Convergent Synthesis of Digitally-encoded Poly ( alkoxyamine amide ) s

Binary-encoded poly(alkoxyamine amide)s were prepared by oligomer ligation. These polymers contain digital sequences based on two monomers defined as 0 and 1 bits. A library of oligomers containing all possible dyads 00, 01, 10 and 11 was prepared and used to construct long coded sequences.


D. References S13
Electronic Supplementary Material (ESI) for ChemComm.This journal is © The Royal Society of Chemistry 2015
Copper-(I)-bromide (Sigma-Aldrich, 98%) was washed with glacial acetic acid in order to remove any soluble oxidized species, filtered, washed with ethanol, and dried.2-Bromopropionic anhydride (a-0) and 2-bromoisobutyryl anhydride (a-1) were synthesized as previously reported.to swell the resin with DCM prior to the reaction.The anhydride (5 Eq. of either a-0 or a-1), HBTU (1.326 g, 5 Eq.) and DMAP (0.427 g, 5 Eq.) were added to a glass vial containing Rw (1.0 g, 0.7 mmol, 1Eq.).To the reaction mixture, 12 mL of THF were added and stirred for 90 min in a microwave reactor (~10W, 40°C).After completion, the reaction mixture was transferred to a fritted funnel and the beads were washed with THF to remove excess reagents.
A.2.2.Attachment of the T spacer to the sequence.Amino-TEMPO (0.72 g, 6 Eq.) and Me6TREN (0.7 mL, 3.3 Eq.) were dissolved in 12 mL of anhydrous DMSO and were placed into a fritted funnel containing bromide-functionalized resin beads.The funnel was sealed with a septum and the reaction mixture was purged with argon for 15 minutes.Then, CuBr (0.35 g, 3.5 Eq.) was rapidly added.The mixture was shaken for 35 min under inert atmosphere.After completion, the solution was drained out from the funnel and the beads were washed with THF.

A.2.3. Attachment of the second coded motif by anhydride-amine coupling.
A mixture of an anhydride (5Eq. of either a-0 or a-1) and a base (18 Eq., DIPEA in case of a-0 and K2CO3 for a-1) was added to a fritted funnel for solid-phase synthesis containing amino-functionalized resin beads.The use of DIPEA is recommended when a-0 is used because it was observed that K2CO3 forms an inhomogeneous gel with this anhydride in THF. 12 mL of THF was added and the mixture was shaken for 60 min on a mechanical shaker.After completion, the solution was drained out from the fritted funnel.When K2CO3 was used, the beads were washed with MeOH-H2O (1:1) and afterwards with THF.When DIPEA was used, washing was only done with THF.
A.2.4.Cleavage of the dyads from the resin.Cleavage of the dyads from the resin was performed in TFA/DCM solution (1/1) for 2 h.After reaction, the solution was filtered, concentrated and precipitated in diethyl ether.The crude mixture was diluted in THF and small amounts of insoluble resin fragments were separated by filtration.The filtrate was concentrated by the removal of solvents and TFA.Finally the oligomers were isolated either as crystalline solid (1T1) or as precipitates from diethylether (for 0T0, 0T1, and 1T0).minutes.The deprotection step was repeated a second time to ensure complete removal of the Fmoc protecting groups from the resin beads.A Kaiser test made on few resin beads to confirm the presence of deprotected primary amine groups.

A.3.2. General procedure for anhydride-amine coupling.
A mixture of anhydride a-1 (5 Eq.) and K2CO3 (18 Eq.) was added to a fritted funnel for solid-phase synthesis containing aminofunctionalized resin beads.4 mL of THF were added and the mixture was shaken for 50 min on a mechanical shaker.After completion, the solution was drained out from the fritted funnel.
A.3.3.General procedure for radical-radical coupling.Amino-TEMPO (0.08 g, 6 Eq.) and Me6TREN (0.078 mL, 3.3 Eq.) were dissolved in 4 mL of anhydrous DMSO and were placed into a fritted funnel containing bromide-functionalized resin beads.The funnel was sealed with a rubber septum and the reaction mixture was purged with argon for about 15 minutes.Then, CuBr (0.034 g, 3 Eq.) was rapidly added.The mixture was shaken for 25 min under inert atmosphere.After reaction, the solution was drained out from the funnel and the beads were washed several times with THF.

B. Measurements and analysis.
1 H NMR and 13 C NMR spectra were recorded in CDCl3 on a BrukerAvance 400 MHz spectrometers equipped with Ultrashield magnets.Molecular weights and molecular weight distributions were determined using a SEC system equipped with a Shimadzu RiD-10A refractive index detector and five PLgel 10µ Mixed-B columns.The mobile phase was THF with a flow rate of 1 mL•min -1 using a Shimadzu LC20AD pump.Toluene was used as internal reference.The molecular weight calibration was based on sixteen narrow molecular weight linear polystyrene standards from Polymer Laboratories.High resolution MS and MS/MS experiments were performed using a QStar Elite mass spectrometer (Applied Biosystems SCIEX, Concord, ON, Canada) equipped with an electrospray ionization (ESI) source operated in the positive mode.The capillary voltage was set at +5500 V and the cone voltage at +75 V.
In this hybrid instrument, ions were measured using an orthogonal acceleration time-of-flight (oa-TOF) mass analyzer.In the MS mode, accurate mass measurements were performed using reference ions from a poly(propylene glycol) or a poly(ethylene glycol) internal standard.In the MS/MS mode, a quadrupole was used for selection of precursor ions to be further submitted to collision-induced dissociation (CID) in a collision cell.The precursor ion was used as the reference for accurate measurements of product ions in MS/MS spectra.In this instrument, air was used as the nebulizing gas (10 psi) while nitrogen was used as the curtain gas (20 psi) as well as the collision gas.Instrument control, data acquisition and data processing of all experiments were achieved using Analyst software (QS 2.0) provided by Applied Biosystems.
Oligomer solutions were prepared in methanol supplemented with ammonium acetate (3 mM) and introduced in the ionization source using a syringe pump (flow rate: 5 μL min -1 ).