Multifunctional Sensors for Successive Detection of Endogenous ONOO- and Mitochondrial Viscosity: Discriminating Normal to Cancer Models.

Diagnosing cancer in its early stages can play an important role in prolonging the lifespan of patients, which demands the use of powerful tools to detect biomarkers accurately. However, since most fluorescent probes described for cancer diagnosis are limited to recognizing a single molecule, achieving the high accuracy criteria remains difficult. Here, sensor 1 is constructed for the sequential detection of D, ONOO-, and viscosity. Initially, sensor 1 detected D and underwent an intramolecular charge transfer mechanism, resulting in the formation of 2 and fluorescence quenching at 587 nm. Subsequently, the intermediate (2) monitored ONOO- and reproduced sensor 1 reversibly with fluorescence enhancement at 496 nm, showing concentration-related quantitative analysis. Similar sensing processes were observed in monitoring ONOO- and viscosity by synthetically developed sensor 2. The proposed mechanisms of sensors 1 and 2 are verified through various characterizations (1H NMR, HR-MS, and HPLC) and DFT calculations. Investigations on endogenous ONOO- and mitochondrial viscosity in cancer (HeLa) and normal (NCM460) cells were conducted to distinguish cancerous cells from normal cells. We anticipated that sensor 2 could effectively serve as a reliable bioanalytical reagent for cancer diagnosis at an earlier stage through sequential detection of two cancer markers, ONOO- and mitochondrial viscosity, in living cells. Importantly, sensor 2 has been employed for imaging ONOO- in normal and liver injury mouse models and tissues, achieving outstanding results.

Why Does the Optimal Tuning Method of the Range Separation Parameter of a Long-Range Corrected Density Functional Fail in Intramolecular Charge Transfer Excitation Calculations?

We performed intra- and intermolecular charge transfer (CT) excitation energy calculations of (a) conjugated carbon chain [H2N-(CH=CH)n-X] and (b) its equidistant H2NH∙∙∙HX (n = 2~8) with various electron acceptors (X = NH2, OH, Cl, CHO, CN, and NO2) using EOM-CCSD, time-dependent (TD) Hartree-Fock (HF) and various density functional theory (DFT) functionals, such as BLYP, B3LYP, long-range corrected (LC) DFT, and LC-DFT with an optimally tuned (OT) range separation parameter (µ) using Koopman's theorem to investigate the effect of the electron-withdrawing (or -donating) strength of end-capped functional group (X) and CT distance (R) on intra- and intermolecular CT excitation energies. As the electron-withdrawing strength of X increases, both intra- and intermolecular CT excitation energies tend to decrease, since energy gaps between orbitals corresponding to CT excitations (e.g., HOMO and LUMO) decrease. However, the effect of the electron-withdrawing group on intramolecular CT excitation energy is negligible (at most 0.5 eV). OT-LC-DFT shows accurate intermolecular CT excitation energy, but worse results in intramolecular CT excitation energy than LC-DFT with the default µ value (0.47). Therefore, we conclude that the optimal tuning method is not effective in predicting intramolecular CT excitation energy. While intermolecular CT excitation energy has excitonic binding energy with asymptotic behavior to CT distance that is not affected by the choice of range separation parameter, intramolecular CT excitation energy is affected by orbital relaxation energy, which strongly depends on the choice of range separation parameter, which makes the OT method of range separation parameter ineffective in predicting intramolecular CT excitation energy as well as local excitation with high accuracy.

Computational Investigation of Conformational Properties of Short Azapeptides: Insights from DFT Study and NBO Analysis.

