction which is particularly accelerated in water. In these amine additions, water activation was compared with high pressure giving support to the implication of the hydrophobic effect.

A related reaction is the Baylis—Hillman reaction which proceeds readily in water with a good rate enhancement Scheme 34 []. Baylis—Hillman reaction 5.

The reaction involves activated carbonyl compounds enol, enolates, various enol ethers which add on another carbonyl compound or various electrophiles in related reactions.

As most of the activated compounds are compatible with water, it is not surprising that the aldolization in aqueous conditions became an efficient process in view of the negative activation volume of the reaction. The diastereoselectivity depends greatly on the reaction conditions. Thus, in a intramolecular aqueous aldolization, the acid-induced reaction of a keto aldehyde provided a syn hydroxy ketone while the base-catalyzed reaction led to the anti isomer Scheme 35 []. Similarly, the water-soluble unprotected sugars can be extended by one carbon atom by reaction with formaldehyde Scheme 36 [].

One carbon atom extension of ketose The aqueous conditions also allowed the use of anionic or cationic surfactants which led in excellent yields to the dehydrated condensation products, making this methodology an attractive route for a one-pot synthesis of flavonols Scheme 37 []. Preparation of flavonols through aqueous aldolization The Mukaiyama reaction is the reaction between a silyl enol ether and an aldehyde in CH2Cl2 in the presence of a stoichiometric amount of TiCl4 [].

The reaction is generally highly diastereoselective and leads to the anti diastereoisomer in the case of the trimethylsilyl enol ether of cyclohexanone with benzaldehyde. The same reaction in the same solvent proceeded without catalyst but under high pressure 10, atm to give the reverse diastereoselectivity now in favor of the syn isomer []. As expected, this reaction between two small hydrophobic molecules with a large negative activation volume must be accelerated in water compared to an organic solvent.

In fact this 31 Water as Solvent in Organic Synthesis solvent temp. The Mukaiyama reaction under various conditions reaction does not work in any organic solvent without an acidic catalyst or without pressure.

Taking into account the competitive hydrolysis of the silyl enol ether, this reaction is remarkable. The method was shown to be general and was extended to a variety of aldehydes and several a,b-unsaturated carbonyl compounds giving uniformly 1,4-addition with aldehydes and a mixture of 1,4- and 1,2adducts in the case of ketones [].

Later, this aqueous version of the Mukaiyama reaction was shown to give near quantitative yields in the presence of a water-tolerant Lewis acid such as ytterbium triflate []. Keeping with the same concept, copper II triflate [], indium III trichloride [], tris pentafluorophenyl boron [] and scandium III triflate in the presence of a surfactant [] have proved to be active catalysts.

Related to the aldolization reaction is the Mannich reaction, which proceeds readily in water []. Allylsilanes [] and allylstannanes [] were also shown to add to iminium salts under Mannich-like conditions. The Henry reaction which can be performed in an aqueous medium has been made more efficient in the presence of surfactants. Of interest also is the aqueous Reformatsky cross-coupling reaction between a-halo ketones or aldehydes and carbonyl compounds in the presence of zinc, tin and indium.

Like the Barbier-type reactions, indium was found to be the most efficient metal and it strongly reduced undesirable side reactions such as the reduction of the halide []. As usual in aqueous reactions implicating carbonyl compounds, lanthanum III triflate promoted the reaction [].

Many efforts have also been made using the inexpensive, but not very reactive, H2O2 which must be used most of the time with additives. We will focus here on the reactions that have a special outcome due to the use of water compared to the usual solvents.

Although the reaction proceeds under heterogeneous conditions, the reaction is often more efficient than in organic solvents and is suitable for acid-sensitive alkenes. In pure water, with water-soluble alkenes, the 1,2-diols are generally obtained with a high degree of trans selectivity []. Electron-poor olefins, such as a,b-unsaturated acids, react slowly under these conditions, but the corresponding epoxy acids can be obtained in good yields using H2O2 in the presence of sodium tungstate [].

Oxidation of alkenes with H2O2 is quite general providing that a co-additive is present. Thus, good results were obtained with diphenylphosphinic anhydride []. In the case of a,b-unsaturated ketones, epoxidation was performed in good yields using sodium perborates in slightly alkaline aqueous conditions []. The regio- and stereoselectivity of the epoxidations of polyolefinic alcohols are generally low in organic solvents.

In contrast, the reaction in water using hydroperoxide in the presence of a transition metal proceeds with good regioand stereoselectivity []. Likewise, the reaction with monoperoxyphthalic acid MPPA is also regioselective when the pH of the reaction mixture is controlled []. In a similar way, MPPA epoxidizes allylic and homoallylic alcohols in strongly alkaline aqueous medium, with high diastereoselectivity in cycloalkenols in favor of the syn adducts except for 2-cycloheptenol which gives the trans isomer as the major compound [].

The inexpensive and easy to handle sodium percarbonate in aqueous THF allowed the conversion of various hydroxylated benzaldehydes or acetophenones to the corresponding hydroxy phenols through the so-called Dakin reaction. Baeyer-Villiger oxidations of ketones using MCPBA in water were very fast and efficient and afforded the corresponding esters or lactones in very good yields. At room temperature no hydrolysis occurred [].

Water as Solvent in Organic Synthesis 33 Selective oxidation of methyl groups can be achieved by platinum salts in aqueous solution. Likewise the methyl group of ethanol can be oxidized without affecting the hydroxyl group []. Ethylbenzenes yielded acetophenones []. However, the use of water could bring not only the usual advantages of low cost, security and easy isolation of the products e. For example, the regioselectivity in the reduction of alkadienoic acid which was performed by hydrogen in the presence of RhCl[P p-tolyl 3]3, is largely dependent on the solvent [].

