NMR screening method based on 19F spin-spin relaxation time for analyses of fluorinated compound bound to proteins.

NMR screening methods based on 19F spin-spin relaxation time (19F-T2) were applied to fluorinated compounds bound to human serum albumin. Diflunisal and fleroxacin (the fluorinated compounds) contain two and three fluorine atoms per molecule, respectively, and are suitable as the model system for 19F NMR analysis. It was shown that 19F-T2 was more sensitive in monitoring the binding affinity to the target protein than 19F spin-lattice relaxation time (19F-T1). The comparisons of 19F signal intensities acquired at different echo times using 19F-T2 pulse sequence were also shown to be an effective means of assessing complex formation for fluorinated compounds.

Effects of environmental factors on the fleroxacin photodegradation with the identification of reaction pathways.

The abuse of fluoroquinolones (FQs) antibiotics leads to bacterial resistance and environmental pollution, so it is of great significance to verify the decomposition mechanism for eliminating antibiotic efficiently and conveniently. The effects of various environmental factors and the fleroxacin (FLE) photodegradation mechanisms were investigated by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS), UV-Vis absorption spectroscopy, fluorescence spectroscopy and quantum chemical calculation. Six possible photodegradation reaction paths on T1 (excited triplet state) were proposed and simulated. The departure of the piperazine ring and the substitution of F atom at C-6 position by OH group were determined as the main reactions based on the reaction rates and energy barriers of each path. The multi-pathway reactions resulted in the fastest photodegradation rates of FLE at pH 6-7 than other pH conditions. NaN3 would promote FLE photodegradation by inhibiting the reverse reaction of the separation process of F atom at C-8 and the generation of biphenyl molecules, which was a novel and distinctive phenomenon in this report. ·OH would rapidly combine with the free radicals generated in photolysis processes and made a great contribution to FLE photodegradation. Ca2+, Mg2+ and Ba2+ could stabilize the carboxyl group to impede the photo-competitive process of the decarboxylation reaction, while NO3- could generate reactive oxygen species to promote photodegradation.

Association between fluoroquinolone exposure and children's growth and development: A multisite biomonitoring-based study in northern China.

BACKGROUND: Although animal experiments found that antibiotic exposure during early life increased adiposity, limited human epidemiological evidence is available for the effects of veterinary antibiotic exposure on children's growth and development. OBJECTIVE: This study was conducted to examine the body burden of fluoroquinolones in northern Chinese children and assess its association with growth and development. METHODS: After recruiting 233 children aged 0-15 years from 12 different sites in northern China in 2020, we measured urinary concentrations of 5 respective fluoroquinolones (fleroxacin, ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin) by high performance liquid chromatography. Categories of children's growth and development were identified based on the Z score of body mass index. The health risks of individual and combined antibiotic exposure were estimated by the hazard quotient (HQ) and hazard index (HI), respectively. The association between children's growth and development with antibiotic concentrations was evaluated via multiple logistic regression analysis. RESULTS: In total, 4 antibiotics, fleroxacin, ofloxacin, ciprofloxacin, and enrofloxacin, were found in urine samples of northern Chinese children at an overall frequency of 57.08%. Due to diet and economic differences, antibiotic concentrations in urine samples differed by study area, and the highest concentrations were found in Tianjin, Henan, and Beijing. The percentage of the participants with HQ > 1 caused by ciprofloxacin exposure was 20.61%, and the HI values in 23.18% of samples exceeded 1, suggesting potential health risks. The odds ratio (95% confidence interval) of overweight or obesity risk of tertile 2 of enrofloxacin was 3.01 (1.12, 8.11), indicating an increase in overweight or obesity risk for children with middle-concentration enrofloxacin exposure. CONCLUSION: This is the first study to show a positive association of enrofloxacin internal exposure with overweight or obesity risk in children, demonstrating that more attention should be given to the usage and disposal of fluoroquinolones to safeguard children's health.

Development of 1H{19F} saturation transfer difference experiments for detection of a fluorinated compound bound to proteins.

