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.

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.

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.

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.

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.

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.

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.

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.

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.

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%.

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.

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.

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.

Donor-acceptor conjugates of lanthanum endohedral metallofullerene and pi-extended tetrathiafulvalene.

Stable donor-acceptor conjugates (2, 3) involving an endohedral metallofullerene, La(2)@I(h)-C(80), and pi-extended tetrathiafulvalene (exTTF) have been synthesized by highly regioselective 1,3-dipolar cycloadditions of exTTF-containing azomethine ylides to the endofullerene, yielding exclusively [5,6] metallofulleropyrrolidines with C(1) symmetry in high yields (68-77%). The cyclic voltammograms (CVs) of the conjugates reveal the redox active character of the system due to the presence of both donor and acceptor groups, that is, exTTF and La(2)@I(h)-C(80), respectively. Furthermore, the electrochemically reversible character of the endofullerene confirms the presence of the [5,6] adduct. Despite the relatively close proximity between the exTTF and the endohedral metallofullerene (EMF), only a weak electronic interaction was observed in the ground state, as evidenced by absorption spectroscopy and CV measurements of 2 and 3. On the other hand, in the excited state the fast formation of a radical ion-pair state (i.e., 6.0 x 10(10) s(-1)), that is, the reduction of the electron accepting La(2)@C(80) and the oxidation of exTTF, evolves with lifetimes as long as several ns (3.0 x 10(8) s(-1)) in toluene. Transient absorption spectroscopy experiments confirmed these observations.

A molecular Ce2@I(h)-C80 switch--unprecedented oxidative pathway in photoinduced charge transfer reactivity.

We report for the first time the versatile Ce(2)@I(h)-C(80) building block toward synthesizing a novel electron donor-acceptor conjugate, Ce(2)@I(h)-C(80)-ZnP (1). A systematic investigation of the charge transfer chemistry documents a reductive charge transfer (i.e., formation of (Ce(2)@I(h)-C(80))(*-)-(ZnP)(*+)) in nonpolar media (i.e., toluene/THF), while an oxidative charge transfer (i.e., formation of (Ce(2)@I(h)-C(80))(*+)-(ZnP)(*-)) dominates in polar media (i.e., benzonitrile/DMF). Reduction of the [Ce(2)](6+) cluster, which is highly localized and collinearly arranged with respect to the quaternary bridge carbon, is sufficiently exothermic in all solvents. Notably weak is the electronic coupling between the [Ce(2)](6+) cluster and the electron-donating ZnP. The oxidation of C(80)(6-) and the simultaneous reduction of ZnP, on the other hand, necessitate solvent stabilization. In such a case, the strongly exothermic (Ce(2)@I(h)-C(80))(*-)-(ZnP)(*+) radical ion pair state formation is compensated within the framework of a nonadiabatic charge transfer by a C(80)(6-)/ZnP electronic matrix element, as the sum of good overlap and short distance, that exceeds that for [Ce(2)](6+)/ZnP.

Lanthanide(III) bis(phthalocyaninato)-[60]fullerene dyads: synthesis, characterization, and photophysical properties.

A novel series of double-decker lanthanide(III) bis(phthalocyaninato)-C(60) dyads [Ln(III)(Pc)(Pc')]-C(60) (M=Sm, Eu, Lu; Pc=phthalocyanine) (1 a-c) have been synthesized from unsymmetrically functionalized heteroleptic sandwich complexes [Ln(III)(Pc)(Pc')] (Ln=Sm, Eu, Lu) 3 a-c and fulleropyrrolidine carboxylic acid 2. The sandwich complexes 3 a-c were obtained by means of a stepwise procedure from unsymmetrically substituted free-base phthalocyanine 5, which was first transformed into the monophthalocyaninato intermediate [Ln(III)(acac)(Pc)] and further reacted with 1,2-dicyanobenzene in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). (1)H NMR spectra of the bis(phthalocyaninato) complexes 3 a-c and dyads 1 a-c were obtained by adding hydrazine hydrate to solutions of the complexes in [D(7)]DMF, a treatment that converts the free radical double-deckers into the protonated species, that is, [Ln(III)(Pc)(Pc')H] and [Ln(III)(Pc)(Pc')H]-C(60). The electronic absorption spectra of 3 a-c and 1 a-c in THF exhibit typical transitions of free-radical sandwich complexes. In the case of dyads 1 a-c, the spectra display the absorption bands of both constituents, but no evidence of ground-state interactions could be appreciated. When the UV/Vis spectra of 3 a-c and 1 a-c were recorded in DMF, typical features of the reduced forms were observed. Cyclic voltammetry studies for 3 a-c and 1 a-c were performed in THF. The electrochemical behavior of dyads 1 a-c is almost the exact sum of the behavior of the components, namely the double-decker [Ln(III)(Pc)(Pc')] and the C(60) fullerene, thus confirming the lack of ground-state interactions between the electroactive units. Photophysical studies on dyads 1 a-c indicate that only after irradiation at 387 nm, which excites both C(60) and [Ln(III)(Pc)(Pc')] components, a photoinduced electron transfer from the [Ln(III)(Pc)(Pc')] to C(60) occurs.

Electron donor-acceptor interactions in regioselectively synthesized exTTF(2)-C(70)(CF(3))(10) dyads.

The decakis(trifluoromethyl)fullerene C(1)-C(70)(CF(3))(10), in which the CF(3) groups are arranged on a para(7)-meta-para ribbon of C(6)(CF(3))(2) edge-sharing hexagons, and which has now been prepared in quantities of hundreds of milligrams, was reacted under standard Bingel-Hirsch conditions with a bis-pi-extended tetrathiafulvalene (exTTF) malonate derivative to afford a single exTTF(2)-C(70)(CF(3))(10) regioisomer in 80 % yield based on consumed starting material. The highly soluble hybrid was thoroughly characterized by using 1D (1)H, (13)C, and (19)F NMR, 2D NMR, and UV/Vis spectroscopy; matrix-assisted laser desorption ionization (MALDI) mass spectrometry; and electrochemistry. The cyclic voltammogram of the exTTF(2)-C(70)(CF(3))(10) dyad revealed an irreversible second reduction process, which is indicative of a typical retro-Bingel reaction; whereas the usual phenomenon of exTTF inverted potentials (E1ox>E2ox), resulting in a single, two-electron oxidation process, was also observed. Steady-state and time-resolved photolytic techniques demonstrated that the C(1)-C(70)(CF(3))(10) singlet excited state is subject to a rapid electron-transfer quenching. The resulting charge-separated states were identified by transient absorption spectroscopy, and radical pair lifetimes of the order of 300 ps in toluene were determined. The exTTF(2)-C(70)(CF(3))(10) dyad represents the first example of exploitation of the highly soluble trifluoromethylated fullerenes for the construction of systems able to mimic the photosynthetic process, and is therefore of interest in the search for new materials for photovoltaic applications.

Efficient regioselective [4+2] cycloaddition of o-quinodimethane to C(70)(CF(3))(10).

The Diels-Alder reaction of C(1)-C(70)(CF(3))(10) and 3,6-dimethoxy-1,2-quinodimethane leads regioselectively to the formation of a new cycloadduct that has been fully characterized by spectroscopic and electrochemical methods as well as by X-ray diffraction.

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.