The recent advance and prospect of natural source compounds for the treatment of heart failure.

Heart failure is a continuously developing syndrome of cardiac insufficiency caused by diseases, which becomes a major disease endangering human health as well as one of the main causes of death in patients with cardiovascular diseases. The occurrence of heart failure is related to hemodynamic abnormalities, neuroendocrine hormones, myocardial damage, myocardial remodeling etc, lead to the clinical manifestations including dyspnea, fatigue and fluid retention with complex pathophysiological mechanisms. Currently available drugs such as cardiac glycoside, diuretic, angiotensin-converting enzyme inhibitor, vasodilator and ß receptor blocker etc are widely used for the treatment of heart failure. In particular, natural products and related active ingredients have the characteristics of mild efficacy, low toxicity, multi-target comprehensive efficacy, and have obvious advantages in restoring cardiac function, reducing energy disorder and improving quality of life. In this review, we mainly focus on the recent advance including mechanisms and active ingredients of natural products for the treatment of heart failure, which will provide the inspiration for the development of more potent clinical drugs against heart failure.

Natural products as the calcium channel blockers for the treatment of arrhythmia: Advance and prospect.

Arrhythmia is one of the commonly heart diseases with observed abnormal heart-beat rhythm that caused by the obstacles of cardiac activity and conduction. The arrhythmic pathogenesis is complex and capricious and related with other cardiovascular diseases that may lead to heart failure and sudden death. In particular, calcium overload is recognized as the main reason causing arrhythmia through inducing apoptosis in cardiomyocytes. Moreover, calcium channel blockers have been widely used as the routine drugs for the treatment of arrhythmia, but the different arrhythmic complications and adverse effects limit their further applications and demand new drug discovery. Natural products have always been the rich minerals for the development of new drugs that could be employed as the versatile player for the discovery of safe and effective anti-arrhythmia drugs with new mechanisms. In this review, we summarized natural products with the activity against calcium signaling and the relevant mechanism of actions. We are expected to provide an inspiration for the pharmaceutical chemists to develop more potent calcium channel blockers for the treatment of arrhythmia.

Design and photoelectric properties of D-A-π-A carbazole dyes with different π-spacers and acceptors for use in solar cells: a DFT and TD-DFT investigation.

Density functional theory (DFT) and time-dependent DFT (TD-DFT) were used to calculate the properties of the carbazole dyes TYZ-1 to TYZ-5, which differed in their π-spacers. The carbazole dyes TYZ-6 and TYZ-7 were then designed; these were based on TYZ-3 (which had 2,2':5',2″-terthiophene as its π-spacer) but had more strongly electron-withdrawing second acceptor groups than TYZ-3. All of these dyes except for TYZ-5 presented quasi-planar conformations, and the calculated energies of their highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) molecular orbitals as well as their HOMO-LUMO gaps (Eg) suggest that these dyes are suitable for use as sensitizers. Lengthening the π-spacer and increasing its degree of conjugation were found to cause the absorption spectrum of the dye to redshift and to facilitate hole injection. The Eg values of TYZ-6 and TYZ-7 were calculated to be smaller than that of TYZ-3 due to the weaker electron-withdrawing power of the second acceptor group in TYZ-3, and the dyes TYZ-2, TYZ-3, TYZ-6, and TYZ-7 presented the smallest Eg values. Local electron excitations following UV-vis absorption led to electronic transitions, particularly HOMO to LUMO transitions (> 94.3% of all transitions). The excited states of these dyes were found to have quasi-planar conformations, although their dihedral angles were smaller than those in the corresponding ground states. The Stokes Shifts calculated for the seven dyes (which ranged from 51.9 to 98.1 nm) suggested that self-absorption was unlikely to occur. Overall, the calculations indicated that the dyes TYZ-2, TYZ-3, TYZ-6, and TYZ-7 are promising candidates for use in dye-sensitized solar cells.

From Graphene to Carbon Nanotubes: Variation of the Electronic States and Nonlinear Optical Responses.

