Roberto Milani

The Halogen Bond

The halogen bond occurs when there is evidence of a net attractive interaction between an electrophilic region associated with a halogen atom in a molecular entity and a nucleophilic region in another, or the same, molecular entity. In this fairly extensive review, after a brief history of the interaction, we will provide the reader with a snapshot of where the research on the halogen bond is now, and, perhaps, where it is going. The specific advantages brought up by a design based on the use of the halogen bond will be demonstrated in quite different fields spanning from material sciences to biomolecular recognition and drug design.

Supramolecular amplification of amyloid self-assembly by iodination

Amyloid supramolecular assemblies have found widespread exploitation as ordered nanomaterials in a range of applications from materials science to biotechnology. New strategies are, however, required for understanding and promoting mature fibril formation from simple monomer motifs through easy and scalable processes. Noncovalent interactions are key to forming and holding the amyloid structure together. On the other hand, the halogen bond has never been used purposefully to achieve control over amyloid self-assembly. Here we show that single atom replacement of hydrogen with iodine, a halogen-bond donor, in the human calcitonin-derived amyloidogenic fragment DFNKF results in a super-gelator peptide, which forms a strong and shape-persistent hydrogel at 30-fold lower concentration than the wild-type pentapeptide. This is remarkable for such a modest perturbation in structure. Iodination of aromatic amino acids may thus develop as a general strategy for the design of new hydrogels from unprotected peptides and without using organic solvents.

Halogen-bonded mesogens direct polymer self-assemblies up to millimetre length scale

Aligning polymeric nanostructures up to macroscale in facile ways remains a challenge in materials science and technology. Here we show polymeric self-assemblies where nanoscale organization guides the macroscopic alignment up to millimetre scale. The concept is shown by halogen bonding mesogenic 1-iodoperfluoroalkanes to a star-shaped ethyleneglycol-based polymer, having chloride end-groups. The mesogens segregate and stack parallel into aligned domains. This leads to layers at ~10 nm periodicity. Combination of directionality of halogen bonding, mesogen parallel stacking and minimization of interfacial curvature translates into an overall alignment in bulk and films up to millimetre scale. Upon heating, novel supramolecular halogen-bonded polymeric liquid crystallinity is also shown. As many polymers present sites capable of receiving halogen bonding, we suggest generic potential of this strategy for aligning polymer self-assemblies.

Surface modification of poly(ethylene-co-acrylic acid) with amino-functionalized silica nanoparticles

In this work we studied the possibility to achieve a hybrid-surface through the modification, via a facile wet chemical process, of the surface of films of poly(ethylene-co-acrylic acid) (EAA) with amino-modified silica nanoparticles. Films of EAA were preliminarily activated by the introduction of –COCl groups on their surface. Silica nanoparticles were thereafter covalently bound on the polymeric surface as confirmed by FTIR, ATR-FTIR, XPS, NMR and SEM determinations. The nanoparticles formed a multilayer on the film surface and covered almost uniformly the whole film surface. Direct measurements of superficial amino groups by titration allowed us to detect a concentration of about 18 nmol cm−2. The presence of this uniform layer of nanoparticles bearing polar groups strongly changed the wettability of the material as confirmed by static contact angle measurements that passed from 87° of the neat EAA to about 30° of the amino-functionalized silica nanoparticles modified material.

Surface functionalization with phosphazene substrates. Part I: Silica and Si-(100) surface functionalization with cyclophosphazenes partially substitued with trialkoxysilane derivatives and 4-cyanophenol as a marker molecule

In this paper we report the utilization of phosphazene substrates for the surface functionalization of silicon-based materials (e.g., silica gel beads and crystalline silicon(100) wafers) and for the preparation of monoliths by means of a sol-gel technique. We used multifunctional cyclophosphazenes to prepare trimers substituted with equimolecular amounts of γ-aminopropyltriethoxysilane and 4-cyanophenol. The first substituent was used to attach the phosphazene materials to the surface of the silicon-based substrates by reaction of the triethoxysilane functions with the free hydroxylic groups present on the surface of the silica gel particles or of the crystalline silicon wafers. Furthermore, the second substituent, i.e., 4-cyanophenol, was exploited as an internal marker, because of the presence of a peculiar band at 2230 cm−1 in its IR spectrum, to reveal the presence of the cyclophosphazene on the surface of the functionalized substrates. This approach is completely general and can be used very easily to induce specific modifications on the surface of different materials by carefully selecting the substituent groups inserted in the cyclophosphazene substrate.