The 1H{19F} saturation transfer difference (STD) experiment presented here incorporates the WATERGATE W5 sequence to observe protein-ligand interactions in a human serum albumin (HSA)-fleroxacin complex. In conventional STD experiments, 1H of proteins are first saturated, and the ligands bound to these proteins are then observed. The method proposed here reverses this process: fluorine atoms in fleroxacin are selectively saturated, and saturation transfer then occurs to protons of fleroxacin as well as to those of HSA. The combined use of the present 1H{19F} STD and conventional STD methods is expected to provide better insight in the analysis of the role of fluorine atoms in a fluorinated compound.

Comparison of fleroxacin oxidation by chlorine and chlorine dioxide: Kinetics, mechanism and halogenated DBPs formation.

Fleroxacin (FLE) is a widely used fluoroquinolones to cure urinary tract infections and respiratory disease, which has been frequently detected in the aquatic environment. The reactivity kinetics of FLE by chlorine and chlorine dioxide (ClO2) and transformation mechanism were investigated in this study. The results showed that FLE was degraded efficiently by chlorine and ClO2, and both reactions followed second-order kinetics overall. The increase of disinfectant dosage and temperature would enhance the degradation of FLE. The highest removal of FLE by chlorine was achieved at a neutral condition (pH 7.4), whereas ClO2 reaction rates increased dramatically with the increasing pH in this study condition. The number of intermediates identified in FLE chlorination and ClO2 oxidation was seven and ten, respectively. The piperazine ring cleavage was the principal and initial reaction in both above reactions. Then, the removal of the piperazine group was predominantly in FLE removal by chlorine, while the decarboxylation mainly occurred in FLE removal by ClO2. The intermediates increased first and then decreased with time, while three kinds of halogenated DBPs increased with time, indicating the above-identified intermediates were further transformed to the halogenated DBPs. Additionally, compared to chlorine reaction, the reaction of ClO2 with FLE reduced the formation of halogenated DBPs, but it also induced the formation of chlorite. The analysis of toxicity showed that compared with chlorination, the oxidation of ClO2 was more suitable for FLE removal.

Establishment of an immunological detection method of fleroxacin by fluorescence-linked immunosorbent assay.

The direct and indirect competitive fluorescence-linked immunosorbent assay (FLISA and icFLISA) incorporating quantum dots (QDs) for the detection of fleroxacin (FLE) was established for the first time in this study. The monoclonal antibody specific for FLE was successfully conjugated with QDs after purification by the caprylic acid-ammonium sulphate method. The limits of detection of FLISA and icFLISA were 0.012 ng/mL and 0.006 ng/mL, respectively; IC50 were 0.32 ng/mL and 0.19 ng/mL; and the detection ranges were 0.012-24.490 ng/mL and 0.006-16.210 ng/mL. The recovery was 93.8%-112.4% and the coefficient of variation was below 11.75%. The fabricated FLISA and icFLISA are cost-effective, high sensitive and can be an alternative method in the detection of FLE residues.

Collection and Separation of Fleroxacin and Ciprofloxacin in Ultrasound-Assisted Ionic Liquid Salting-Out Microextraction System.

An ultrasound-assisted ionic liquid (IL) salting-out microextraction system was developed and applied for the extraction of quinolone antibiotics from urine. A precipitate was formed from the salt and IL, and it acted as the sorbent for the analytes. The precipitate containing the analyte was separated by filtration, redissolved, and the solution then was evaporated. The resulting extract was redissolved for high-performance liquid chromatographic analysis. Several parameters, including type and volume of IL, the type and amount of salts, sample pH, temperature and extraction time were optimized. Under the optimal experimental conditions, the limits of detection for fleroxacin and ciprofloxacin were 3.12 and 4.97 µg L-1, respectively. When the present method was applied to real urine sample analysis, the analyte recoveries ranged from 82.3 to 106.8%. This ultrasound-assisted IL salting-out microextraction system had the characteristics of high recoveries, shorter separation time and easy-to-perform collection procedure, which yielded the method to have potential for wide application.