Chiral water-soluble catalysts have been prepared for asymmetric hydrogenation of 2-acetamidoacrylates. Alternatively, water-soluble bis diphenylphosphino pyrrolidines were shown to give higher enantiomeric excesses []. Although water was found to generally decrease the enantioselectivity in the use of chiral sulfonated diphosphines [], the presence of amphiphiles in the reaction mixture enhanced significantly both the reactivity and the enantioselectivity of the reduction [].

In this way, good yields were obtained in the selective reduction of the double bond. Medium sized frame. Mavic aksium race wheels. Bladed spokes. New chain. Carbon seatpost Easton ea50 bars. Race face cadence hollowtech crankset. External bearing bottom bracket. New bontrager race x lite hardcase tires. This bikes is in almost new condition. Very low miles, I cannot find any dents, cracks, chips or scratches. It looks great, and has been just tuned up by professional mechanics. This is perfect for anyone looking to get a quality full carbon racing bike for the upcoming season.

It is very light and very fast. Cranks, and brakes. Dura Ace rear derailleur. Heel rub, chain, etc. Carbon Steerer, Cannondale S. Bike will be professionally packed and shipped and includes shipping insurance. See my other listings for more great outdoor clothing and gear! Check out our store at. We are an outdoor gear consignment store in Fort Collins.

Local pickups welcome! Trek 6. Hi Guys here I have is a one of a kind Trek Madone 6. This bike is drop dead gorgeous and the build will be completed when the auction has ended by that time A stunning bike to ride and to look at.

The frame has been custom sprayed with Lamborghini orange and black, there are some gold flakes in the orange so in the sun it shines a little. The bike will come with handlebar tape, chain and a saddle soon, possibly a Prologo saddle.

The build is: Full Shimano Ultegra groupset FSA carbon handlebars 44cm wide. Dura Ace tubular wheelset These wheels will require carbon brake pads.

Vittoria Corsa Evo tubular tyres. It has done very little miles and the bike shows it. A perfect opportunity to grab a bike which cannot be found anywhere else in the world. Built and serviced by a mechanic and if you would like to change any parts I am more than willing to do so. Whether you're looking to give cyclocross a try. For sale is a Motobecane Fantom Pro Cross. The frame is 56cm. And is made of aluminum. The fork is carbon fiber.

This bike is in excelllent condition considering that it is in fact a used cross bike. It was primarily used for riding on gravel roads and when the weather was nasty. It has been well maintained- the bottom bracket and drivetrain are in good condition and ready for you to put on many more miles. The frame is worn in places, but the clear coated aluminum looks great. Front Derailleur: Shimano Ultegra.

Rear Derailleur: Shimano Ultegra. Please feel free to ask me any questions. Thanks for bidding and good luck! I have this listed as used. But this is basically a new bike. The following is a list of parts and their condition-Please note most parts are new or slightly used.

For the right offer. And a small cut on the hood. I also have an Orbea Carbon Pro Selle Italia SLR. And is ready for any level of riding! If you live in Alaska. But no International bidding or shipping. Deda stem. Carbon saddle. There are only very minor paint chips pic 6 that have been touched up so its almost invisible. Bike has less than miles. Bike is listed for local sale. If you are in chicago or champaign area. Can come check the bikes out. Shoot me an offer.

UP FOR serotta nova special 54cm shimano ultegra carbon dura ace fizik nice in great working condition no any dents no any cracks see the pictures for the condition and for details.

Shimano Ultegra Dura Ace mix group. Ultegra crankset Overall good work order- with scratches. Low miles.

Shimano Dura Ace rear derailleur and chain. Stock brake calipers with cork pads. Fork steerer has plenty of material left to cut. It currently has 2" of spacers plus the stem.

Adamo saddle is in excellent condition. Includes an Aerodrink bottle with bar mount and a Cateye wireless computer. In fact. A Zipp will NOT work on the rear of this bike. They're reasonably light and aero but with a bike like this you'll probably want something better if you're Comes with Hed skewers. Cassette and Vittoria Rubino Pro slicks.

Rider size: The rider of this bike is a bit under 5'10" with average build. From the center of the crank to the middle of the saddle rails is just under 28" The saddle a t maximum height would be With the optional clamp not included it could go to a maximum of They were just sold in another auction. The bike is disassembled and ready to ship.

Discount for local pickup since I won't have to ship. Continental US and Canada preferred. If payment method is secure I'd consider international but you would have to pay for the shipping and add a day of handling time. The wheels would ship in a separate box. If you have any questions please ask. Cassette and skewers, including standard shipping. This is a one owner bike and was used as a race day only rig.

Though it is 10 years old, it only has about miles on it. Frame is aluminum with carbon fork. No dents or serious dings just a handful of paint chips as shown in the pics and some wear to the decals on the top tube. Shifters are Dura-Ace and everything else cranks. Brakes, deraileurs, cassette are Ultegra. Wheels are Bontrager Race Lites which were used on a few bikes over the years so I'm not sure of mileage but they are in good condition. Was state of the art in its Da Privatverkauf.

Bei Fragen einfach mailen. Siehe auch meine anderen Auktion. Size is BMC 50cm. See picture for TT length. Bike came standard with Shimano Ultegra Di2. But I've upgraded components. Bike is a smooth ride and Shimano Di2 electronic shifting has worked flawlessly.

Bike has never been raced. Taken out occasionally on the weekends. Purchased back in Sept. Bike has about miles on it. Components have less mileage since upgrades were made over the time I've owned it.

It's a really nice bike and smooth to ride. Thought I'd get into road biking, but don't have the time. For geometry. Bike comes with Shimano battery charger unit. Paypal Payment only. Shipping only to an address in the contiguous U. No overseas shipping. Shipping via Fedex Ground. Insured and you must sign for package.

