New Boronate Monomers and Polymers By: Robert B. Login (rloginconsulting.com)

Transcription

1 ew oroate Moomers ad Polymers y: obert. Logi (rlogicosultig.com) oroate ester techology is of great iterest because esterificatio of boroic acid is spotaeous but is readily reversible ad this is especially valuable whe the alcohol is glucose because its boroate ester ca fuctio as a diabetic idicator of blood glucose or eve as a isuli release mechaism. A recet excellet review goes ito great detail cocerig this iterestig chemistry. rooks, William LA, ad ret S. Sumerli. "Sythesis ad applicatios of boroic acid-cotaiig polymers: From materials to medicie."chemical reviews, (2015): A simple search o Google Scholar retured thousads of boroate refereces, so it is o easy task to comprehed all of its chemistry; therefore, I limited my iterest to polymeric boroate derivatives. Viyl boroate is the first moomer to come to mid, but eve though it will polymerize, it is difficult to polymerize ad ever wet commercial. Mulvaey, J. E.,. A. ttaviai, ad J. J. Laverty. "Preparatio of viyl boroate copolymers ad reactios."joural of Polymer Sciece Part A: Polymer Chemistry, 20.7 (1982): A review of boroate chemistry will help explai my ideas. all, Deis G. "Structure, properties, ad preparatio of boroic acid derivatives. verview of their reactios ad applicatios."oroic acids: preparatio ad applicatios i orgaic sythesis ad medicie, 1 (2006): 1-99 ad d editio. Scheme 1: amig the oxidatio derivatives of borae, while boroxie ad diboroxae are aalogous to ahydrides. ecause of the empty p-orbital o boro, the boroate esters will coordiate a hydroxide to fill that orbital releasig a proto.

2 Scheme 2: (The reverse equilibrium arrow below the - should have a + to reverse the equilibrium.) As show i scheme 2, this reactio is reversible ad p depedet. The reaso is because boro has a free p orbital ad acts as a Lewis acid i water. Li, Meg, et al. "Electrochemical sesig usig boroic acids."chemical Commuicatios, (2015): If you prepare a polymer with boroate esters i ahydrous solvets the add said polymers to aqueous cotaiig solutios i which a sugar has also bee added the because of the equilibria, a trasfer of the more reactive diol will occur(p also plays a roll here as acidic p favors hydrolysis while higher p favors ester formatio). owever, the poit I'm makig is that moomers ad polymers cotaiig boroate esters are stable eough whe ot i aqueous solutio ad their sythesis ca be achieved i such ahydrous solvets without cocer. owever, i water solutio, boroic acids will form boroate esters at the pka of the boroic acid (alkalie). This is very uique because you ca mix i aqueous media, polyboroic acids with polyalcohols to form supermolecular compouds! The reactios occur upo mixig eve at T. Scheme 3: Esterificatio at alkalie p ad egative charge o boro. itroge cotaiig molecules ca replace oe of the groups because it is more ucleophilic.

3 This is just a example as the itroge ca be heterocyclic or o a separate compoud etc. Germacidal oroates A amphoteric-eutral charge Catioic acterial surface C Scheme 4: The geeral idicated quat stads for all types of quats; moomeric, polymeric or surfactats as log as they are capable of killig bacteria. The idea is that i water the catioic charge is balaced by the egative charge o boro rederig the amphoteric harmless. is the idea that the bacteria have a polymeric sugar coat that will form a boroate ester, revealig the germicidal quat where it ca do the most harm. D is the idea that the bacterial polymeric sugar coat will be more attractive ad exchage the boroate ester, freeig the quat ext to the bacterial coatig where it ca disrupt it. D ydrogels: 3,4-dihydroxypyrrolidi-2-oe Scheme 5: Proposed dihydroxy VP( groups must be cis) that ca be cross liked i aqueous solutio with diboroic acids upo mixig! Sythesis of dihydroxy moomers:

