Marika Savarese

Fluorescence Lifetimes and Quantum Yields of Rhodamine Derivatives: New Insights from Theory and Experiment

Although lifetimes and quantum yields of widely used fluorophores are often largely characterized, a systematic approach providing a rationale of their photophysical behavior on a quantitative basis is still a challenging goal. Here we combine methods rooted in the time-dependent density functional theory and fluorescence lifetime imaging microscopy to accurately determine and analyze fluorescence signatures (lifetime, quantum yield, and band peaks) of several commonly used rhodamine and pyronin dyes. We show that the radiative lifetime of rhodamines can be correlated to the charge transfer from the phenyl toward the xanthene moiety occurring upon the S(0) ← S(1) de-excitation, and to the xanthene/phenyl relative orientation assumed in the S(1) minimum structure, which in turn is variable upon the amino and the phenyl substituents. These findings encourage the synergy of experiment and theory as unique tool to design finely tuned fluorescent probes, such those conceived for modern optical sensors.

Exploring the Metric of Excited State Proton Transfer Reactions

The excited state proton transfer (ESPT) reaction taking place between 7-hydroxy-4-(trifluorometyl)coumarin and 1-methylimidazole, recently experimentally characterized, has been here considered as a case study to illustrate the possibility of using theoretical approaches rooted in density functional theory (DFT) and time-dependent DFT (TD-DFT) for the description of complex reactions occurring at the excited state. In particular, beside identifying all stable species occurring at the ground and excited state during the ESPT reaction, a quantitative characterization of their photophysical properties, such as absorption and emission, is obtained by properly including solvent effects. More interestingly, a computational protocol enabling one to locate possible reaction pathways for the ESPT is here proposed. This protocol is based on the use of density based indices purposely developed to characterize the properties of vertical and relaxed excited states which allow one to discriminate the most favorable reaction paths on potential energy surfaces that are in the case of ESPT intrinsically very flat and difficult to characterize based on sole energy criteria, thus opening a new scenario for the description of photoinduced proton transfer reactions.

Describing Excited State Intramolecular Proton Transfer in Dual Emissive Systems: A Density Functional Theory Based Analysis

The excited state intramolecular proton transfer (ESIPT) reaction taking place within 2-(2-hydroxyphenyl)benzoxazole (HBT) and two recently experimentally characterized napthalimide derivatives-known as N-1 and N-4-has been investigated in order to identify and test a possible protocol for the description and complete mechanistic and electronic characterization of the reaction at the excited state. This protocol is based on density functional theory, time-dependent density functional theory, and a recently proposed electron density based index (DCT). This method is able to identify all stable species involved in the reaction, discriminate between possible reaction pathways over potential energy surfaces (PES), which are intrinsically very flat and difficult to characterize, and quantitatively measure the excited state charge transfer character throughout the reaction. The photophysical properties of the molecules (i.e., absorption and emission wavelength) are also quantitatively determined via the implicit inclusion of solvent effects in the case of toluene and, the more polar, tetrahydrofuran. The accuracy obtained with this protocol then opens up the possibility of the ab initio design of molecules exhibiting ESIPT for tailored applications such as highly selective molecular sensors.

Studies on the Enantioselective Iminium Ion Trapping of Radicals Triggered by an Electron-Relay Mechanism

A combination of electrochemical, spectroscopic, computational, and kinetic studies has been used to elucidate the key mechanistic aspects of the previously reported enantioselective iminium ion trapping of photochemically generated carbon-centered radicals. The process, which provides a direct way to forge quaternary stereocenters with high fidelity, relies on the interplay of two distinct catalytic cycles: the aminocatalytic electron-relay system, which triggers the stereoselective radical trap upon iminium ion formation, and the photoredox cycle, which generates radicals under mild conditions. Critical to reaction development was the use of a chiral amine catalyst, bearing a redox-active carbazole unit, which could rapidly reduce the highly reactive and unstable intermediate generated upon radical interception. The carbazole unit, however, is also involved in another step of the electron-relay mechanism: the transiently generated carbazole radical cation acts as an oxidant to return the photocatalyst into the original state. By means of kinetic and spectroscopic studies, we have identified the last redox event as being the turnover-limiting step of the overall process. This mechanistic framework is corroborated by the linear correlation between the reaction rate and the reduction potential of the carbazole unit tethered to the aminocatalyst. The redox properties of the carbazole unit can thus be rationally tuned to improve catalytic activity. This knowledge may open a path for the mechanistically driven design of the next generation of electron-relay catalysts.

Intrinsic and dynamical reaction pathways of an excited state proton transfer.