This bike does not come with the charger. You will need to get one and charge the battery before use. Picture 7 shows a small scratch. The other mark is just a greese smudge and is gone. All bikes are professionally packaged and shipped within 48 business hours upon receiving payment.

Please contact us with any questions or concerns. Your business is important to us. Paypal is easy! You can even pay with your credit card thro. Description Up for auction is a Trek Madone 6. Ultegra shift levers. Ultegra brake calipers. The wear on this bike includes: a few scratches on the top tube, chipping under the down tube, a scratch on the seatstay, and a small scratch on the rear derailleur. More Photos and Details below. Please check out my Please also check out my other items!

Example feedback from my other sales"Brilliant seller. A credit to ebay. Well packaged and fast delivery. Highly recommended. Thanks" Great seller. Great product. Prompt postage. Courtesy emails. Polite service" Get the Best Service here with the-pedal-pushe.

This Bike is in mint Condition and Professionally Maintained There is no more than miles on this bike. The frame is flawless and in perfect condition. Please let me know if you have any questions. Thank you. Up for auction is a nice frameset purchased new in i Kestrel talon SL complete road bike.

The frame is a 59cm and is in excellent condition both mechanically and cosmetically. The bike has less than 3k miles since new. It is built up nicely with solid Dura-Ace and Ultegra groupo and Mavic Ksyrium Elite's with upgraded ceramic bearings. Shifters, Shimano Dura Ace. Bike will be professionally packed and shipped after payment is received.

This is a great looking full carbon BMC road bike. This bike is showing minor signs of wear including: a scratches on the shifters, a chip on the down tube and top tube, a small scuff on the saddle and a few small marks from road debris.

We have posted detailed high resolution photos of the wear. Small Felt Triathlon Bike in excellent condition. Includes Dura Ace rear derail. Bars are Zipp with Shimano shifters. Includes Shimano speed pedals. Rims are clincher HED with full disk in back.

I will leave the tires on but they look to have some dry rot cracks. This is an opportunity to get a high end component bike at a discount price. Copenhagen Observatory. Ann Arbor. Wolf, A. Mount Hamilton. Wolf , A. Wolf, L. Wolf , L. Wolf , P. Mount Wilson. Amorphous ABA type block aliph. These materials can be prepd. ROTEP reactions and can exhibit a range of phys.

Ring-opening polymn. The morphol. Several triblocks adopted well-ordered microphase-sepd. The Flory-Huggins interaction parameter was detd. The elastomeric mech. Biobased and environmental-friendly polylactones provide a soln. MW up to Chain extension reactions of the obtained pentablock copolymers are carried out using L-lysine diisocyanate LDI to produce multiblock copolymers with relatively high MW. We employ tensile tests to assess mech.

Considering the biorenewable resource of DL and LLA, a novel, biobased, biodegradable, and biocompatible elastomer is successfully synthesized. A one-pot, one-catalyst, sequential ring-opening transesterification polymn.

ROTEP was used to prep. The temp. TODT values of four sym. LDL triblock polymers. Uniaxial extension tests revealed a dramatic dependence of the room-temp. LDL n multiblocks led to substantial increases in the ultimate elongation and tensile stress at break. Because of this, it was possible to process LDL n using injection molding. The simple synthetic procedure and melt processability of the LDL n multiblock polymers make these multiblocks attractive as renewable thermoplastic elastomers TPEs.

The production of mechanically tunable block polymers from sugar Proc. Xiong, Mingyong; Schneiderman, Deborah K. National Academy of Sciences. Development of sustainable and biodegradable materials is essential for future growth of the chem. For a renewable product to be com. Few biobased polymers have met this formidable challenge. We further demonstrate that block copolymn.

This comprehensive strategy offers an economically viable approach to sustainable plastics and elastomers for a broad range of applications. Tuning thermal properties and microphase separation in aliphatic polyester ABA copolyesters Polym. MacDonald, J. Royal Society of Chemistry.

ABA triblock copolymers were prepd. Characterization of these copolymers detd. DSC anal. Copolymers prepd. The polymers could be readily cast into flexible films and their improved tensile properties were explored. The high ceiling temp. The apparent rate const. The triblock copolymer had an elongation-at-break times greater than that of pure poly L-lactide. These properties result in phase sepn. New resorbable and elastomeric ABA tri- and multiblock copolymers have been successfully synthesized by combining ring-opening polymn.

Five different poly L-lactide-b-1,5-dioxepanone-b-L-lactide triblock copolymers and one new poly L-lactide-b-1,5-dioxepanone multiblock copolymer have been synthesized. The triblock copolymers were obtained by ring-opening polymn. The new multiblock copolymer was prepd. It was possible to tailor the hydrophilicity of the materials by changing the DXO content. The tensile properties of the copolymers were controlled by altering the PDXO block length.

The copolymers retained very good mech. Schneiderman, Deborah K. Batch ring opening transesterification copolymn. Reactivity ratios detd. The new combinations of monomers presented in this work were evaluated in order to create an elastic material for potential application in soft tissue engineering. The block copolymers were designed in such a way that poly trimethylene carbonate-co-1,5-dioxepanone formed an amorphous middle block and the poly L-lactide PLLA formed semicryst.

Differential scanning calorimetry and dynamic mech. The mech. All of the copolymers synthesized showed a highly elastic behavior. The properties of copolymers could be tailored by altering the proportions of the different monomers. Aliphatic polyester block polymers: renewable, degradable, and sustainable Acc. A review. Nearly all polymers are derived from nonrenewable fossil resources, and their disposal at their end of use presents significant environmental problems. Nonetheless, polymers are ubiquitous, key components in myriad technologies and are simply indispensable for modern society.