Hierarchical Self-Assembly of Halogen-Bonded Block Copolymer Complexes into Upright Cylindrical Domains

Summary Self-assembly of block copolymers into well-defined, ordered arrangements of chemically distinct domains is a reliable strategy for preparing tailored nanostructures. Microphase separation results from the system, minimizing repulsive interactions between dissimilar blocks and maximizing attractive interactions between similar blocks. Supramolecular methods have also achieved this separation by introducing small-molecule additives binding specifically to one block by noncovalent interactions. Here, we use halogen bonding as a supramolecular tool that directs the hierarchical self-assembly of low-molecular-weight perfluorinated molecules and diblock copolymers. Microphase separation results in a lamellar-within-cylindrical arrangement and promotes upright cylindrical alignment in films upon rapid casting and without further annealing. Such cylindrical domains with internal lamellar self-assemblies can be cleaved by solvent treatment of bulk films, resulting in separated and segmented cylindrical micelles stabilized by halogen-bond-based supramolecular crosslinks. These features, alongside the reversible nature of halogen bonding, provide a robust modular approach for nanofabrication.

Design of Highly Stable Echogenic Microbubbles through Controlled Assembly of Their Hydrophobin Shell

Dispersing hydrophobin HFBII under air saturated with perfluorohexane gas limits HFBII aggregation to nanometer-sizes. Critical basic findings include an unusual co-adsorption effect caused by the fluorocarbon gas, a strong acceleration of HFBII adsorption at the air/water interface, the incorporation of perfluorohexane into the interfacial film, the suppression of the fluid-to-solid 2D phase transition exhibited by HFBII monolayers under air, and a drastic change in film elasticity of both Gibbs and Langmuir films. As a result, perfluorohexane allows the formation of homogenous populations of spherical, narrowly dispersed, exceptionally stable, and echogenic microbubbles.

Atomistic simulation of hydrophobin HFBII conformation in aqueous and fluorous media and at the water/vacuum interface.

Hydrophobins are proteins of interest for numerous applications thanks to their unique conformational and surface properties and their ability to self-assemble at interfaces. Here we report fully atomistic molecular mechanics and molecular dynamics results together with circular dichroism experimental data, aimed to study the conformational properties of the hydrophobin HFBII in a fluorinated solvent in comparison with a water solution and/or at an aqueous/vacuum interface. Both the atomistic simulations and the circular dichroism data show the remarkable structural stability of HFBII at all scales in all these environments, with no significant structural change, although a small cavity is formed in the fluorinated solvent. The combination of theoretical calculations and circular dichroism data can describe in detail the protein conformation and flexibility in different solvents and/or at an interface, and constitutes a first step towards the study of their self-assembly.

Surface functionalization with phosphazene substrates, Part IV: Silica and Si(100) surface functionalization using cyclophosphazenes partially substituted with trialkoxysilane derivatives and PEG-750 monomethylether, 2,2,3,3-tetrafluoropropanol and 4-hydroxyazobenzene

This paper deals with the possibility of functionalizing the surface of silicon-based materials by exploiting cyclophosphazenes containing suitable substituent groups. Thus, phosphazene trimers were prepared, containing about 50% of the reactive sites substituted by γ-aminopropyltriethoxy silane (APTES), while the residual positions in the cycle contain poly(ethylene glycol) monomethylether (MW approx. 750; PEG-750-ME), tetrafluoropropanol (TFP) and 4-hydroxyazobenzene (AzB). Using these novel materials we succeeded in surface functionalizing SiO2 beads in the coating of silicon wafers or sodalime slides and in the preparation of cyclophosphazene-based monoliths in the presence of hydrolyzed TEOS by sol–gel technique. The whole series of products has been characterized by standard spectroscopic (IR, UV-Vis, 1H-, 13C-, 29Si- and 31P-NMR, both in solution and in solid state) and thermal (DSC and DMTA) techniques. This approach to the surface functionalization of silicon-based materials containing carefully selected substituents is completely general and can be used to attach to the hydroxylated surfaces practically any type of nucleophile that can be supported on the cyclophosphazene ring.

Oxazoline-Containing Phosphazene Derivatives, Part III: Synthesis and Characterization of Novel Cyclophosphazenes Functionalized With Chiral 2-Oxazoline Groups

In this paper we describe the synthesis and the characterization of a series of cyclophosphazenes substituted with 2-oxazoline-containing moieties, with and without optical activity. These products could be obtained by reacting cyclophosphazenes containing six (hexachlorocyclophosphazene, C-6-Cl), two (2,2-dichloro-4,4,6,6-bis[spiro(2′,2″-dioxy–1′,1″-biphenyl)]cyclophosphazene, C-2-Cl) and one (pentakis(phenoxy)monochlorocyclophosphazene, C-1-Cl) chlorine atoms, respectively, with a series of 4-hydroxyphenyl-2-oxazolines, as obtained by condensation reaction of methyl-4-hydroxybenzoate with 2-aminoethanol and with chiral and racemic 1-amino-2-propanol, and successive cyclization reactions of the resulting hydroxyamides to 2-oxazoline compounds.