Azapeptides have gained much attention due to their ability to enhance the stability and bioavailability of peptide drugs. Their structural preferences, essential to understanding their function and potential application in the peptide drug design, remain largely unknown. In this work, we systematically investigated the conformational preferences of three azaamino acid residues in tripeptide models, Ac-azaXaa-Pro-NHMe [Xaa = Asn (4), Asp (5), Ala (6)], using the popular DFT functionals, B3LYP and B3LYP-D3. A solvation model density (SMD) was used to mimic the solvation effect on the conformational behaviors of azapeptides in water. During the calculation, we considered the impact of the amide bond in the azapeptide models on the conformational preferences of models 4-6. We analyzed the effect of the HB between the side-chain main chain and main-chain main-chain on the conformational behaviors of azapeptides 4-6. We found that the predicted lowest energy conformation for the three models differs depending on the calculation methods. In the gas phase, B3LYP functional indicates that the conformers tttANP-1 and tttADP-1 of azapeptides 4 and 5 correspond to the type I of ß-turn, the lowest energy conformation with all-trans amide bonds. Considering the dispersion correction, B3LYP-D3 functional predicts the conformers tctANP-2 and tctADP-3 of azapeptide 4 and 5, which contain the cis amide bond preceding the Pro residue, as the lowest energy conformation in the gas phase. The results imply that azaAsx and Pro residues may involve cis-trans isomerization in the gas phase. In water, the predicted lowest energy conformer of azapeptides 4 and 5 differs from the gas phase results and depends on the calculational method. For azapeptide 6, regardless of calculation methods and phases, tttAAP-1 (ß-I turn) is predicted as the lowest energy conformer. The results imply that the effect of the side chain that can form HBs on the conformational preferences of azapeptides 4 and 5 may not be negligible. We compared the theoretical results of azaXaa-Pro models with those of Pro-azaXaa models, showing that incorporating azaamino acid residue in peptides at different positions can significantly impact the folding patterns and stability of azapeptides.

Assessment of long-range corrected density functional theory on the absorption and vibrationally resolved fluorescence spectrum of carbon nanobelts.

Time-dependent (TD) density functional theory (DFT) and Franck-Condon Hertzberg-Teller (FCHT) calculations of various DFT functionals [B3LYP, CAM-B3LYP, ωB97XD, and optimally tuned (OT) long-range corrected (LC)-BLYP] were performed to examine how well DFT functionals can predict the experimental absorption and fluorescence spectra of a 12-carbon nanobelt (CNB). OT-LC-BLYP reproduced the experimental absorption spectrum well in terms of the peak position and intensity in the case of using a basis set with a diffuse function, such as 6-31+G(d,p) and 6-311+G(d,p), whereas B3LYP showed a red-shift in the peak positions and CAM-B3LYP and ωB97XD, which have a long-range HF exchange, showed blue shifts. Regarding the fluorescence spectrum calculations with FCHT using 6-311+G(d,p), the OT-LC-BLYP reproduced both the peak intensities and positions closest to the experimental spectrum. B3LYP, however, showed red-shifted peaks, and ωB97XD showed blue-shifted peaks. CAM-B3LYP provided less blue-shifted peaks, but the relative peak intensities mismatched the experimental ones. Furthermore, calculations of the absorption and vibrationally resolved fluorescence spectra of 16-CNB and 24-CNB using OT-LC-BLYP/6-311+G(d,p) showed absorption and fluorescence spectra close to the experimental spectra with high accuracy. Moreover, the application of a polarizable continuum model (dichloromethane) produced a red shift in the peak positions of the absorption spectrum with increasing intensity but an increase in the peak intensities of the fluorescence calculations without shifting the peak position.

Koopmans'-Type Theorem in Kohn-Sham Theory with Optimally Tuned Long-Range-Corrected (LC) Functionals.

In the present study, we have investigated the applicability of long-range-corrected (LC) functionals to a Kohn-Sham (KS) Koopmans'-type theorem. Specifically, we have examined the performance of optimally tuned LCgau-core functionals (in combination with BOP and PW86-PW91 exchange-correlation functionals) by calculating the ionization potential (IP) within the context of Koopmans' prediction. In the LC scheme, the electron repulsion operator, 1/r12, is divided into short-range and long-range components using a standard error function, with a range separation parameter µ determining the weight of the two ranges. For each system that we have examined (H2O, CO, benzene, N2, HF, H2CO, C2H4, and five-membered ring compounds cyclo-C4H4X, with X = CH2, NH, O, and S, and pyridine), the value of µ is optimized to minimize the deviation of the negative HOMO energy from the experimental IP. Our results demonstrate the utility of optimally tuned LC functionals in predicting the IP of outer valence levels. The accuracy is comparable to that of highly accurate ab initio theory. However, our Koopmans' method is less accurate for the inner valence and core levels. Overall, our results support the notion that orbitals in KS-DFT, when obtained with the LC functional, provide an accurate one-electron energy spectrum. This method represents a one-electron orbital theory that is attractive in its simple formulation and effective in its practical application.