An important overarching goal in contemporary polymer research is to develop sustainable alternatives to "petro-polymers" that have competitive performance properties and price, are derived from renewable resources, and may be easily and safely recycled or degraded.

However, property profiles of polyesters derived from single monomers homopolymers can limit their applications, thus demanding alternative strategies. One such strategy is to link distinct polymeric segments in an A-B-A fashion, with A and B chosen to be thermodynamically incompatible so that they can self-organize on a nanometer-length scale and adopt morphologies that endow them with tunable properties.

For example, such triblock copolymers can be useful as thermoplastic elastomers, in pressure sensitive adhesive formulations, and as toughening modifiers.

Inspired by the tremendous utility of petroleum-derived styrenic triblock copolymers, we aimed to develop syntheses and understand the structure-property profiles of sustainable alternatives, focusing on all renewable and all readily degradable aliph.

Building upon oxidn. Using a diol initiator and controlled catalysis, menthide was polymd. These new materials were microphase-sepd. More recently, new triblocks were prepd. These materials exibited impressive mech.

In sum, success in the synthesis of fully renewable and degradable ABA triblock copolymers with useful properties was realized. This approach has great promise for the development of new, sustainable polymeric materials as viable alternatives to nonrenewable petroleum-derived polymers in numerous applications.

Aliphatic Polyesters II. The mechanisms of biodegrdn. However, the rate of the first stage of the degrdn. Poly DL-lactide differed from the other polyesters studied, the rate of chain scission increasing after the commencement of wt. The rate of wt. Triblock polymer contg. Natural mol. We deliver this perspective primarily based on a monomer approach. Biomass-derived monomers are sepd. A variety of emerging synthetic tools controlled polymn. An overview on future opportunities and challenges, which are crit.

Omega-hydroxyfatty acids are excellent monomers for synthesizing a unique family of polyethylene-like biobased plastics. Here we report the engineering of a strain of the diploid yeast Candida tropicalis to produce com. To develop the strain we identified and eliminated 16 genes encoding 6 cytochrome Ps, 4 fatty alc. We also show that fatty acids with different chain lengths and degrees of unsatn. Biocatalysis using engineered C. Natural products as biofuels and bio—based chemicals: fatty acids and isopreneoids Nat.

Covering: to Although natural products are best known for their use in medicine and agriculture, a no. This review summarizes recent work on fatty acid-derived compds. Combining biological and chemical approaches for green synthesis of chemicals Curr.

Recent advances in the controlled ring-opening polymn. For comparison, polymn. Progress in stereo-controlled polymn. The std. The derived std. The thermodn. Specifically, the ability of these monomers to polymerize has been related to the strain of the rings, the Gibbs free energy of simple models for ring-opening reactions of the cyclic lactones, and the conformational preferences of linear model compds.

Polymerizability of 1,4-dioxanone has been found to be favored, even though less than that of. Two factors explain these features: i the strain of the ester group in the lactones increases with the exergonic character of the ring-opening process, and ii the stability of coiled conformations in model compds.

Finally, the influence of the environment on the polymerizability of the three cyclic lactones is discussed in detail. This no. Kinetic studies indicate that all the polymns. To explain this anomaly, we have applied quantum mech. The bulk ring-opening polymn. The equil. The polymn. The product triblock exhibited two distinct glass transitions temps. Comparison of Chemical and Enzymatic Polymerizations.

The kinetics of bulk polymn. Instantaneous concns. This kinetic behavior, pointing to the const. The following order of polymn. The order of rates of the enzymic polymn. The resulting difference in the orders of lactone reactivities in chem. The ring strain, which decreases with increasing lactone size, is partially released in the transition state of the elementary reaction of the polyester chain growth, which eventually leads to faster propagation for more strained monomers in chem.

Further development will be required to improve sensor design for easy integration into continuous bioprocessing systems Fisher et al. In a study by Kornecki and Strube , in-situ turbidity and ex-situ Raman spectroscopy measurements were combined with an offline macroscopic Monod kinetic model in order to predict substrate concentrations in CHO cultivations in bioreactors. In another study, high-throughput MALDI mass spectrometry based on a microarray technology was used to observe N-glycopeptides of IgG1 produced in a perfusion cell culture Hajduk et al.

Different approaches for the determination of critical timepoints for product stability in an E. An on-line method to control and manipulate glucose was studied and was validated to produce various recombinant therapeutic proteins across cell lines with different glucose consumption demands; it was then successfully demonstrated on micro 15 ml -, laboratory 7 l -, and pilot 50 l -scale systems Goldrick et al.

For a P. LC-MS metabolomics at three bioreactor scales 10 l, l, and 1, l were utilized to gain insight into the basal metabolic states of the CHO cell culture during fed-batch, and this was demonstrated as a useful technique to obtain physiological information on the cell culture state during a bioprocess, regardless of scale Vodopivec et al. It remains a challenge to set up a universal mechanistic model for processes dealing with mammalian cells because of the lack of full knowledge of metabolic networks and reaction pathways.

A hybrid semi-parametric model containing mechanistic and machine-learning methodologies has emerged as a potential tool for bioprocess development Pinto J. In one study, a mathematical model to describe polio virus production in batch bioreactors was developed and was able to accurately describe its production by Vero cells Jiang Y.

The combination of mechanistic growth models with a parallel mini-bioreactor system for E. A hybrid model was studied using a 3. A simple techno-economic model for mAbs production was also studied that can be used for any production platform Mir-Artigues et al. Various other modeling approaches to optimize bioprocesses have also been studied Gangadharan et al.

