On the mechanism of mechanochemical molecular encapsulation in peptidic capsules

Abstract

Molecular encapsulation of C inside a hydrogen-bond-sealed semi-flexible peptidic capsule is hindered in solution, yet it proceeds effectively after mechanical milling of a solid sample. We show that the molecular mechanism involves the generation of non-covalently disordered forms that are active in guest uptake. We also show that the solvent-free mechanochemical covalent synthesis of capsules directly results in obtaining disordered, active forms.

Ball size or ball mass – what matters in organic mechanochemical synthesis?

“…Ball-milling of solid mixtures has proved to be an efficient approach to the synthesis of organic and coordination compounds, ranging from multi-component crystals to polypeptides. [1][2][3][4][5][6][7][8][9][10] In particular, it is becoming increasingly important for obtaining pharmaceutical solids. Mechanochemical methods are attractive as environmentally benign techniques, and often permit rapid and high yield transformations.…”

Porous Molecular Capsules as Non‐Polymeric Transducers of Mechanical Forces to Mechanophores

“…For sample (3 + 4) milled ,c ontainingo nly small molecule disulfides, the sf-MALDI spectra show no traces of exchange or dissociation after milling( Figure S13 bi nt he SupportingI nformation), indicating that upon neat milling disulfide bond breakage/re-formation does not proceed for small molecules. [40] However,f or sample (1 + 7a 2 ) milled ,t he sf-MALDIs pectrum shows, in addition to the signals of the substrate [1 + H] + (relative intensity 100 %), products of the partial exchange of hydrazides from capsules 1 and 7a 2 [1 + 8a+ H] + (relative intensity 5%, 8a constitutes ac omponent of capsule 7a 2 ,s uch replacement does not demandb reaking of disulfide bonds owing to the flexibility of the cystinea rms), indicating that the presence of the covalent porous capsule triggers exchange (Figure 3d,F igure S16 in the Supporting Information). Also, the spectra of (1 + 6) milled and (1'C 70 + 6) milled show no exchange signals ( Figure S15 in the Supporting Information).…”

“…[41] Mechanistic studies support am echanism for milling-induced intermolecularr eorganization, which leads to an equilibrium population richi ng uest-filled capsular assemblies in the solid state;t hese are formed to avoid empty space in the cavities. [40] Encapsulation of fullerenesinsuch capsules is thermodynamically favored but it is hedged by ah igh kinetic barrier( owing to unfavorable capsuleo pening). Ad ifferent mechanism was postulated by our group for encapsulation of fullereneg uests in peptidic capsules-also non-covalent species, but conformationally labile and pre-organized.…”

Self-Assembly of a Chiral Cubic Three-Connected Net from the High Symmetry Molecules C60 and SnI4

“…22,[25][26][27] Furthermore, based on our extensive analysis of the Cambridge Structural Database, we believe C60(SnI4)2 is the first chiral van der Waals crystal assembled from two or more neutral components that each have Td or greater symmetry. Other chiral C60 intercalation compounds have low-symmetry intercalants, 28,29 ambiguous Flack parameters demonstrating the handedness of the structure is not determined, 30 or very high R values indicating further refinement is needed. 31 Existing C60 intercalation compounds with tetrahedral intercalants are achiral.…”