Predicting whether aromatic molecules would prefer to enter a carbon nanotube: A density functional theory study.

The interaction of a carbon nanotube (CNT) with various aromatic molecules, such as aniline, benzophenone, and diphenylamine, was studied using density functional theory able to compute intermolecular weak interactions (B3LYP-D3). CNTs of varying lengths were used, such as 4-CNT, 6-CNT, and 8-CNT (the numbers denoting relative lengths), with the lengths being chosen appropriately to save computation times. All aromatic molecules were found to exhibit strong intermolecular binding energies with the inner surface of the CNT, rather than the outer surface. Hydrogen bonding between two aromatic molecules that include N and O atoms is shown to further stabilize the intermolecular adsorption process. Therefore, when benzophenone and diphenylamine were simultaneously allowed to interact with a CNT, the aromatic molecules were expected to preferably enter the CNT. Furthermore, additional calculations of the intermolecular adsorption energy for aniline adsorbed on a graphene surface showed that the concavity of graphene-like carbon sheet is in proportion to the intermolecular binding energy between the graphene-like carbon sheet and the aromatic molecule.

Excitation energies expressed as orbital energies of Kohn-Sham density functional theory with long-range corrected functionals.

A new simple and conceptual theoretical scheme is proposed for estimating one-electron excitation energies using Kohn-Sham (KS) solutions. One-electron transitions that are dominated by the promotion from one initially occupied orbital to one unoccupied orbital of a molecular system can be expressed in a two-step process, ionization, and electron attachment. KS with long-range corrected (LC) functionals satisfies Janak's theorem and LC total energy varies almost linearly as a function of its fractional occupation number between the integer electron points. Thus, LC reproduces ionization energies (IPs) and electron affinities (EAs) with high accuracy and one-electron excitation energies are expressed as the difference between the occupied orbital energy of a neutral molecule and the corresponding unoccupied orbital energy of its cation. Two such expressions can be used, with one employing the orbital energies for the neutral and cationic systems, while the other utilizes orbital energies of just the cation. Because the EA of a molecule is the IP of its anion, if we utilize this identity, the two expressions coincide and give the same excitation energies. Reasonable results are obtained for valence and core excitations using only orbital energies.

Core-Level Excitation Energies of Nucleic Acid Bases Expressed as Orbital Energies of the Kohn-Sham Density Functional Theory with Long-Range Corrected Functionals.

The core electron binding energies (CEBEs) and core-level excitation energies of thymine, adenine, cytosine, and uracil are studied by the Kohn-Sham (KS) method with long-range corrected (LC) functionals. The CEBEs are estimated according to the Koopmans-type theorem for density functional theory. The excitation energies from the core to the valence π* and Rydberg states are calculated as the orbital energy differences between core-level orbitals of a neutral parent/cation and unoccupied π* or Rydberg orbitals of its cation. The model is intuitive, and the spectra can easily be assigned. Core excitation energies from oxygen 1s, nitrogen 1s, and carbon 1s to π* and Rydberg states, and the chemical shifts, agree well with previously reported theoretical and experimental data. The straightforward use of KS orbitals in this scheme carries the advantage that it can be applied efficiently to large systems such as biomolecules and nanomaterials.

Charge-Transfer Excitation Energies Expressed as Orbital Energies of Kohn-Sham Density Functional Theory with Long-Range Corrected Functionals.