Identification of Binding Epitopes of a Fluorinated Compound Bound to Proteins Using 1H and 19F NMR Spectroscopy.

1H/19F NMR-based screening methods were applied to a human serum albumin-fleroxacin complex. Fleroxacin contains three fluorine atoms in a molecule, which is suitable as a model fluorinated compound for NMR analysis with 1H and 19F detection. The 19F{1H} and 1H{1H} saturation transfer difference spectra were acquired and the 1H/19F spin-lattice relaxation rates were measured with and without any selective irradiation of protein resonance to identify the binding epitopes of fleroxacin. Because several 1H signals of fleroxacin resonated close to water, its precise signal intensities were unavailable. The 19F NMR-based screening methods successfully provide complementary information, indicating its importance in the analysis of fluorinated compounds.

A highly sensitive and selective "turn-on" fluorescent probe for detection of fleroxacin in human serum and urine based on a lanthanide functionalized metal-organic framework.

Cation exchange, a facile and non-destructive post-synthetic modification method, is applied to [(Me)4N]2[Pb6K6(m-BDC)9(OH)2]·H2O (1) (1,3-H2BDC = 1,3-benzenedicarboxylic acid) to prepare a series of lanthanide functionalized metal-organic frameworks. The fluorescence properties of Ln3+@1 (Ln = Eu, Tb, Sm and Dy) are investigated. The results demonstrate that the framework of 1 is capable of sensitizing both Eu3+ and Tb3+ ions effectively. Remarkably, the rapid and stable fluorescence sensitization of Eu3+@1 can be observed in the presence of fleroxacin in aqueous solution, indicating that the hybrid system can be designed as a highly sensitive and selective probe for fleroxacin. As a novel "turn-on" fluorescent probe, Eu3+@1 is regarded as a promising candidate for applications in clinical diagnosis, due to its merits of high antidisturbance, chemical stability and a low detection limit (43.91 ng mL-1). In this paper, the practical application of luminescent Eu3+@1 is highlighted, and its possible sensing mechanism is also described.

Investigation of binding between fluoroquinolones and pepsin by fluorescence spectroscopy and molecular simulation.

In this paper, the interactions of pepsin with fluoroquinolones, including norfloxacin (NFX) or ofloxacin (OFX), were investigated using fluorescence spectroscopy. The effects of NFX or OFX on pepsin showed that the molecular conformation of pepsin and the microenvironment of tryptophan residues were changed under mimicked physiological conditions. Static quenching was suggested as a factor. Quenching constants and binding constants were determined and thermodynamic parameters were calculated at three temperatures (25°C, 31°C and 37°C). Molecular interaction distances (binding distance r) were obtained. Binding was enthalpy driven and the process was spontaneous. Synchronous fluorescence, three-dimensional fluorescence spectroscopy and molecular simulation were used for analysis. Interactions were further tested using molecular modelling. Quenching and binding constants of NFX with pepsin were the highest when testing NFX/OFX/fleroxacin/gatifloxacin with pepsin combinations. NFX was the strongest quencher, and affinity of NFX for pepsin was higher than that of OFX/fleroxacin/gatifloxacin.

Antibiotics and efflux: combined spectrofluorimetry and mass spectrometry to evaluate the involvement of concentration and efflux activity in antibiotic intracellular accumulation.

Background: In Gram-negative bacteria, passing through the double membrane barrier to reach the inhibitory concentration inside the bacterium is a pivotal step for antibiotic activity. Spectrofluorimetry has been developed to follow fluoroquinolone accumulation inside bacteria using intrinsic bacterial fluorescence as an internal standard. However, adaptation for non-fluorescent antibiotics is needed; quantitative methods based on MS offer the possibility of expanding the detection range obtained by spectrofluorimetry. Objectives: To validate, with spectrofluorimetry, the use of MS to measure antibiotic accumulation in cells and to determine the relationship between antibiotic concentrations and the amount of intrabacterial accumulation in different efflux backgrounds on the same batch of molecules. Methods: Spectrofluorimetry was performed in parallel with MS on the same samples to measure the ciprofloxacin and fleroxacin accumulation in cells expressing various efflux pump levels. A microplate protocol was set up to determine the antibiotic accumulation as a function of external antibiotic concentrations. Results: A correlation existed between the data obtained with spectrofluorimetry and MS, whatever the efflux pump or tested antibiotic. The results highlighted different dynamics of uptake between ciprofloxacin and fleroxacin as well as the relationship between the level of efflux activity and antibiotic accumulation. Conclusions: We have developed a microplate protocol and cross-validated two complementary methods: spectrofluorimetry, which contains a reliable internal standard; and MS, which allows detection of low antibiotic amounts. These assays allow study of the dose effect and the efflux impact on the intrabacterial accumulation of antibiotics.