A three-dimensional computational fluid dynamics CFD model was established for the analysis of the influence of baffle structure on the flow field in orbitally shaken bioreactors OSRs , and it was proposed that the shear stress was gentle for mammalian cell growth Zhu et al. Further, a three-dimensional CFD model for hollow OSRs was established and validated, and it was verified that the hollow cylinder wall could improve the mixing efficiency Zhu et al. CFD simulations were also applied to analyze and compare microfluidic single-cell trapping and cultivation devices Ho et al.

In a study by Li et al. The development of continuous perfusion bioreactor cultures provides cost and performance benefits to biopharmaceuticals producers Somasundaram et al. This process continues for over a month or so, requiring an optimized process and cell-line stability to yield the largest amount of proteins. In a perfusion bioreactor, a harvest port and a bleed port are fitted to avoid the accumulation of toxic metabolites and to attain more viable cell density values Karst et al.

Novel types of cell retention technique, such as alternating tangential flow ATF filtration, have been developed and used in perfusion bioreactors for recombinant protein manufacturing as well as the most commonly used TFF and spin filters Rathore et al.

In order to enhance the perfusion process yield, the bleed rate should be low Lin et al. In ATF filtration, a diaphragm pump provides a flow of cell broth in alternating directions with a cycle time of about 1 min, and without additional shear stress and possible fouling Gronemeyer et al. Karst et al. To overcome the product retention problem associated with TFF- and ATF-based perfusion cultures, a large pore size hollow fiber was recently used and drastically reduced product retention Wang et al.

In another study, temperature was established to be an important parameter in perfusion culture performance optimization Wolf et al. Comparative evaluation of fed-batch and perfusion platforms for IgG1- and IgG4-producing cell lines was carried out with ATF filtration, and perfusion was found to have 7.

In another study, a two-step procedure [first, finding a suitable minimum value of the cell-specific perfusion rate CSPR at constant perfusion rate P or constant viable cell density VCD and second, investigating steady states at constant CSPR but elevated values of VCD and P] was developed for the design and development of CHO cell perfusion cultures and enabled high product yield and improved process performance with minor change in product quality Wolf et al.

A high-capacity microscale system for perfusion culture using in-situ gravity settling and automated sampling was studied, and the suitability of this platform for the evaluation of the performance of cell lines and the effects of process parameters for perfusion cultures were demonstrated Sewell et al.

The downstream purification process is of great importance, since it contributes to the approval of therapeutic products for human use Owczarek et al. Conventionally, recombinant proteins are purified using centrifugation-, chromatography-, and membrane filtration-based purification steps. Apart from these steps, viral inactivation is also used for recombinant biopharmaceuticals produced using mammalian cells Zydney, Cell disruption is required for recovery of the desired proteins, expressed as intracellular IBs Ehgartner et al.

The commonly used cell disruption methods at large scale include high-pressure homogenizers and bead mills Mevada et al. A flow chart for the purification of IB-expressed recombinant protein is shown in Figure 2.

This includes cell harvesting using centrifugation, cell lysis, IB solubilization, refolding, diafiltration, and chromatographic purification steps to obtain purified and biologically active protein. Figure 2. Flow chart of the purification of recombinant proteins expressed as IBs using E. Centrifugation, depth filtration, and tangential flow microfiltration TFF-MF are the most commonly used techniques for cell harvesting and cell separation Besnard et al. The various clarification technologies used for the downstream processing of antibodies have been described elsewhere Singh et al.

Refolding of proteins is necessary to attain biological activity for IB-expressed recombinant proteins. Batch mode refolding of solubilized IBs can be carried out using rapid or pulse dilution, by diafiltration and dialysis or by on-column chromatographic methods. In a recent study, it was also established that mild solubilization can be considered in terms of cost, time, and tag-free nature for the recovery of scFv from IBs Sarker et al.

The various methods used for refolding to recovery biologically active proteins have been reviewed previously Rathore et al. A flow chart tracking the purification of extracellular and periplasmic space-expressed recombinant proteins is shown in Figure 3. For extracellular-expressed recombinant proteins, post-cell harvesting purification steps include chromatography processes and diafiltration whereas, for periplasmic space-expressed recombinant proteins, the steps include cell lysis, centrifugation, microfiltration, chromatographic purifications, and diafiltration.

Figure 3. Flow chart of the purification of extracellular and periplasmic space-expressed recombinant proteins. Various chromatography techniques, namely affinity, ion exchange, hydrophobic interaction, and size exclusion or gel filtration chromatography, are used to purify recombinant protein-based biopharmaceuticals to achieve a high purity product with a biologically active form Saraswat et al.

It is well-established that an increased product concentration in the upstream process leads to a higher volume of chromatography resin and a higher buffer requirement. HCPs are the main source of impurities, and the HCPs of each process vary significantly from each other in their molecular mass, charge, hydrophobicity, and structure. Therefore, they present a challenge for chromatographic purification.

It is possible to reduce the HCP production during upstream process development. Cell lines producing HCP at a lower level should be selected during upstream process development to aid efficient product purification Gronemeyer et al. Affinity chromatography AC is popular and is the most selective technique used for purification of tagged proteins, bispecific antibodies, DNA-based biologics, cellular products, viral vectors, and viruses Zhao et al.

Protein A chromatography is the most widely used method for mAb purification Gronemeyer et al. The main problem associated with this chromatography is Protein A leachability, with non-specific binding of host cell protein, DNA, and other cell culture-derived impurities. Thus, it is necessary to recover these impurities using other chromatography techniques Tarrant et al. Ion exchange chromatography is the most widely used and cost-effective method for the purification of recombinant proteins.

The efficacy of a weak anion exchanger on the isolation of rHBsAg VLPs from aggregated structures was also examined, and it was found to yield a 94— Viral safety is a critical concern for therapeutic proteins such as mAb produced using mammalian cells such as CHO cells. It was also reported that CEX carried out in overloaded mode was able to remove viruses during the manufacture of mAbs Masuda et al.