4 o, Chi Mig, Wig Yiu Yu, ad Chi Mig Che. "utheium aoparticles Supported o ydroxyapatite as a Efficiet ad ecyclable Catalyst for cis Dihydroxylatio ad xidative eavage of Alkees." Agewadte Chemie, (2004): riksma, Jelle, et al. "omogeeous cis-dihydroxylatio ad epoxidatio of olefis with high 2 2 efficiecy by mixed magaese/activated carboyl catalyst system."tetrahedro letters,43.14 (2002): Saisaha, Pattama, et al. "Magaese catalyzed cis-dihydroxylatio of electro deficiet alkees with 2 2 DI: /c0ob00102c."rgaic & biomolecular chemistry, 8.19 (2010): ataille, Carole J, ad Timothy J. Doohoe. "smium-free direct sy-dihydroxylatio of alkees."chemical Society eviews, 40.1 (2011): (the low yield might be because of steric crowdig) + u Scheme 6: Metathesis route to startig M. With VP copolymers, the 3,4-dihydroxy comoomer would form water soluble copolymers that would form iterestig ad reversible gels with boroic crosslikers suitable for deliverig (poorly soluble) drugs, A ad DA or various proteis that had bee mixed ito the copolymer before crosslikig. elease of said drugs could be accomplished if for example a sugar happeed to be preset. It could eve react through the diol with drugs derivatized with labile baroic acids as pro-drugs that would also be released whe the p was acidic. Similar gels have foud use as sugar idicators ad isuli release systems because sugars will replace the crossliks hece affordig a method to detect them (gel swellig

5 or collapse). Isuli derivatized with releasable diols (the labile diol ca be removed oce outside the gel) that ca be released by glucose. PVP based boroate copolymers would be safe vehicles for such chemistry because PVP has a excellet toxicity profile. Su, Xiaolog, ad Toy D. James. "Glucose sesig i supramolecular chemistry."chemical reviews, (2015): ' ' ' Scheme 7: Dimers of the 3,4 dihydroxy pyrrolidoe ca form liear ad brached polymers examples of which are illustrated i scheme 5. These polymers will form spotaeously i water cotaiig polyboroic acids at basic p's(pka of the boroic acid). They are examples of CF chemistry (covalet orgaic frameworks). ambo, rett M., ad Joh J. Lavige. "Defiig self-assemblig liear oligo (dioxaborole) s."chemistry of materials, (2007): Kubo, Yuji, yuhei ishiyabu, ad Toy D. James. "ierarchical supramolecules ad orgaizatio usig boroic acid buildig blocks."chemical Commuicatios, (2015): rooks, William LA, ad ret S. Sumerli. "Sythesis ad applicatios of boroic acid-cotaiig polymers: From materials to medicie."chemical reviews, (2015): cure cure

6 Scheme 8: Exocyclic acrylate type moomer idea. The five membered rig moomer would be easier to sythesize as it could be prepared from pyruvic acid ad a boroic acid. The resultig polymer could be hydrolyzed i water uder acidic coditios or by oxidatio with hydroge peroxide or with added reactive sugars. The resultig hydroxy carboxylic acid could cure (form polyesters) upo dry dow. ' rp " " Scheme 9: rp boroate moomer possibilities. XS () 2, + Scheme 10: I'm bettig that reactio with boroic acid is very fast ad will grab the desired itermediate? I'm sure there are other sythetic routes, however? ' () A Scheme 11: Polyester or polylamides are possible if the boroate esters would stad up to the catalysts ad coditios required? Moomer A results i the boroate i the

7 polymer backboe where it would be very vulerable to water hydrolysis eve more so tha the commercial polyahydrides. (..see cis-dihydroxylatio refereces) would be more hydrolysis resistat but would easily exchage with more reactive diols(sugars) as a way to expose dihydroxy groups o the polymer backboe. bviously, boro chemistry is much more tha boroic acid derivatives, eve though they are extremely importat for example i Suzuki couplig. The followig book however shows how much more there is to this chemistry. all, D. "oroic Acids Preparatio ad Applicatios i rgaic Sythesis, Medicie ad Materials Secod Completely evised Editio Preface."oroic Acids, 2 (2011). I coclusio, thak you for readig this proposal. I would welcome ay commets or suggestios. Thak you, Dr. obert. Logi (rlogicosultig.com)