First population pharmacokinetic analysis showing increased quinolone metabolite formation and clearance in patients with cystic fibrosis compared to healthy volunteers.

Understanding the pharmacokinetics in patients with cystic fibrosis (CF) is important for dosing. For antibiotics with extensive metabolism, however, a comparison of metabolite formation and elimination between patients with CF and healthy volunteers has never been performed via population modeling. We aimed to compare the population pharmacokinetics of fleroxacin and its N­oxide and demethyl metabolites between patients with CF and healthy volunteers. Our analysis included eleven adult patients with CF and twelve healthy volunteers who received 800 mg fleroxacin as a single oral dose followed by five doses every 24 h from a previously published study. All plasma concentrations and amounts in urine for fleroxacin and its metabolites were simultaneously modelled. The estimates below accounted for differences in body size and body composition via allometric scaling by lean body mass. Oral absorption was slower in patients with CF than in healthy volunteers. For fleroxacin, the population mean in patients with CF divided by that in healthy volunteers was 1.12 for renal clearance, 1.01 for linear nonrenal clearance, 0.83 for saturable exsorption clearance into intestine, and 0.81 for volume of distribution. The formation clearances of N­oxide fleroxacin and N­demethylfleroxacin were 0.520 L/h and 0.496 L/h in patients with CF; these formation clearances were 0.378 L/h and 0.353 L/h in healthy volunteers. Renal clearance in patients with CF divided by that in healthy volunteers was 1.53 for N­oxide fleroxacin and 1.70 for N­demethyl fleroxacin. Allometric scaling by lean body mass best explained the variability. While fleroxacin pharmacokinetics was comparable, both formation and elimination clearances of its two metabolites were substantially larger in patients with CF compared to those in healthy volunteers.

Upconversion particle@Fe3O4@molecularly imprinted polymer with controllable shell thickness as high-performance fluorescent probe for sensing quinolones.

Localized photo-polymerization was ingeniously applied to prepare a multifunctional molecularly imprinted polymer (MIP) fluorescent probe using the "layer-by-layer" assembly of MIP and Fe3O4 nanoparticles on NaYF4: Yb3+, Er3+ upconversion particles (MUCPs@MIP). Enrofloxacin was used as the template and chosen as the target molecular during the investigation of the adsorption property. This ternary probe has magnetic and broad-spectrum molecular recognition capability, fast response, and upconversion fluorescence. The results of the fluorescence quenching analysis showed good linear ranges of 1.03nmol/L to 0.28µmol/L for enrofloxacin, 1.69nmol/L to 0.22µmol/L for fleroxacin, 6.92nmol/L to 0.28µmol/L for levofloxacin, 7.54nmol/L to 0.30µmol/L for ciprofloxacin, and 3.90nmol/L to 0.25µmol/L for enoxacin. This probe was further used to determine five quinolones in fish tissues and the recoveries ranging from 90.33% to 108.43% were obtained with relative standard deviation below 5.53%. This work offers a new and general strategy to synthesize a MUCPs@MIP upconversion fluorescence probe with magnetic and selective molecular recognition capability for rapid and accurate sensing of multiple chemical residues in the environment and agri-food products.

An automated magnetic dispersive micro-solid phase extraction in a fluidized reactor for the determination of fluoroquinolones in baby food samples.

