High-density information storage in an absolutely defined aperiodic sequence of monodisperse copolyester

Abstract

Synthesis of a polymer composed of a large discrete number of chemically distinct monomers in an absolutely defined aperiodic sequence remains a challenge in polymer chemistry. The synthesis has largely been limited to oligomers having a limited number of repeating units due to the difficulties associated with the step-by-step addition of individual monomers to achieve high molecular weights. Here we report the copolymers of α-hydroxy acids, poly(phenyllactic-co-lactic acid) (PcL) built via the cross-convergent method from four dyads of monomers as constituent units. Our proposed method allows scalable synthesis of sequence-defined PcL in a minimal number of coupling steps from reagents in stoichiometric amounts. Digital information can be stored in an aperiodic sequence of PcL, which can be fully retrieved as binary code by mass spectrometry sequencing. The information storage density (bit/Da) of PcL is 50% higher than DNA, and the storage capacity of PcL can also be increased by adjusting the molecular weight (~38 kDa).

Fig. 1. Writing information in sequence-defined PcL.

Schematic illustration of the cross-convergent strategy to synthesize PcL with a sequence corresponding to the binary code for the 64-bit word SEQUENCE. Four dyads of phenyllactic acid (P representing 0) and lactic acid (L representing 1) were used as the constituent units of PcL. The cross-convergent pathway with four dyads could express any aperiodic P and L sequence. Tetrads were sequentially converged to form one-byte characters (shown in a red box), two-and 4-byte words, and finally PcL containing the 64-bit digital information encoding SEQUENCE. The green box indicates a set of deprotections and coupling constituting a convergent growth (a BF₃⋅Et₂O, RT, 6 h; b Pd/C, H₂, RT, 8 h; c EDC⋅HCl, DMAP, 8 h).

Fig. 2. Molecular-weight analysis of PcL.

a Gel-permeation chromatography (GPC) analysis of PcLs with 8, 16, 32, 64, 128 repeating units. b Combined MALDI-TOF mass spectra of PcLs encoding the letter (E, 1201.5 Da), two-letter word (SE, 2082.9 Da), four-letter words (SEQU, 3920.4 Da and ENCE, 3996.5 Da), 64-bit word (SEQUENCE, 7674.5 Da), and 128-bit word (SEQUENCESEQUENCE, 15105.3 Da). The peak was assigned to a [M + Na]⁺ ion. c MALDI-TOF spectra of 64- and 128-bit PcL showing no deletion errors or contamination of lower molecular-weight fragments.

Fig. 3. Decoding of sequence-defined PcL by tamdem mass spectrometry.

a Fragmentation of 8-bit PcL under MALDI-TOF MS/MS experiments showing a series of ai and yi fragments. b MALDI-TOF MS/MS spectrum of a PcL, in which 8-bit information corresponding to the letter N was stored. Two series of fragments (ai and yi fragments) could be read simultaneously in the spectrum. The PcL sequence was decoded by reading the spectrum in both directions relative to the molecular ion peak [M + Na]⁺. The deciphered chemical sequence (Si-PLPPLLLP-Bz) was converted to digital code (01001110), which represented the letter N. c Tandem mass sequencing of the entire 64-bit information stored in the PcL. The entire chemical sequence was decoded using a single mass spectrum, followed by conversion to digital information to read the word SEQUENCE (red box).

Fig. 4. MALDI-TOF mass sequencing of 128-bit PcL.

a A series of MALDI-TOF mass spectra of chemically degraded PcL via hydrolysis. The assigned peaks are marked by arrows. The mass spectra of xi fragments were used for MALDI-TOF sequencing. The sequence of the last 8 repeating units at the Bz terminus was decoded by MALDI-TOF MS/MS to avoid the noise from the signal of the matrix molecules. b The chemical structure of 128-bit PcL drawn with the decoded sequence. The repeating units are numbered in an increasing order from the first repeating unit (P) at the TBDMS terminus. The decoded sequence is identical to the encoded chemical structure.

Fig. 5. Molecular-weight analysis of monodisperse PAHs.

a The iterative convergent synthesis of poly(rac-phenyllactic acid) (PAn). The deprotection and subsequent esterification reactions shown in the red dotted box constitute a convergent growth step. The number shown with circular arrows represent an iteration of the convergent growth step. b Method to obtain the monodisperse PAHs with desired number of repeating units via combination of constituent units. TBDMS and Bz protecting groups are highlighted in green and blue, respectively. c Gel-permeation chromatography of PAs with 16, 32, 64, 128, and 256 repeating units. d Combined MALDI-TOF mass spectra of PA16 (black, 2615.2 Da), PA32 (blue, 4986.4 Da), PA64 (magenta, 9728.4 Da), PA80 (green, 12100.7 Da), PA96 (orange, 14474.0 Da), PA128 (purple, 19220.6 Da), and PA256 (red, 38191 Da). MALDI-TOF MS of PA256 was measured in a linear mode. Other samples were measured in a reflection mode. The peak was assigned to a [M + Na]⁺ ion.