Hydrophobic interaction chromatography HIC is based on the relative hydrophobicity of the protein molecules. HIC is mostly utilized as a polishing step for the purification of recombinant proteins.

In HIC, at high ionic strength, binding of proteins to ligands occurs whereas, at low ionic strength, elution of proteins occurs McCue, ; Fekete et al.

Size exclusion chromatography SEC or gel filtration chromatography separates protein molecules based on their molecular weight. SEC is used for the purification of various proteins such as scFv and insulin-like growth factor receptor Levin et al.

Membrane-based chromatography processes have also emerged as a good choice for recombinant protein purification. In this type of chromatography, a specific ligand is attached to microfiltration membrane pores.

The impurities present in protein solutions bind to the membrane at neutral to slightly basic pH and low conductivity. The optimization parameters for protein purification using membrane-based chromatography include membrane size distribution and thickness and flow distribution Orr et al. Hydrogel and nanofiber base matrices of membranes offer a high specific area, higher ligand density, and an optimized 3D binding environment Liu et al.

It was also reported that the use of nanofibers within the membrane systems of affinity chromatography could represent a significant improvement over the current offerings for viral vector purification Challener, Due to the variable nature of the process and product-related impurities, it is not possible to purify a protein using single-step chromatography.

Multimodal or mixed-mode chromatography involves selective interactions between the chromatography ligand and protein molecule through either ionic, hydrophobic, hydrogen bonding, or Van der Waals interactions. Mixed-mode resin can offer salt-tolerance, better separation, and higher binding capacity Kallberg et al.

The use of Capto resins GE is based on hydrophobic and ionic interactions, and that of Ceramic Hydroxyapatite CHT is based on electrostatic interaction and affinity interaction. MMC was successfully used as a capture step using hydrophobic charge-induction chromatography Maria et al.

The overall virus recovery in these chromatography steps was Ultrafiltration is used for purification and protein concentration Ledung et al. The application of a filter aid diatomaceous earth coupled with crossflow ultrafiltration was also studied to remove contaminant proteins and DNA molecules without the use of chromatographic steps Palombarini et al. The combination of single-pass TFF concentration and AEX chromatography was also used for an intensified mAb polishing step that improved both manufacturing flexibility and process productivity Elich et al.

An efficient chromatin-directed clarification process for cell culture fluid, an alternative to Protein A chromatography, was developed for IgG purification to remove most host DNA and histones as well as to reduce non-histone HCPs.

This allowed TFF to concentrate clarified supernatant and carry out buffer exchange, and cation exchange chromatography effectively removed the remaining host impurities to meet all clinical requirements Liu W. Some other downstream processing steps, including aqueous two-phase extraction ATPE , precipitation, and crystallization, were also used for recombinant protein preparation based on the requirements of various expression host systems Hong Yang et al.

Preparative protein crystallization was well-described in a recent review Hubbuch et al. Recent developments in downstream purification processes include the use of high-throughput devices, single-use systems, QbD and PAT, modeling, continuous downstream processing, and integrated continuous downstream processing.

High-throughput HT technologies have become an important aspect of downstream process development because of their potential to rapidly gather more data related to the process in comparison to traditional laboratory-scale techniques Benner et al.

For E. HT refolding systems for IB-expressed proteins are also available commercially and are listed in Table 5 Baumann and Hubbuch, , together with some of the other HTP devices used in downstream process development. Table 5. HT chromatography systems with different capacities are available Rege et al. Bind and elute evaluations for mAbs and amyloglucosidase have been carried out using pre-packed PreDictor filter plates GE.

In a recent study, the pairing of MiniColumns and Tecan liquid handlers was used to run up to eight chromatography conditions in one experiment Benner et al. An automated HT batch-binding screen using a well-filter-plate Seahorse Bio for CEX resins was efficiently optimized for step elution to increase purity and yield for antibodies McDonald et al. An HT method based on a microtiter filter plate [well with MultiScreen HTS Vacuum Manifold Merck-Millipore ] was applied to determine the adsorption properties and evaluate the optimal conditions for human serum albumin HSA isolation with four MM resins and two IEX resins; the findings were verified by laboratory-scale column chromatography Chu et al.

In another study, an HT process development workflow integrated with a microscale chromatography, DoE, and multivariate data analysis was studied and provided a rational method for screening resins and process parameters Stamatis et al.

In a study by Andar et al. A fold decrease in buffer, resin, and time of purification was observed in comparison to conventional columns for similar protein yields. In a recent study, using well-plates containing nickel-functionalized membranes, rapid screening of parameters for membrane protein purification was successfully performed Feroz et al.

Mixed-mode resins ionic and hydrophobic interactions were used in a plate-based HT screening platform for the selection of process parameters to achieve high purity and high overall yield of osteopontin Guo et al. A novel microfluidics-based methodology to carry out speedy and multiplexed screening of several MM ligands relative to their potential to bind different target molecules was studied using an artificial mixture containing IgG and BSA, labeled with different thiol-reactive neutral fluorescent dyes.

The study report suggested that this strategy can potentially be utilized as a predictive analytical tool in the context of purification of mAb Pinto I.

The benefits of a HT chromatography system include its availability to predict design space for dynamic binding capacity DBC , collect data for the prediction of elution behavior, and allow significant investigation using DoE McDonald et al. HT chromatography systems have limitations in their potential to reveal the flow distribution of process columns Singh and Herzer, Noyes et al. This study indicated the existence of two different fouling mechanisms: an irreversible and a reversible mechanism Bieberbach et al.

The performance of a pilot-scale TFF system was predicted by devising an ultra scale-down USD device consisting of a cell stirred using a rotating disc 2. Aqueous two-phase extraction has the potential to selectively separate proteins from unclarified cell culture supernatants directly. For single-use or disposable cell harvesting, two main options, namely a single-use centrifuge followed by single-use depth filters or single-use depth filters alone, are used.