An automated magnetic dispersive micro-solid phase extraction procedure in a fluidized reactor was developed for the determination of fluoroquinolone antimicrobial drugs (fleroxacin, norfloxacin and ofloxacin) in meat-based baby food samples. A stepwise injection system was successfully combined with afluidized reactorand applied for the magnetic dispersive micro-solid phase extraction procedure automation. The developed automated procedure involved injection of the sample solution into the fluidized reactor followed by the on-line separation of the analytes from the sample matrix based on fluidized beds strategy using magnetic nanoparticles, elution and determination of the analytes using a high performance liquid chromatography system with fluorescence detection. The floating of the magnetic nanoparticles in a liquid sample phase was accomplished by air-bubbling. In the developed method Zr-Fe-C magnetic nanoparticles were used as an efficient sorbent for the determination of fleroxacin, norfloxacin and ofloxacin. Under the optimal conditions, the calibration graphs were linear over the concentration ranges of 10-1000 µg L-1 for fleroxacin (R2 = 0.996), 5-1000 µg L-1for norfloxacin (R2 = 0.998) and ofloxacin (R2 = 0.998). The limits of detection, calculated from the blank tests based on 3σ, were 3.0 µg L-1forfleroxacin, 1.5 µg L-1for norfloxacin and ofloxacin. The limits of quantification, calculated from the blank tests based on 10σ, were 10 µg L-1 forfleroxacin, 5 µg L-1for norfloxacin and ofloxacin. The method was applied for the determination of fluoroquinolonesin meat-based baby food samples and the results were compared with those obtained by the reference method. The recovery values for all analytes were within of 86-122% range.

Development of photoprotective, antiphototoxic, and antiphotogenotoxic formulations of ocular drugs with fluoroquinolones.

The development of innovative solutions in photosafety of photolabile pharmaceutical products may help to reduce the adverse effects of these products, caused by light exposure. Providing new data in this area of study is particularly important in case of drugs applied topically on sensitive organs such as eyes. The main goal of this research is to investigate whether two potential excipients, namely: p-coumaric acid and benzophenone-4, affect the photodegradation, phototoxicity and photogenotoxicity of water solutions of four fluoroquinolones: ciprofloxacin, lomefloxacin, fleroxacin and clinafloxacin. We conducted a set of bioassays combined with the application of high-performance liquid chromatography and mass spectrometry techniques. The significant reduction of phototoxic and photogenotoxic abilities was evaluated in mixtures with ciprofloxacin and p-coumaric acid by using the umu test with Salmonella typhimurium TA1535/pSK1002, the methylthiazol tetrazolium reduction assay, and the micronucleus assay with the V79 cell line. In the bacterial assay the opposite effect was observed for the formulation with lomefloxacin and p-coumaric acid. This may be explained by the significant differences in the profile of the lomefloxacin photodegradation products. Further, the photoprotective and antiphotomutagenic abilities of ciprofloxacin mixed with benzophenone-4 were assessed. Promising results obtained in compositions with ciprofloxacin may be a basis for further research. Nevertheless, the increase in the DNA damage potential in mixtures with p-coumaric acid and two other antibiotics shows the importance of the safety evaluation of such innovative combinations.

Spectroscopic and Molecular Modeling Studies on Binding of Fleroxacin with Human Serum Albumin.

