Synthesis of [60]Fullerene Hybrids Endowed with Steroids and Monosaccharides: Theoretical Underpinning as Promising anti-SARS-CoV-2 Agents.

Cyclopropanation reactions between C60 and different malonates decorated with monosaccharides and steroids using the Bingel-Hirsch methodology have allowed the obtention of a new family of hybrid compounds in good yields. A complete set of instrumental techniques has allowed us to fully characterize the hybrid derivatives and to determine the chemical structure of monocycloadducts. Besides, the proposed structures were investigated by cyclic voltammetry, which evidenced the exclusive reductive pattern of fullerene Bingel-type monoadducts. Theoretical calculations at the DFT-D3(BJ)/PBE 6-311G(d,p) level of the synthesized conjugates predict the most stable conformation and determine the factors that control the hybrid molecules' geometry. Some parameters such as polarity, lipophilicity, polar surface area, hydrophilicity index, and solvent-accessible surface area were also estimated, predicting its potential permeability and capability as cell membrane penetrators. Additionally, a molecular docking simulation has been carried out using the main protease of SARS-CoV-2 (Mpro) as the receptor, thus paving the way to study the potential application of these hybrids in biomedicine.

Safety assessment of new nanodiamonds@corrole hybrids addressed by the response of RAW-264.7 macrophages.

Safety assessment of carbon nanomaterials is of paramount importance since they are on the frontline for applications in sensing, bioimaging and drug delivery. The biocompatibility and safety of functionalized nanodiamonds (NDs) are here addressed through the study of the pro-inflammatory response of RAW-264.7 macrophages exposed to new nanodiamonds@corrole hybrids. The corrole unit selected is as a prototype for a hydrophobic organic molecule that can function as a NIR fluorophore reporter, an optical sensor, a photodynamic therapy agent or a photocatalyst. The new functional nanohybrids containing detonated nanodiamonds (NDs) were obtained through esterification using carboxylated NDs and glycol corroles. The success of the covalent functionalization via carbodiimide activation was confirmed through X-ray photoelectron spectroscopy (XPS), Raman and Fourier transform infrared (FTIR) spectroscopy. The UV-vis absorption and emission spectra of the hybrids are additive with respect to the corrole features. The cellular uptake, localization, cell viability and effects on immune cell activation of the new hybrids and of the precursors were carefully investigated using RAW-264.7 macrophages. Overall results showed that the ND@corrole hybrids had no pro-inflammatory effects on the RAW-264.7 macrophage cell line, making them an ideal candidate for a wide range of biomedical applications.

Supramolecular Assembly of Edge Functionalized Top-Down Chiral Graphene Quantum Dots.

The construction of supramolecular assemblies of heterogeneous materials at the nanoscale is an open challenge in science. Herein, new chiral graphene quantum dots (GQDs) prepared by amidation reaction introducing chiral amide groups and pyrene moieties into the periphery of GQDs are described. The analytical and spectroscopic data show an efficient chemical functionalization and the morphological study of the supramolecular ensembles using SEM and AFM microscopies reveals the presence of highly ordered fibers of several micrometers length. Fluorescence studies, using emission spectroscopy and confocal microscopy, reveal that the fibers stem from the π-π stacking of both pyrenes and GQDs, together with the hydrogen bonding interactions of the amide groups. Circular dichroism analysis supports the chiral nature of the supramolecular aggregates.

A pH-independent electrochemical aptamer-based biosensor supports quantitative, real-time measurement in vivo.

The development of biosensors capable of achieving accurate and precise molecular measurements in the living body in pH-variable biological environments (e.g. subcellular organelles, biological fluids and organs) plays a significant role in personalized medicine. Because they recapitulate the conformation-linked signaling mechanisms, electrochemical aptamer-based (E-AB) sensors are good candidates to fill this role. However, this class of sensors suffers from a lack of a stable and pH-independent redox reporter to support their utility under pH-variable conditions. Here, in response, we demonstrate the efficiency of an electron donor π-extended tetrathiafulvalene (exTTF) as an excellent candidate (due to its good electrochemical stability and no proton participation in its redox reaction) of pH-independent redox reporters. Its use has allowed improvement of E-AB sensing performance in biological fluids under different pH conditions, achieving high-frequency, real-time molecular measurements in biological samples both in vitro and in the bladders of living rats.

Assessing the Photoinduced Electron-Donating Behavior of Carbon Nanodots in Nanoconjugates.