From the same piece of graphene sheet, (3, 3) and (6, 0) carbon nanotube clips were obtained on the basis of the different manners of rolling. The nature of the electronic state varies differently with different manners of rolling and is significantly affected by zigzag edges. The intermediate structures formed during the rolling process were functionalized with fluorine and oxygen atoms to investigate the electronic states and nonlinear optical (NLO) responses. Passivation of the intermediate structures with fluorine neither changes the nature of electronic states and nor improves the NLO responses. In constrast, passivation with oxygen enhances the NLO properties and changes the electronic states of the structures upon passivating at the open zigzag edges.

Computational design of two-photon fluorescent probes for intracellular free zinc ions.

Two-photon fluorescence probes used in two-photon fluorescence microscopy (TPM) can achieve intact tissue imaging without destruction. Therefore, for a long time, TPM has been an important tool in biology and medicine. In this background via a quantum chemical method, a series of zinc ion probe molecules using N,N-di(2-picolyl)ethylenediamine (DPEN) as the recognition group were studied, which are based on the photoinduced electron transfer (PET) mechanism. The fact that the one-photon absorption peak is almost unchanged and the fluorescence emission intensity increased significantly upon coordination with a zinc ion reveals that these probes can be PET fluorescent bioimaging reagents. And it is predicted that when the chemically modified probe molecule is incorporated with Zn(2+), the two-photon absorption (TPA) cross-section (δmax) will greatly increase and the TPA peak will be in the near-infrared region. The molecules after changing the fluorophore become more suitable for probing Zn(2+) in vivo, and a modification at the end of the fluorophore can fine-tune the fluorescence and TPA properties. The detailed investigations will provide a theoretical basis for synthesizing new zinc-ion-responsive two-photon fluorescent probes.

Computational design of two-photon fluorescent probes for a zinc ion based on a Salen ligand.

A two-photon fluorescent probe has become a critical tool in biology and medicine owing to its capability of imaging intact tissue for a long period of time, such as in two-photon fluorescence microscopy (TPM). In this context, a series of Salen-based zinc-ion bioimaging reagents that were designed based on an intramolecular charge-transfer mechanism were studied through the quantum-chemical method. The increase of one-photon absorption and fluorescence emission wavelength and the reduction of the oscillator strength upon coordination with a zinc ion reveal that they are fluorescent bioimaging reagents used for ratiometric detection. When the Salen ligand is incorporated with Zn(2+), the value of the two-photon absorption (TPA) cross-section (δmax) will decrease, and most of the ligands and complexes exhibit a TPA peak in the near-infrared spectral region. That is, a substituent at the end of the ligand can influence the luminescence property, besides increasing solubility. In addition, the effect of an end-substituted position on the TPA property was considered, such as ortho and meta substitution. The detailed investigations will provide a theoretical basis to synthesize zinc-ion-responsive two-photon fluorescent bioimaging reagents as powerful tools for TPM and biological detection in vivo.

A theoretical investigation of two typical two-photon pH fluorescent probes.

Intracellular pH plays an important role in many cellular events, such as cell growth, endocytosis, cell adhesion and so on. Some pH fluorescent probes have been reported, but most of them are one-photon fluorescent probes, studies about two-photon fluorescent probes are very rare. In this work, the geometrical structure, electronic structure and one-photon properties of a series of two-photon pH fluorescent probes have been theoretically studied by using density functional theory (DFT) method. Their two-photon absorption (TPA) properties are calculated using the method of ZINDO/sum-over-states method. Two types of two-photon pH fluorescent probes have been investigated by theoretical methods. The mechanisms of the Photoinduced Charge Transfer (PCT) probes and the Photoinduced Electron Transfer (PET) probes are verified specifically. Some designed strategies of good two-photon pH fluorescent probes are suggested on the basis of the investigated results of two mechanisms. For the PCT probes, substituting a stronger electron-donating group for the terminal methoxyl group is an advisable choice to increase the TPA cross section. For the PET probes, the TPA cross sections increase upon protonation.

Nonlinear optical properties for a class of hexa-peri-hexabenzocoronene chromophores: a computational investigation.