Fleroxacin (FLRX) is a new member of the class of fluoroquinolones, its effects on human serum albumin (HSA) and the mechanism of action are poorly understood, Especially, the secondary structural alterations of HSA induced by FLRX and the inner filter effect, which resulted in a spurious decrease in the observed fluorescence intensity and affected the binding parameters calculated from it are not considered. In this paper, binding of FLRX to HSA has been studied using multi-spectroscopy and molecular modeling methods. Fluorescence spectra revealed that the observed fluorescence quenching of HSA by FLRX was due to a 1∶1 complex formation by a static quenching process with a constant of 105 L·mol-1. The thermodynamic parameters (ΔH and ΔS) were calculated to be -107.99 kJ·mol-1 and -240.99 J·mol-1·K-1 via the Van't Hoff equation, which indicated that hydrogen bond and van der Waals force were the dominant intermolecular force. From the synchronous fluorescence, FT-IR and three dimensional fluorescence spectra, it was evident that the binding of FLRX to HSA induced a conformational change in the protein, and the alterations of secondary structure were quantitatively calculated by the evidence from FTIR spectra with reductions of α-helices of about 18.3%, decreases of ß-sheet structures of about 9.6%, and increases of ß-turn structures of about 18.0%. Site marker competitive experiments showed that phenylbutazone and FLRX shared a common binding site Ⅰ corresponding to the subdomain Ⅱ A of HSA. The binding details between FLRX and HSA were further confirmed by molecular docking studies, which revealed that FLRX was bound at subdomain Ⅱ A through multiple interactions, such as hydrogen bond, hydrophobic and van der Waals, etc. The accurate and full basic data in the work is beneficial to clarify the binding mechanism of FLRX with HSA and is helpful for understanding its effect on protein function during the blood transportation process.

Synthesis, structure, and biological evaluation of a copper(ii) complex with fleroxacin and 1,10-phenanthroline.

A novel mixed-ligand Cu(ii) complex combined with the quinolone drug fleroxacin and 1,10-phenanthroline was synthesized in this work. The crystal structure of the complex was characterized via X-ray crystallography, which was the first reported single crystal complex of fleroxacin. Results showed that Cu(ii) was coordinated through pyridone oxygen and one carboxylate oxygen atom of fleroxacin, as well as two nitrogen atoms from 1,10-phenanthroline. Various characterization methods, including Fourier transform infrared, elementary analysis, thermogravimetry, and X-ray powder diffraction, were applied. The Cu(ii)-quinolone complex exhibited favorable biological activities, and was proved to be capable of transforming supercoiled PUC19 DNA into nicked form under hydrolytic conditions. The obtained pseudo-Michaelis-Menten kinetic parameter was 12.64 h(-1), which corresponded to a million-fold rate enhancement in DNA cleavage. In addition, the interaction capacity of the complex with human serum albumin (HSA) was investigated. The results demonstrated a moderately intense combination between HSA and the complex. The complex evidently quenched the fluorescence of HSA. Approximately 19.2% of the quenching was attributed to Förster resonance energy transfer (FRET), whereas the rest was caused by ground-state complex formation (molar ratio of HSA : complex = 1 : 2). The energy of the complex was excited during FRET, which increased the fluorescence of the complex by approximately 18%.

Fluoroquinolones impair tendon healing in a rat rotator cuff repair model: a preliminary study.

BACKGROUND: Recent studies suggest that fluoroquinolone antibiotics predispose tendons to tendinopathy and/or rupture. However, no investigations on the reparative capacity of tendons exposed to fluoroquinolones have been conducted. HYPOTHESIS: Fluoroquinolone-treated animals will have inferior biochemical, histological, and biomechanical properties at the healing tendon-bone enthesis compared with controls. STUDY DESIGN: Controlled laboratory study. METHODS: Ninety-two rats underwent rotator cuff repair and were randomly assigned to 1 of 4 groups: (1) preoperative (Preop), whereby animals received fleroxacin for 1 week preoperatively; (2) pre- and postoperative (Pre/Postop), whereby animals received fleroxacin for 1 week preoperatively and for 2 weeks postoperatively; (3) postoperative (Postop), whereby animals received fleroxacin for 2 weeks postoperatively; and (4) control, whereby animals received vehicle for 1 week preoperatively and for 2 weeks postoperatively. Rats were euthanized at 2 weeks postoperatively for biochemical, histological, and biomechanical analysis. All data were expressed as mean ± standard error of the mean (SEM). Statistical comparisons were performed using either 1-way or 2-way ANOVA, with P < .05 considered significant. RESULTS: Reverse transcriptase quantitative polymerase chain reaction (RTqPCR) analysis revealed a 30-fold increase in expression of matrix metalloproteinase (MMP)-3, a 7-fold increase in MMP-13, and a 4-fold increase in tissue inhibitor of metalloproteinases (TIMP)-1 in the Pre/Postop group compared with the other groups. The appearance of the healing enthesis in all treated animals was qualitatively different than that in controls. The tendons were friable and atrophic. All 3 treated groups showed significantly less fibrocartilage and poorly organized collagen at the healing enthesis compared with control animals. There was a significant difference in the mode of failure, with treated animals demonstrating an intrasubstance failure of the supraspinatus tendon during testing. In contrast, only 1 of 10 control samples failed within the tendon substance. The healing enthesis of the Pre/Postop group displayed significantly reduced ultimate load to failure compared with the Preop, Postop, and control groups. There was no significant difference in load to failure in the Preop group compared with the Postop group. Pre/Postop animals demonstrated significantly reduced cross-sectional area compared with the Postop and control groups. There was also a significant reduction in area between the Preop and control groups. CONCLUSION: In this preliminary study, fluoroquinolone treatment negatively influenced tendon healing. CLINICAL RELEVANCE: These findings indicate that there was an active but inadequate repair response that has potential clinical implications for patients who are exposed to fluoroquinolones before tendon repair surgery.