Previously proposed theoretical schemes for estimating one-electron excitation energies using Kohn-Sham (KS) solutions with long-range corrected (LC) functionals are applied to the charge-transfer (CT) excitations of the ethylene···tetrafluoroethylene (C2H4-C2F4) system, and the CT complex between an aromatic donor (Ar = benzene, toluene, o-xylene, naphthalene, anthracene, and various meso-substituted anthracenes) and the tetracyanoethylene (TCNE) acceptor. The CT excited state is described well as a single-electron excitation between specific orbitals of donor and acceptor. Thus, CT excitation energies are well approximated by the orbital energies because of the satisfaction of the Koopmans-type theorem and the asymptotic behavior of the LC functional. We have examined three computational schemes: scheme 1 employs the orbital energies for the neutral and cationic systems, scheme 2 utilizes orbital energies of just the cation, and in scheme 3, because the electron affinity of a molecule is the ionization energy of its anion, a scale factor is applied to enforce this identity. The present schemes reproduce the correct asymptotic behavior of CT excitation energy of C2H4···C2F4 for the long intermolecular distances and give good agreement with accurate ab initio results. Calculated CT excitation energies for Ar-TCNE are compared with those of TD-DFT and ΔSCF methods. Scheme 1 with the optimal range-separation parameter µ accurately reproduces CT excitation energies for all Ar-TCNE systems and gives good agreement with the best TD-DFT calculations and experiment. Scheme 1, scheme 3, and TD-DFT show similar tendencies with respect to the variation in µ. Scheme 2 and ΔSCF approaches are rather insensitive to changes in µ, but both considerably underestimate the CT excitation energies for these systems. KS orbital energies are physically meaningful and they are practically useful; if the range-separation parameter is tuned, then good results can be obtained.

Application of accelerated long-range corrected exchange functional [LC-DFT(2Gau)] to periodic boundary condition systems: CO adsorption on Cu(111) surface.

Several different types of density functional theory (DFT) exchange correlation functionals were applied to a periodic boundary condition (PBC) system [carbon monoxide (CO) adsorbed on Cu(111): CO/Cu(111)] and the differences in the results calculated using these functionals were compared. The exchange correlation functionals compared were those of Perdew-Burke-Ernzerhof (PBE) and those of long-range corrected density functional theory (LC-DFT), such as LC-ωPBE(2Gau) and LC-BLYP(2Gau). Solid state properties such as the partial density of states were calculated in order to elucidate the detailed adsorption mechanisms and back-bonding peculiar to the CO/Cu(111) system. In addition, our benchmark analysis of the correlations among the orbitals of CO and Cu metal using LC-DFT reasonably was in line with the experimentally observed adsorption site. The computation time was reasonable, and other numerical results were found to agree well with the experimental results and also with the theoretical results of other researchers. This suggests that the long-range Hartree-Fock exchange integral should be included to correctly predict the electronic nature of PBC systems.

Accelerated long-range corrected exchange functional using a two-gaussian operator combined with one-parameter progressive correlation functional [LC-BOP(2Gau)].

Recently, we proposed a simple yet efficient method for the computation of a long-range corrected (LC) hybrid scheme [LC-DFT(2Gau)], which uses a modified two-Gaussian attenuating operator instead of the error function for the long-range HF exchange integral. This method dramatically reduced the computational time while maintaining the improved features of the LC density functional theory (DFT). Here, we combined an LC hybrid scheme using a two-Gaussian attenuating operator with one-parameter progressive correlation functional and Becke88 exchange functional with varying range-separation parameter values [LC-BOP(2Gau) with various µ values of 0.16, 0.2, 0.25, 0.3, 0.35, 0.4, and 0.42] and demonstrated that LC-BOP(2Gau) reproduces well the thermochemical and frontier orbital energies of LC-BOP. Additionally, we revised the scaling factors of the Gaussian multipole screening scheme for LC-DFT(2Gau) to correspond to the angular momentum of orbitals, which decreased the energy deviations from the energy with the no-screening scheme. © 2018 Wiley Periodicals, Inc.

Importance of van der Waals Descriptions on Accurate Isomerization Energy Calculations of Thiourea Compounds: LCgau-BOP+LRD Method.

We have previously reported that, whereas conventional density functional theory (DFT) functionals have provided poor calculations on the alkane isodesmic reaction energy and isomerization reaction energy of organic molecules that include C, N, and O atoms, our developed long-range corrected (LC)- and LC including Gaussian attenuation (LCgau)-DFT + local response dispersion (LRD) functionals, which can accurately calculate inter- and intramolecular weak interactions, give accurate isomerization energies on these reactions. In this work, we found that B3LYP-D3, LC-ωPBE-D3, and ωB97XD, known for their good descriptions of weak interaction calculations, fail to reproduce the isomerization reaction energies of the molecules that include the S atom, such as methyl-thiourea, ethyl-thiourea, and propyl-thiourea. In contrast, LC- and LCgau-BOP+LRD functionals provide isomerization reaction energies that are very close to those produced by highly accurate wave function methods. These results show that an accurate description of the intramolecular weak interaction between the alkyl group and the S atom, unlike in the case of urea, is significant to reproduce the correct energy of the molecules with an alkyl group and S atom.