Carbon nanodots (CNDs) undergo electron transfer in different scenarios. Previous studies have mainly focused on the electron-accepting features of CNDs in covalently linked donor-acceptor nanoconjugates. In view of this, we decided to carry out in this study the formation of covalently linked nanoconjugates that feature electron-donating pressure synthesized carbon nanodots (pCNDs) and electron-accepting 11,11,12,12-tetracyano-9,10-anthra-p-quinodimethane (TCAQ): pCND-TCAQ. The stability of the one-electron reduced form of TCAQ renders it the acceptor of choice. Detailed structural and electrochemical investigations allowed the characterization of pCND-TCAQ. Furthermore, investigations regarding intramolecular interactions, by means of steady-state and pump-probe transient absorption spectroscopies, allowed detection and characterization of three excited state species, in general, and the pCND•+-TCAQ•- charge-separated state, in particular.

Diastereoselective Synthesis of Steroid-[60]Fullerene Hybrids and Theoretical Underpinning.

The reaction of C60 with pregnen-20-carboxaldehyde, a biologically active synthetic steroid, by using a 1,3-dipolar cycloaddition reaction (Prato's protocol) results in the formation of pyrrolidine rings bearing a new stereogenic center on the C2 of the five-membered ring. The formation of the fullerene-steroid hybrids proceeds with preference for the Re face of the 1,3-dipole, with formation of a diastereomeric mixture in 73:15 ratio. The investigation of the chiroptical properties of these conjugates allowed determining the absolute configuration of the new fulleropyrrolidines. In addition, a thorough spectroscopical study permitted to determine the structure of the two mono-cycloadducts. The electrochemical properties of the new hybrids were also evaluated by cyclic voltammetry, both systems exhibit three quasi-reversible reduction waves which are cathodically shifted in regard to the parent C60. Theoretical calculations help supporting the experimental data. A conformational study combining semiempirical methods and density functional theory has predicted the most stable diastereomer. On the basis of this agreement, a possible reaction mechanism is presented. Additionally, a molecular docking simulation has been carried out using the HIV-1 protease as receptor, thus paving the way to study the possible application of these stereoisomers in biomedicine.

Mono- and Tripodal Porphyrins: Investigation on the Influence of the Number of Pyrene Anchors in Carbon Nanotube and Graphene Hybrids.

A series of molecular precursors, containing one (1 and 3) or three (2 and 4) pyrene anchors, covalently linked to porphyrins (free base or Zn), were prepared and characterized. All of them enable their π-π stacking onto low-dimensional nanocarbons including single-walled carbon nanotubes (SWCNTs) and nanographene (NG), their individualization, and their characterization. Microscopic (TEM, AFM) and spectroscopic (steady-state UV-vis and fluorescence, spectroelectrochemistry, and transient absorption measurements) techniques were at the forefront of the characterizations and were complemented by Raman spectroscopy and theoretical calculations. Of great importance is the Raman analysis, which corroborated n-doping of the nanocarbons due to the interactions with 1-4 when probed in the solid state. In solution, the situation is, however, quite different. Efficient charge separation was only observed for the graphene-based system NG/3.

Charge transfer in graphene quantum dots coupled with tetrathiafulvalenes.

Water-soluble fluorescent graphene quantum dots have been successfully prepared through a top-down approach, that is, starting with graphite, and covalently functionalizing it with π-extended tetrathiafulvalene. Charge transfer investigations reveal noticeably slower charge recombination when compared with exTTF nanoconjugates featuring carbon nanodots, for which a larger presence of trap states is observed.

Exploring Tetrathiafulvalene-Carbon Nanodot Conjugates in Charge Transfer Reactions.

Carbon nanodots (CNDs) were synthesized using low-cost and biocompatible starting materials such as citric acid/urea, under microwave irradiation, and constant pressure conditions. The obtained pressure-synthesized CNDs (pCNDs) were covalently modified with photo- and electroactive π-extended tetrathiafulvalene (exTTF) by means of a two-step esterification reaction, affording pCND-exTTF. The electronic interactions between the pCNDs and exTTF were investigated in the ground and excited states. Ultrafast pump-probe experiments assisted in corroborating that charge separation governs the deactivation of photoexcited pCND-exTTF. These size-regular structures, as revealed by AFM, are stable electron donor-acceptor conjugates of interest for a better understanding of basic processes such as artificial photosynthesis, catalysis, and photovoltaics, involving readily available fluorescent nanodots.

The Role of Planarity versus Nonplanarity in the Electronic Communication of TCAQ-Based Push-Pull Chromophores.