Single-use depth filters are more common due to the commercial unavailability of single-use large-scale centrifuges Boedeker et al. The Unifuge is another single-use centrifuge available for cell harvesting.

Due to the development of single-use filtration techniques, primary and secondary filters can be replaced by a single filtration step. This leads to a lower cycle time, filtration surface area, and buffer requirement. Depth filters can be employed to recover cells from single-use bioreactors up to the 2, l scale.

However, the number of systems needed for a 2, l bioreactor culture is greater, so their use should be analyzed with respect to cost, space, waste, footprint, etc.

Boedeker et al. The depth filters have advantages like ease of scalability, better recovery, consistency, and low cost Collins and Levison, However, some issues associated with single-use depth filters include the binding of proteins or DNA Gupta and Shukla, c. Single-use chromatography systems can be utilized for the purification of recombinant proteins from culture harvested from an up to 2, l bioreactor, depending on product titers, the loading capacity of the column, and process flow rates.

Such a system is supported by pinch valves, sensors, and pumps Boedeker et al. Single-use TFF systems Pall and Merck-Millipore are commercially available for downstream purification, and these systems consist of pumps, pinch valves, a tank, sensors, and tubing manifolds Boedeker et al. The use of DoE has also been established to increase the performance of downstream process development. In one study, high-pressure homogenization was used to screen critical process parameters CPPs using DoE to enhance product titer and achieve adequate product quality, based on predefined critical quality attributes CQAs Pekarsky et al.

In downstream processing, PAT tools are used for the analysis of protein concentration, its purity, host cell proteins, host cell DNA, endotoxin, variants misfolding , and process-related impurities.

For these purposes, spectroscopy, spectrometry, HPLC, circular dichroism, and other tools are used to monitor critical quality attributes in chromatography processes. Next-generation sequencing could be used for virus screening, but it is very sophisticated. Further studies are needed to determine the critical points to assure the viral safety of therapeutic proteins Fisher et al.

Modeling and simulations can significantly decrease the number of experiments needed while increasing or collecting experimental data Hanke and Ottens, Empirical models are based on a priori identified output data within a defined design space, and mechanistic models are based on physicochemical properties Baumann and Hubbuch, Mechanistic modeling is an important process development tool that has been used for chromatography to speed up process development.

These models can explain the downstream unit operation at a level of detail that depends on the application Benner et al. The use of a mechanistic model of HIC as a PAT tool for pooling decisions to enable aggregate removal for a mAb resulted in higher product purity with respect to offline column fractionation-based pooling Shekhawat and Rathore, b.

An approach toward statistical process control and monitoring of protein refolding during the production of recombinant therapeutic proteins from E. This approach used on-line measurements of redox potential, temperature, and pH for the development of a statistical model. This was successfully demonstrated to ensure the quality of the manufactured product consistently.

Early-stage bioprocess development faces the issues of the definition of optimal operating parameters. Polishing chromatography of a mAb from a challenging ternary feed mixture was optimized by a hybrid approach of the simplex method and a form of local optimization. The findings of the study showed it to be perfectly suitable for the speedy development of bioprocessing unit operations Fischer et al. An overview of mechanistic modeling of liquid chromatography was given in a recent study Shekhawat and Rathore, a.

The shift from a traditional batch process to a continuous process for any product can reduce cost Schofield, Systems and techniques for continuous downstream processing of biopharmaceuticals have been developed and used for process development and scale-up. The various technologies of continuous bioprocessing are shown in Figure 4.

Continuous centrifugation and TFF-MF are the main methods utilized for cell harvesting or cell removal. Disk stack and tubular bowl centrifuges have been used in continuous operation for the harvesting of a recombinant E. A disk-stack continuous centrifuge with periodic and continuous discharge was also used for large-scale clarification of high cell density CHO cell culture for IgG1 mAb production Richardson and Walker, The cell lysis techniques mechanical type used in continuous mode are high-pressure homogenization and bead milling.

In a study by Haque et al. Figure 4. Flow chart of the different technologies within continuous bioprocessing. With the aim of bypassing this fast and irreversible inactivation, we study the use of a gradual supply of hydrogen peroxide to maintain its concn.

In this contribution, we report a multienzymic cascade for in situ generation of hydrogen peroxide. Reduced NADH was reoxidised by the redn. Finally, this system was coupled to the hydroxylation of ethylbenzene reaction catalyzed by an evolved peroxygenase from Agrocybe aegerita rAaeUPO. The use of natural deep eutectic solvents NADES as multifunctional solvents for limonene bioprocessing was reported.

NADES were used for the extn. The proof-of-concept for this multifunctional use was provided, and the scope and current limitations of the concept were outlined.

Peroxygenases catalyze a broad range of stereo selective oxyfunctionalization reactions. However, to access their full catalytic potential, peroxygenases need a balanced provision of hydrogen peroxide to achieve high catalytic activity while minimizing oxidative inactivation.

Herein, we report an enzymic cascade process that employs methanol as a sacrificial electron donor for the reductive activation of mol. Full oxidn. Overall we propose and demonstrate an atom-efficient and easily applicable alternative to established hydrogen peroxide generation methods, which enables the efficient use of peroxygenases for oxyfunctionalization reactions.

ACS Catal. Willot, Sebastien J. American Chemical Society. Peroxygenases require a controlled supply of H2O2 to operate efficiently. Here, we propose a photocatalytic system for the reductive activation of ambient O2 to produce H2O2 which uses the energy provided by visible light more efficiently based on the combination of wavelength-complementary photosensitizers.