The detailed knowledge of excited state proton transfer mechanisms in complex environments is of paramount importance in chemistry. However, the definition of an effective reaction coordinate and the understanding of the driving force of the reaction can be difficult from both the experimental and the theoretical points of view. Here we analyzed by theoretical approaches the mechanism and the driving forces of the excited state proton transfer reaction occurring between the 7-hydroxy-4-(trifluoromethyl)coumarin photoacid and the 1-methylimidazole base molecules in toluene solution. In particular, we compared the intrinsic and the dynamical reaction pathways, obtained by integrating the reaction coordinate, and by performing ab initio simulations of molecular dynamics, respectively. Time-dependent density functional theory and polarizable solvation continuum models were adopted to define the excited state potential energy surface. Results were analyzed by means of the D(CT) electronic density based index. Our findings suggest that the reaction coordinate is mainly composed of several intra- and intermolecular modes of the reactants. An analysis of both the intrinsic coordinate and the dynamical results shows that the charge transfer induced by electronic excitation of the coumarin molecule is the main proton transfer driving force. With regards to the methodological validation, the combination of ab initio molecular dynamics with time-dependent density functional theory appears to be feasible and reliable to study excited state proton transfer reactions in the condensed phase.

Integration of binding peptide selection and multifunctional particles as tool-box for capture of soluble proteins in serum

In this paper, we report on a general approach for the detection of a specific tumoural biomarker directly in serum. Such detection is made possible using a protein-binding peptide selected through an improved phage display technique and then conjugated to engineered microparticles (MPs). Protein biomarkers represent an unlimited source of information for non-invasive diagnostic and prognostic tests; MP-based assays are becoming largely used in manipulation of soluble biomarkers, but their direct use in serum is hampered by the complex biomolecular environment. Our technique overcomes the current limitations as it produces a selective MP—engineered with an antifouling layer—that ‘captures’ the relevant protein staying impervious to the background. Our system succeeds in fishing-out the human tumour necrosis factor alpha directly in serum with a high selectivity degree. Our method could have great impact in soluble protein manipulation and detection for a wide variety of diagnostic applications.

Importance of Orbital Optimization for Double-Hybrid Density Functionals: Application of the OO-PBE-QIDH Model for Closed- and Open-Shell Systems

We assess here the reliability of orbital optimization for modern double-hybrid density functionals such as the parameter-free PBE-QIDH model. We select for that purpose a set of closed- and open-shell strongly and weakly bound systems, including some standard and widely used data sets, to show that orbital optimization improves the results with respect to standard models, notably for electronically complicated systems, and through first-order properties obtained as derivatives of the energy.

Quadratic integrand double-hybrid made spin-component-scaled

We propose two analytical expressions aiming to rationalize the spin-component-scaled (SCS) and spin-opposite-scaled (SOS) schemes for double-hybrid exchange-correlation density-functionals. Their performances are extensively tested within the framework of the nonempirical quadratic integrand double-hybrid (QIDH) model on energetic properties included into the very large GMTKN30 benchmark database, and on structural properties of semirigid medium-sized organic compounds. The SOS variant is revealed as a less computationally demanding alternative to reach the accuracy of the original QIDH model without losing any theoretical background.

Computational Insights into Excited‐State Proton‐Transfer Reactions in Azo and Azomethine Dyes

State of the art density functional theory approaches are employed to provide an accurate description of the photophysical properties of azodyes and Schiff bases displaying intramolecular hydrogen-bonding features. These compounds exist as tautomeric mixtures at the ground state and, in the case of Schiff bases, an excited-state intramolecular proton transfer (ESIPT) occurs upon excitation. The experimentally observed photophysical properties are discussed here in light of the theoretical findings. To rationalize the different experimentally observed radiative behavior of the azo and azomethine structures, a nonradiative decay pathway that is possibly active in such systems is determined. The characterization of this deactivation path, tested for two related compounds exhibiting different fluorescence quantum yields, enables us to disentangle the different and contrasting effects governing the excited-state behavior of these molecular systems.

Exploring the limits of recent exchange–correlation functionals in modeling lithium/benzene interaction

The interaction of the lithium alkaline metal, with the benzene molecule, is herein investigated in the framework of density functional theory (DFT) method. Performances of a large set of exchange–correlation functionals in reproducing some physical properties are benchmarked using as reference the CCSD(T) method at the complete basis set limit (CCSD(T)/CBS). Both the cationic and neutral lithium–benzene systems (LiBz+ and LiBz) are considered as well as the sandwich compound (BzLiBz+). Among all the functionals, ωB97X emerges as the best approach for modeling all the three systems analyzed, while large deviations are observed for several functionals in the case of the problematic neutral Li–benzene system. Particular attention was devoted to the discussion of the results obtained with methods containing empirical dispersion corrections. More broadly, our results underline the difficulties and the limits of current DFT approaches in the description of the interaction of Li with aromatic molecules, which is relevant in several applied fields.