Tunable Orthogonal Reversible Covalent (TORC) Bonds: Dynamic Chemical Control over Molecular Assembly

Abstract

Dynamic assembly of macromolecules in biological systems is one of the fundamental processes that facilitates life. Although such assembly most commonly uses noncovalent interactions, a set of dynamic reactions involving reversible covalent bonding is actively being exploited for the design of functional materials, bottom-up assembly, and molecular machines. This Minireview highlights recent implementations and advancements in the area of tunable orthogonal reversible covalent (TORC) bonds for these purposes, and provides an outlook for their expansion, including the development of synthetically encoded polynucleotide mimics.

Trismaleimide Dendrimers: Helix‐to‐Superhelix Supramolecular Transition Accompanied by White‐Light Emission

“…The peripherally alkyl‐modified dendrimer G 1.5 a was synthesized by using a convergent method (Figure b), where dendron b was first synthesized by the click reaction of G 0 with the secondary amine N , N ‐didodecylamine. The chemical structure of dendron b was fully characterized (see Figures S7–S9).…”

Advanced Bottom‐Up Engineering of Living Architectures

“…Alternatively, oligonucleotide‐based technologies (e.g., DNA aptamers) have also been employed for establishing programmed cell–cell connectivity into higher order cell‐rich 3D microtissue constructs. This approach is inspired by the orthogonal hydrogen bonding of nucleic base pairs naturally observed in DNA, an interaction that demands a specific template for complete binding of two complementary nucleotide sequences . Such unique cross‐reactivity has led to significant advances in other fields (e.g., DNA origami and patterning, synthetic nanopores, and molecular motors) .…”

Cell‐Penetrating Dynamic‐Covalent Benzopolysulfane Networks

“…Thed ynamic-covalent networks [16,17] of extreme sulfur species obtained from BPS 5 caused strong retention on thiol exchange affinity columns (Figure 3c vs.3 a,b). Release after addition of DTT to the mobile phase exceeded initial elution by far and was unusually slow,c ontinuing far beyond three hours (Figure 3c,s olid).…”

“…[1][2][3][4][5][6][7] This extreme sulfur chemistry attracted our attention in our search for new ways to enter cells.F rom cell-penetrating peptides (CPPs) [8] to cell-penetrating poly(disulfide)s (CPDs) [9] and COCs, [10][11][12][13] the cellular uptake via dynamic covalent dichalcogenide exchange chemistry has come to prominence,o ften referred to as thiol-mediated uptake,w ith exofacial thiols as initial targets and continuing on the way into the cell. [1] We here report that BPS 5 ,f or example, 1,o utperforms all known COCs,a nd, most importantly,t hat BPS 5 penetrate cells in an ew way,i .e., by in situ selection from adaptive dynamic-covalent networks [16,17] of extreme sulfur species with high reactivity,h igh selectivity, and strong retention by thiols. [1] We here report that BPS 5 ,f or example, 1,o utperforms all known COCs,a nd, most importantly,t hat BPS 5 penetrate cells in an ew way,i .e., by in situ selection from adaptive dynamic-covalent networks [16,17] of extreme sulfur species with high reactivity,h igh selectivity, and strong retention by thiols.…”

“…[10][11][12][13][14][15] Promising results with strained cyclic disulfides [10,11] and diselenides [12,13] called for as hift of attention to the extreme sulfur chemistry of higher oligochalcogenides. [1] We here report that BPS 5 ,f or example, 1,o utperforms all known COCs,a nd, most importantly,t hat BPS 5 penetrate cells in an ew way,i .e., by in situ selection from adaptive dynamic-covalent networks [16,17] of extreme sulfur species with high reactivity,h igh selectivity, and strong retention by thiols. Target molecules 1-8 were accessible by substantial multistep synthesis ( Figure 1, Scheme 1, and Supporting Information, Schemes S1-S3 and S5-S8).…”