A Density Functional Theory-Based Scheme to Compute the Redox Potential of a Transition Metal Complex: Applications to Heme Compound.

We estimated the redox potential of a model heme compound by using the combination of our density functionals with a computational scheme, which corrects the solvation energy to the normal solvent model. Among many density functionals, the LC-BOP12 functional gave the smallest mean absolute error of 0.16 V in the test molecular sets. The application of these methods revealed that the redox potential of a model heme can be controlled within 200 mV by changing the protonation state and even within 20 mV by the flipping of the ligand histidine. In addition, the redox potential depends on the inverse of the dielectric constant, which controls the surroundings. The computational results also imply that a system with a low dielectric constant avoids the charged molecule by controlling either the redox potential or the protonation system.

Facile Supramolecular Processing of Carbon Nanotubes and Polymers for Electromechanical Sensors.

We herein report a facile, cost-competitive, and scalable method for producing viscoelastic conductors via one-pot melt-blending using polymers and supramolecular gels composed of carbon nanotubes (CNTs), diphenylamine (DP), and benzophenone (BP). When mixed, a non-volatile eutectic liquid (EL) produced by simply blending DP with BP (1:1 molar ratio) enabled not only the gelation of CNTs (EL-CNTs) but also the dissolution of a number of commodity polymers. To make use of these advantages, viscoelastic conductors were produced via one-pot melt-blending the EL and CNTs with a model thermoplastic elastomer, poly(styrene-b-butadiene-b-styrene) (SBS, styrene 30 wt %). The resulting composites displayed an excellent electromechanical sensory along with re-mendable properties. This simple method using cost-competitive EL components is expected to provide an alternative to the use of expensive ionic liquids as well as to facilitate the fabrication of novel composites for various purposes.

Performance of the OP correlation functional in relation to its formulation: Influence of the exchange component and the effect of incorporating same-spin correlations.

In the present study, we have investigated two significant features of the OP correlation functional, namely the incorporation of the exchange functional into itself, and the inclusion of only opposite-spin (OS) effects. To explore the latter feature, we have compared OP with B95 and a new functional introduced in the present study - the OPB method that combines OP with the same-spin (SS) component of B95. In general, we find that B95 and OPB perform comparably. Our comparisons of the various DFT procedures suggest that the incorporation of a meta-GGA (e.g., TPSS) into OP and OPB does not necessarily lead to a chemically more accurate procedure than the use of a related GGA (e.g., PBE). An important finding is the more notable (and somewhat more consistent) improvement in performance with the incorporation of SS correlation, particularly for longer-range chemical properties. Nonetheless, on average across our test sets of over 800 systems, the difference between the performances of OP versus B95 or OPB is not exceedingly large. By drawing a parallel between these DFT methods and the wavefunction scaled-MP2-type methods, we reason that one can further develop the OP functional, and perhaps a wider range of correlation functionals by combining it with the technique of range separation.

Blind test of density-functional-based methods on intermolecular interaction energies.

In the past decade, a number of approaches have been developed to fix the failure of (semi)local density-functional theory (DFT) in describing intermolecular interactions. The performance of several such approaches with respect to highly accurate benchmarks is compared here on a set of separation-dependent interaction energies for ten dimers. Since the benchmarks were unknown before the DFT-based results were collected, this comparison constitutes a blind test of these methods.

Toward the complete range separation of non-hybrid exchange-correlation functional.

In this study, we use a very simple scheme to achieve range separation of a total exchange-correlation functional. We have utilized this methodology to combine a short-range pure density functional theory (DFT) functional with a corresponding long-range pure DFT, leading to a "Range-separated eXchange-Correlation" (RXC) scheme. By examining the performance of a range of standard exchange-correlation functionals for prototypical short- and long-range properties, we have chosen B-LYP as the short-range functional and PBE-B95 as the long-range counterpart. The results of our testing using a more diverse range of data sets show that, for properties that we deem to be short-range in nature, the performance of this prescribed RXC-DFT protocol does resemble that of B-LYP in most cases, and vice versa. Thus, this RXC-DFT protocol already provides meaningful numerical results. Furthermore, we envisage that the general RXC scheme can be easily implemented in computational chemistry software packages. This study paves a way for further refinement of such a range-separation technique for the development of better performing DFT procedures.