This approach was coupled to an enzymic system to make formate available as a sacrificial electron donor. The scope and current limitations of this approach are reported and discussed. Nature Research. Peroxygenases offer an attractive means to address challenges in selective oxyfunctionalization chem. Despite this, their application in synthetic chem. Often atom-inefficient peroxide generation systems are required, which show little potential for large-scale implementation.

Here, we show that visible-light-driven, catalytic water oxidn. In this way, the stereoselective oxyfunctionalization of hydrocarbons can be achieved by simply using the catalytic system, water and visible light. Zhang, Wuyuan; Burek, Bastien O. Selective oxyfunctionalizations of inert C-H bonds can be achieved under mild conditions by using peroxygenases.

This approach, however, suffers from the poor robustness of these enzymes in the presence of hydrogen peroxide as the stoichiometric oxidant. Herein, we demonstrate that inorg. Peroxygenases are very promising catalysts for oxyfunctionalization reactions. Their practical applicability, however, is hampered by their sensitivity against the oxidant H2O2 , therefore necessitating in situ generation of H2O2.

Here, we report a photoelectrochem. When tethered on single-walled carbon nanotubes SWNTs under illumination, flavins allowed for a marked anodic shift of the oxygen redn. This flavin-SWNT-based photoelectrochem. Specific Photobiocatalytic Oxyfunctionalization Reactions. The present work demonstrates that the arom.

In situ generation of H2O2 via photochem. Under nonoptimized reaction conditions the enzyme turnover nos. In vitro cofactor supply and regeneration have been a major obstacle for biocatalytic processes, in particular on a large scale.

Peroxidases often suffer from inactivation by their oxidative co-factor. Combining photocatalysis and biocatalysis offers an innovative soln. Herein, we show that redox-active buffers or even water alone can serve as efficient, biocompatible electron sources, when combined with photocatalysis.

Mechanistic investigations revealed first insights into the possibilities and limitations of this approach and allowed adjusting the reaction conditions to the specific needs of biocatalytic transformations. Proof-of-concept for the applicability of this photobiocatalytic reaction setup was given by enzymic halogenations. Photo-Biocatalysis: Biotransformations in the Presence of Light. Feyza; Barone, Giovanni D. Light has received increased attention for various chem. Because currently only a few enzymic reactions are known, which per se require light, most transformations involving light and a biocatalyst exploit light either for providing the cosubstrate or cofactor in an appropriate redox state for the biotransformation.

In selected cases, a promiscuous activity of known enzymes in the presence of light could be induced. In other approaches, light-induced chem. This Review gives an overview of the various approaches for using light in biocatalysis.

UV photoreactors. FEBS Lett. The mushroom Agrocybe aegerita secretes a peroxidase AaP that catalyzes halogenations and hydroxylations. Phenol was brominated to 2- and 4-bromophenol ratio and chlorinated to a lesser extent to 2-chlorophenol. The purified enzyme was found to oxidize toluene via benzyl alc. A second fraction of toluene was hydroxylated to give p-cresol as well as o-cresol and methyl-p-benzoquinone.

The UV-Vis absorption spectrum of purified AaP showed high similarity to a resting state cytochrome P with the Soret band at nm and addnl. AaP regioselectively hydroxylated naphthalene to 1-naphthol and traces of 2-naphthol ratio H2O2 was necessarily required for AaP function and hence the hydroxylations catalyzed by AaP can be designated as peroxygenation and the enzyme as an extracellular peroxygenase.

American Society for Microbiology. Agrocybe aegerita, a bark mulch- and wood-colonizing basidiomycete, was found to produce a peroxidase AaP that oxidizes aryl alcs. The enzyme also catalyzed the oxidn. The optimum pH for the oxidn. The N-terminal amino acid sequences of the main AaP II spots blotted after two-dimensional gel electrophoresis were almost identical and exhibited almost no homol. This finding is consistent with the fact that AaP halogenates monochlorodimedone, the specific substrate of CPO.

The existence of haloperoxidases in basidiomycetous fungi may be of general significance for the natural formation of chlorinated org. Enzyme Microb. Unspecific peroxygenase UPO is a highly efficient biocatalyst with a peroxide dependent monooxygenase activity and many biotechnol. Recently, the UPO from Agrocybe aegerita was evolved for secretion and activity in Saccharomyces cerevisiae [8]. In the current work, we describe a tandem-yeast expression system for UPO engineering and large scale prodn.

By harnessing the directed evolution process in S. While secretion levels were found similar for both yeasts in flask fermn. The P. Thus, this tandem-yeast expression system ensures the engineering of UPOs to use them in future industrial applications as well as large scale prodn. Directed Evolution of Unspecific Peroxygenase from Agrocybeaegerita. Applied and Environmental Microbiology , 80 11 , , 13 pp.

Unspecific peroxygenase UPO represents a new type of heme-thiolate enzyme with self-sufficient mono per oxygenase activity and many potential applications in org.

With a view to taking advantage of these properties, we subjected the Agrocybe aegerita UPO1-encoding gene to directed evolution in Saccharomyces cerevisiae. To promote functional expression, several different signal peptides were fused to the mature protein, and the resulting products were tested. Over 9, clones were screened using an ad hoc dual-colorimetric assay that assessed both peroxidative and oxygen transfer activities. After 5 generations of directed evolution combined with hybrid approaches, 9 mutations were introduced that resulted in a 3,fold total activity improvement with no alteration in protein stability.

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  5. Peroxygenases are very interesting catalysts for specific oxyfunctionalization chemistry. Instead of relying on complicated electron transport chains, they rely on simple hydrogen peroxide as the stoichiometric oxidant. Their poor robustness against H2O2 can be addressed via in situ generation of H2O2. Here we report that simple graphitic carbon nitride (g-C3N4) is a promising photocatalyst to Cited by: 6.
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