Donor-acceptor-substituted alkynes, endowed with 11,11,12,12-tetracyano-9,10-anthraquinodimethane (TCAQ) and N,N-dimethylaniline (DMA) units, have been further functionalized by a [2+2] cycloaddition with tetracyanoethylene (TCNE) followed by a subsequent retro-electrocyclization to form distorted nonplanar structures with bridging 1,1,4,4-tetracyanobuta-1,3-diene (TCBD) units. Comprehensive spectroscopic, electrochemical, and computational studies have been carried out to compare the electronic communication in planar (alkyne bridges) and nonplanar (TCBD bridges) TCAQ-based push-pull chromophores. Cyclic voltammetry and UV/Vis absorption measurements confirm the electronic communication between the TCAQ and DMA units despite the nonplanarity of the TCBD group. The experimental trends are strongly supported by density functional theory calculations, which further support the active electron-withdrawing role of the TCBD bridges. The novel push-pull TCAQ-based derivatives incorporating the TCBD bridge show a broad absorption in the whole visible range while the structures are highly distorted from planarity.

Heptamethine Cyanine Dyes in the Design of Photoactive Carbon Nanomaterials.

Near-infrared (NIR) absorbing nanomaterials, built from anionic heptamethine cyanine dyes and single-walled carbon nanotubes or few-layer graphene, are presented. The covalent linkage, using 1,3-dipolar cycloaddition reactions, results in nanoconjugates that synchronize the properties of both materials, as demonstrated by an in-depth characterization study carried out by transmission electron microscopy, atomic force microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. UV-vis-NIR and Raman spectroscopies further confirmed the unique electronic structure of the novel photoactive nanomaterials.

Single-molecule conductance of a chemically modified, π-extended tetrathiafulvalene and its charge-transfer complex with F4TCNQ.

We describe the synthesis and single-molecule electrical transport properties of a molecular wire containing a π-extended tetrathiafulvalene (exTTF) group and its charge-transfer complex with F4TCNQ. We form single-molecule junctions using the in situ break junction technique using a homebuilt scanning tunneling microscope with a range of conductance between 10 G0 down to 10(-7) G0. Within this range we do not observe a clear conductance signature of the neutral parent molecule, suggesting either that its conductance is too low or that it does not form a stable junction. Conversely, we do find a clear conductance signature in the experiments carried out on the charge-transfer complex. Due to the fact we expected this species to have a higher conductance than the neutral molecule, we believe this supports the idea that the conductance of the neutral molecule is very low, below our measurement sensitivity. This idea is further supported by theoretical calculations. To the best of our knowledge, these are the first reported single-molecule conductance measurements on a molecular charge-transfer species.

Thermodynamically stable [4 + 2] cycloadducts of lanthanum-encapsulated endohedral metallofullerenes.

The [4 + 2] cycloaddition of o-quinodimethanes, generated in situ from the sultine 4,5-benzo-3,6-dihydro-1,2-oxathiin 2-oxide and its derivative, to La metal-encapsulated fullerenes, La2@C80 or La@C82, afforded the novel derivatives of endohedral metallofullerenes (3a,b, 4a,b and 5b). Molecular structures of the resulting compounds were elucidated using spectroscopic methods such as MALDI-TOF mass, optical absorption, and NMR spectroscopy. The [4 + 2] adducts of La2@C80 (3a,b, and 4a,b) and La@C82 (5b), respectively, retain diamagnetic and paramagnetic properties, as confirmed by EPR spectroscopy. Dynamic NMR measurements of 4a at various temperatures demonstrated the boat-to-boat inversions of the addend. In addition, 5b revealed remarkable thermal stability in comparison with the reported [4 + 2] cycloadduct of pentamethylcyclopentadiene and La@C82 (6). These findings demonstrate the utility of sultines to afford thermodynamically stable endohedral metallofullerene derivatives for the use in material science.

Charge transfer-assisted self-limited decyanation reaction of TCNQ-type electron acceptors on Cu(100).

TCNQ derivatives adsorbed on a metal surface undergo a self-limited decyanation reaction that only affects two out of the four cyano groups in the molecule. Combined Scanning Tunneling Microscopy/X-ray Photoelectron Spectroscopy experiments and Density Functional Theory calculations relate the self-limiting behavior to the transfer of electrons from the metal to the molecule.

Rates and energetics of intramolecular electron transfer processes in conjugated metallofullerenes.

In this paper, we report on the design, redox potentials, excited state energies and radical ion pair state energies in electron donor-acceptor conjugates comprising the electron-donating π-extended tetrathiafulvalene and several electron-accepting fullerenes. To this end, we contrast an empty fullerene, that is, C60, with two endohedral metallofullerenes, that is, open-shell La@C82 and closed-shell La2@C80, in terms of charge separation and charge recombination dynamics.

The chemistry of pristine graphene.