Efficient method of evaluation for Gaussian Hartree-Fock exchange operator for Gau-PBE functional.

We previously developed an efficient screened hybrid functional called Gaussian-Perdew-Burke-Ernzerhof (Gau-PBE) [Song et al., J. Chem. Phys. 135, 071103 (2011)] for large molecules and extended systems, which is characterized by the usage of a Gaussian function as a modified Coulomb potential for the Hartree-Fock (HF) exchange. We found that the adoption of a Gaussian HF exchange operator considerably decreases the calculation time cost of periodic systems while improving the reproducibility of the bandgaps of semiconductors. We present a distance-based screening scheme here that is tailored for the Gaussian HF exchange integral that utilizes multipole expansion for the Gaussian two-electron integrals. We found a new multipole screening scheme helps to save the time cost for the HF exchange integration by efficiently decreasing the number of integrals of, specifically, the near field region without incurring substantial changes in total energy. In our assessment on the periodic systems of seven semiconductors, the Gau-PBE hybrid functional with a new screening scheme has 1.56 times the time cost of a pure functional while the previous Gau-PBE was 1.84 times and HSE06 was 3.34 times.

Long-range corrected density functional theory with accelerated Hartree-Fock exchange integration using a two-Gaussian operator [LC-ωPBE(2Gau)].

Since the advent of hybrid functional in 1993, it has become a main quantum chemical tool for the calculation of energies and properties of molecular systems. Following the introduction of long-range corrected hybrid scheme for density functional theory a decade later, the applicability of the hybrid functional has been further amplified due to the resulting increased performance on orbital energy, excitation energy, non-linear optical property, barrier height, and so on. Nevertheless, the high cost associated with the evaluation of Hartree-Fock (HF) exchange integrals remains a bottleneck for the broader and more active applications of hybrid functionals to large molecular and periodic systems. Here, we propose a very simple yet efficient method for the computation of long-range corrected hybrid scheme. It uses a modified two-Gaussian attenuating operator instead of the error function for the long-range HF exchange integral. As a result, the two-Gaussian HF operator, which mimics the shape of the error function operator, reduces computational time dramatically (e.g., about 14 times acceleration in C diamond calculation using periodic boundary condition) and enables lower scaling with system size, while maintaining the improved features of the long-range corrected density functional theory.

Long-range Corrected Density Functional Theory Including a Two-Gaussian Hartree-Fock Operator for High Accuracy Core-excitation Energy Calculations of Both the Second- and Third-Row Atoms (LC2gau-core-BOP).

In the previous work, LCgau-core-BOP, which includes the short-range interelectronic Gaussian attenuating Hartree-Fock (HF) exchange to the long-range HF exchange, showed high accuracy core-excitation energies from 1s orbitals of the second-row atoms (1s → π*, 1s → σ*, 1s → n*, and 1s → Rydberg), but underestimates the core-excitation energies from 1s orbitals of the third-row atoms. To improve this, we added one more Gaussian attenuating HF exchange to LCgau-core-BOP. We named it LC2gau-core-BOP, which achieves a mean absolute error (MAE) of 0.6 and 0.3 eV for core excitation energies of the second- and third-row atoms of the tested small molecules, respectively. We found that the inclusion of the short-range interelectronic HF exchange at a distance ranging from 0.2 to 0.6 a.u. contributes to the increase of performances on 1s orbital energy calculations of the second-row atoms, while the inclusion of more short-range interelectronic HF exchange at a distance ranging from 0 to 0.2 a.u. does to the increase of performance on 1s orbital energy calculations of the third-row atoms. It is notable that all of these improvements were accomplished using flexible Gaussian attenuating HF exchange inclusion. LC2gau-core-BOP shows deviations of less than 0.8 eV from experimental values for all of the core-excitation energies of the tested medium-size molecules consisting of thymine, oxazole, glycine, and dibenzothiophene sulfone. Moreover, by optimizing one parameter of the OP correlation functional, LC2gau-core-BOP provides atomization energies over the G3 test set with an accuracy comparable to that of B3LYP.