Intramolecular charge transfer effects on the diradical character and second hyperpolarizabilities of open-shell singlet X-π-X (X = donor/acceptor) systems.

We investigate the effect of the quadrupole-type intramolecular charge transfer (ICT) in open-shell singlet donor-π-donor (D-π-D) molecules on the singlet open-shell (diradical) character and the longitudinal second hyperpolarizabilities γ (the third-order nonlinear optical (NLO) properties at the molecular scale). For this investigation we used the para-quinodimethane (PQM) with point charges (pc's) model calculated with the unrestricted coupled cluster method including single and double excitations with a perturbative treatment of the triple excitations (UCCSD(T)). In this model, the diradical character y and the amount of the ICT, that is, the D-π-D nature, can be varied primarily by changing the exocyclic carbon-carbon bond (C-C) lengths and the external pc's Q, respectively. It turns out that the increase in the D-π-D nature decreases the y values, moves the y values (ymax) giving the maximum γ (γmax) to the large y region, and enhances the γmax values, for example, the γmax of the singlet diradical PQM with Q = -2.8 au reaches twice that of the singlet diradical PQM without any pc's. This result indicates that open-shell singlet D-π-D systems with ICT are promising candidates for a new class of third-order NLO molecules, whose γ values are more enhanced than those of conventional closed-shell D-π-D systems and of symmetric open-shell singlet systems without the ICT. To confirm this tendency, we examine the boron-disubstituted PQM dianion model, which is found to exhibit further enhancement of γ as compared to the PQM model with intermediate diradical character due to the synergy effects of the intermediate open-shell singlet nature and the strong field-induced ICT nature in the dianionic state of the D-π-D system. Further investigation of the acceptor-π-acceptor (A-π-A) type ICT effect in the PQM-pc model shows that both D-π-D and A-π-A type symmetric ICTs give similar effects on the relationship between y and γ, though there are some differences originating in the orbital contraction and extension induced by the pc's. The present results contribute to understanding the third-order NLO properties of open-shell symmetric ICT systems and thus to constructing new design guidelines for highly efficient third-order NLO systems.

Pressure-dependent relaxation in the photoexcited mott insulator ET-F2TCNQ: influence of hopping and correlations on quasiparticle recombination rates.

We measure the ultrafast recombination of photoexcited quasiparticles (holon-doublon pairs) in the one dimensional Mott insulator ET-F(2)TCNQ as a function of external pressure, which is used to tune the electronic structure. At each pressure value, we first fit the static optical properties and extract the electronic bandwidth t and the intersite correlation energy V. We then measure the recombination times as a function of pressure, and we correlate them with the corresponding microscopic parameters. We find that the recombination times scale differently than for metals and semiconductors. A fit to our data based on the time-dependent extended Hubbard Hamiltonian suggests that the competition between local recombination and delocalization of the Mott-Hubbard exciton dictates the efficiency of the recombination.