Graphene is a unique material with outstanding mechanical and electronic properties. For solution processes graphene layers have to be stabilized by means of molecular or supramolecular chemical derivatization, prior to their transfer to solid substrates. The most common chemical methodology for the preparation of graphene involves the formation of graphene oxide under highly oxidizing conditions, which even after reduction, lacks the electronic quality of pristine graphene. Presently, there is increasing concern in the chemical community about the starting material quality, and recent efforts are directed to wet chemical approaches toward high-quality graphene flakes which encompass the use of graphite as initial material. In addition, epitaxial growth of graphene on metallic surfaces is becoming a powerful technique for the production of pristine graphene with a control on its electronic properties, somehow due to the supramolecular interaction with the metallic surface. Current approaches for the preparation of modified pristine graphene are the aim of this review.

Stability of single- and few-molecule junctions of conjugated diamines.

We study the stability of molecular junctions based on an oligo(phenylenethynylene) (OPE) diamine using a scanning tunneling microscope at room temperature. In our analysis, we were able to differentiate between junctions most probably formed by either one or several molecules. Varying the stretching rate of the junctions between 0.1 and 100 nm/s, we observe practically no variation of the length over which both kinds of junction can be stretched before rupture. This is in contrast with previously reported results for similar compounds. Our results suggest that, over the studied speed range, the junction breakage is caused purely by the growth of the gap between the gold electrodes and the elastic limit of the amine-gold bond. On the other hand, without stretching, junctions would survive for periods of time longer than our maximum measurement time (at least 10 s for multiple-molecule junctions) and can be considered, hence, very stable.

An endohedral metallofullerene as a pure electron donor: intramolecular electron transfer in donor-acceptor conjugates of La2@C80 and 11,11,12,12-tetracyano-9,10-anthra-p-quinodimethane (TCAQ).

An endohedral metallofullerene, La(2)@C(80), is covalently linked to the strong electron acceptor 11,11,12,12-tetracyano-9,10-anthra-p-quinodimethane (TCAQ) by means of the Prato reaction, affording two different [5,6]-metallofulleropyrrolidines, namely 1a and 2a. 1a and 2a were isolated and fully characterized by means of MALDI-TOF mass, UV-vis-NIR absorption, and NMR spectroscopies. In addition, cyclic voltammetry (CV) and differential pulse voltammetry (DPV) corroborated the unique redox character of 2a, that is, the presence of the electron-donating La(2)@C(80) and the electron-accepting TCAQ. Although a weak electronic coupling dictates the interactions between La(2)@C(80) and TCAQ in the ground state, time-resolved transient absorption experiments reveal that in the excited state (i.e., π-π* centered at La(2)@C(80)) the unprecedented formation of the (La(2)@C(80))(•+)-(TCAQ)(•-) radical ion pair state evolves in nonpolar and polar media with a quantum efficiency of 33%.

Stabilizing ion and radical ion pair states in a paramagnetic endohedral metallofullerene/π-extended tetrathiafulvalene conjugate.

Electron donor-acceptor conjugates of paramagnetic endohedral metallofullerenes and π-extended tetrathiafulvalene (exTTF) were synthesized, characterized, and probed with respect to intramolecular electron transfer involving paramagnetic fullerenes. UV-vis-NIR absorption spectroscopy complemented by electrochemical measurements attested to weak electronic interactions between the electron donor, exTTF, and the electron acceptor, La@C(82), in the ground state. In the excited state, photoexcitation powers a fast intramolecular electron transfer to yield an ion and radical ion pair state consisting of one-electron-reduced La@C(82) and of one-electron-oxidized exTTF.

Tetrathiafulvalene-based nanotweezers-noncovalent binding of carbon nanotubes in aqueous media with charge transfer implications.

Electron donor-acceptor hybrids based on single wall carbon nanotubes (SWCNT) are one of the most promising functional structures that are currently developed in the emerging areas of energy conversion schemes and molecular electronics. As a suitable electron donor, π-extended tetrathiafulvalene (exTTF) stands out owing to its recognition of SWCNT through π-π stacking and electron donor-acceptor interactions. Herein, we explore the shape and electronic complementarity between different types of carbon nanotubes (CNT) and a tweezers-shaped molecule endowed with two exTTFs in water. The efficient electronic communication between semiconducting SWCNT/multiwall carbon nanotubes (MWCNT), on one hand, and the water-soluble exTTF nanotweezers 8, on the other hand, has been demonstrated in the ground and excited state by using steady-state as well as time-resolved spectroscopies, which were further complemented by microscopy. Importantly, appreciable electronic communication results in the electronic ground state having a shift of electron density, that is, from exTTFs to CNT, and in the electronic excited state having a full separation of electron density, that is oxidized exTTF and reduced CNT. Lifetimes in the range of several hundred picoseconds, which were observed for the corresponding electron transfer products upon light irradiation, tend to be appreciably longer in MWCNT/8 than in SWCNT/8.