Stereospecific Self-Assembly Processes of Porphyrin-Proline Conjugates: From the Effect of Structural Features and Bulk Solvent Properties to the Application in Stereoselective Sensor Systems

Abstract

Conjugating the porphyrin ring with an amino acid via amide linkage represents a straightforward way for conferring both amphiphilicity and chirality to the macrocycle. Proline residue is a good choice in this context since its conformational rigidity allows for porphyrin assembling where molecular chirality is efficiently transferred and amplified using properly honed aqueous environments. Herein, we describe the evolution of the studies carried out by our group to achieve chiral systems from some porphyrin-proline derivatives, both in solution and in the solid state. The discussion focuses on some fundamental aspects reflecting on the final molecular architectures obtained, which are related to the nature of the appended group (stereochemistry and charge), the presence of a metal ion coordinated to the porphyrin core and the bulk solvent properties. Indeed, fine-tuning the mentioned parameters enables the achievement of stereospecific structures with distinctive chiroptical and morphological features. Solid films based on these chiral systems were also obtained and their recognition abilities in gaseous and liquid phase are here described.

Keywords: chirality; porphyrins; proline; sensors; supramolecular chemistry.

Scheme 1

Molecular structures of the porphyrin-proline conjugates herein discussed. The main modifiable molecular synthons on the macrocycles resulting in a distinctive aggregation behaviour are highlighted.

Scheme 2

Preparation of the chiral porphyrin derivatives described in this work. (A) (i) EDCl, HOBT, dry THF/CH₂Cl₂, 0 °C, 1 h, then RT 48 h. (ii) CH₃I, DMF, RT, 72 h. (iii) NaCl/CH₃OH, RT, overnight. (iv) M(OAc)₂, CHCl₃/CH₃OH (5/1, v/v), RT, 1 h. (B) (i) EDCl, HOBT, dry CH₂Cl₂, 0 °C, 1 h, then RT 48 h. (ii) TFA/CH₂Cl₂ (2/3, v/v), 1.5 h. (iii) Aqueous NaHCO₃, then Na₂SO₄. (iv) Zn(OAc)₂, CHCl₃/CH₃OH (5/1, v/v), RT, 1 h.

Scheme 3

Idealised cartoon of the limiting molecular morphologies of H (left) and J (right) porphyrin aggregates.

Figure 1

(a) UV-Visible spectra of the aggregates of H₂P(L)Pro(+) in different hydroalcoholic media; the spectrum in non-aggregative conditions (pure ethanol) is reported for comparison. (b) Comparison of the CD spectra of the aggregates obtained from different water-containing solvent mixtures. Adapted from [41], with permission from the Royal Society of Chemistry, Copyright © 2005.

Figure 2

(a) Kinetic profile (UV-Vis intensity variation of Soret band) of H₂P(L)Pro(–) in EtOH/H₂O 25/75 v:v. The inset reports the corresponding profile for the H₂P(L)Pro(+) counterpart. (b) Comparison of the CD profiles of the porphyrin-free base derivatives. Adapted from [43], with permission from Wiley-VCH, Copyright © 2010, and from [41], with permission from the Royal Society of Chemistry, Copyright © 2005.

Figure 3

AFM images of porphyrin aggregates layered onto HOPG, formed in EtOH/H₂O 25/75 v:v. (a) H₂P(L)Pro(−); (b) H₂P(L)Pro(+). Adapted from [43], with permission from Wiley-VCH, Copyright © 2010.

Figure 4

(a) Kinetic course for the aggregation of CuP(L)Pro(+) showing the occurrence of an initial burst followed by a slow autocatalytic step. The initial point (t₀) is calculated in non-aggregative conditions (50 % hydroalcoholic medium). (b) CD plot for the aggregates of ZnP(L)Pro(+); in the inset is reported the analogous spectrum for the CuP(L)Pro(+) derivative. Adapted from [69], with permission from the Royal Society of Chemistry, Copyright © 2019.

Figure 5

Aggregation of ZnP(L)Pro(−) and ZnP(D)Pro(−) (5 μM; EtOH/H₂O 25/75 v:v). (a) CD plot at the initial (t = 0) stage; (b) CD plot at equilibrium. (c) Autocatalytic kinetic profile for the second stage of the aggregation of the (L)-derivative. The points represent the variation of the CD bands vs. time at the given wavelength. Adapted from OPEN ACCESS [44].

Figure 6

(a) CD spectra of ZnP(D)Pro(−) aggregates (5 μM; EtOH/H₂O 25/75 v:v) in the presence of (R)-phenylethylamine (dotted line) and (S)-phenylethylamine (continuous line). SEM images of ZnP(L)Pro(−) aggregates (10 μM; EtOH/H₂O 25/75 v:v) in the presence of (R)-phenylethylamine (1 mM) (b) and without added nitrogen ligand (c). Adapted from OPEN ACCESS [73].

Figure 7

(a) CD spectrum of a spontaneously deposited layer of H₂P(L)Pro(+) aggregates from EtOH/H₂O 25/75 v:v. (b) CD spectra of LB films of H₂P(L)Pro(+) deposited on quartz in an increasing number of layers (blue trace, monolayer; red trace, 5 layers; green trace, 7 layers). Adapted from [42] and from [79] with permission from the World Scientific, Copyright © 2011 and © 2019, respectively.

Figure 8

(a) TEM images of pyramidal ZnO nanoparticles capped by a layer of ZnP(L)Pro(−) aggregates (artificially shown as a pink colour). (b) CD spectra of drop-casted material; black-trace, bare ZnO nanoparticles; red-trace, ZnO nanoparticles-porphyrin aggregates conjugates, evidencing the induced chiral feature of the zinc oxide surface (ca 375 nm). (c) Dynamic response of a QMB device with a layer of ZnO nanoparticles-porphyrin aggregates conjugates upon exposure to vapours of (R)-limonene (red-trace) and (S)-limonene (black-trace). (d) Plot of QMB responses at the different dilutions of the saturated vapour pressure of (R)-limonene (red trace) and (S)-limonene (black trace). Adapted with permission from [39], Copyright © 2019, American Chemical Society.

Figure 9

(a) Fluorescence quenching of H₂P(L)Pro(−) LS film in the presence upon exposure to aqueous solutions of (L)-proline at increasing concentrations. (b) Quenching of fluorescence of H₂P(L)Pro(−) LS film in the presence of (L)-proline (black dots) and (D)-proline (red dots). Adapted from OPEN ACCESS [40].