The systematic investigation of the linear and nonlinear optical properties on such a class of hexa-peri-hexabenzocoronene (HBC) chromophores is of significance for rationally designing two-photon absorption (TPA) materials. The results indicate that increasing the strength of electron-donating or accepting terminal groups leads to bathochromic-shift of the absorption band and enhancement of the TPA cross section (δ(max)). For the molecules with fluorinated methylene and cyano substituents, replacement of a double bond by a triple bond in the conjugated linker produces the increase of δ(max), owing to the lower bond-length alternation and better rigidity of phenylene-ethynylene. In contrast, for the molecules with nitro groups, the similar replacement results in a slight decrease of δ(max) because N-HBC-E-NO2 has excellent planarity architecture and effective electronic coupling. The TPA spectra are red-shifted and the δ(max) values are enhanced as the number of branches increases. Thus, a solvatochromism effect has a positive influence on the TPA response of the nitryl compounds due to larger polarization of the nitro moiety. We have shed light on the linear relationship between the first hyperpolarizability and δ(max). These HBC derivatives hold potential as high-performance nonlinear optical materials.

Theoretical insight into linear optical and two-photon absorption properties for a series of N-arylpyrrole-based dyes.

N-arylpyrrole-based dyes possessing excellent opto-electronic properties are promising candidates for two-photon fluorescence labeling materials. The systematic investigation of novel N-arylpyrrole derivatives is of great importance for both fine-tuning electronic spectra and designing two-photon absorption (2PA) materials. We thoroughly studied influences of the π-conjugated center and N-substituted pyrrole moieties on the linear optical and 2PA properties. Our results show that introducing N-arylpyrrole produces bathochromic-shifts of the absorption and emission bands and an enhancement of the 2PA cross section (δ(max)), demonstrating that the electron-rich pyrrole moieties can efficiently increase intramolecular charge transfer. Substitution of fluorenyl with benzothiadiazole produces the lower energy gap, higher emission lifetime, red-shift of 2PA spectra and larger δ(max). The absorption and emission bands are highly dependent on the nature of the active building blocks. The aromatic rings attached to pyrrole can modulate the absorption peaks in the high energy and thus subtly modify the electronic properties.

Computational study of the electronic structures, UV-Vis spectra and static second-order nonlinear optical susceptibilities of macrocyclic thiophene derivatives.

Using thiophene (which has a moderate resonance energy) as a spacer rather than benzene permits better π-electron delocalization and leads to a large nonlinear optical response. Thus, the nonlinear optical coefficients of a series of macrocyclic thiophene derivatives (C[3T_DA](n) with C(n) symmetry) were studied, and their electronic structures, UV-Vis spectra and static second-order nonlinear optical susceptibilities (ß(0)) were computed. The calculated results showed that ΔE(H-L) increased and the UV-Vis spectrum redshifted as the number of C[3T_DA] units increased (one C[3T_DA] unit consists of trithiophene and diacetylene). The value of ß(0) calculated by either the ZINDO-SOS or the FF method showed the same trend: the absolute value of ß(0) increased as the number of units increased. The value of ß(0) predicted by ZINDO-SOS was an order of magnitude larger than that predicted by the FF method. However, the results suggest that macrocyclic thiophene compounds potentially exhibit large static second-order nonlinear optical susceptibilities.

Theoretical investigation of the two-photon absorption properties of 3,6-bis(4-vinylpyridinium) carbazole derivatives--new biological fluorescent probes.

The present study focuses on a series of carbazole derivatives, which are being investigated as potential two-photon fluorescent probes (TFP) for DNA detection and two-photon bioimaging. The geometric structures, electronic structures, and the one-photon (OPA) and two-photon (TPA) absorption properties of 3,6-bis(1-methyl-4-vinylpyridinium) carbazole (BMVC) derivatives, as well as their dications and diiodized derivatives, were studied using density functional theory (DFT) and Zerner's intermediate neglect of differential overlap (ZINDO) method. The results showed that the TPA spectra of the diiodized BMVC derivatives and their dications are all found in the near-infrared region (NIR). At the same time, the diiodized BMVC derivatives presented larger TPA cross-sections than the neutral BMVC derivatives and the dications. These theoretically derived values were also in good agreement with their corresponding experimentally observed values, and they indicated that the diiodized BMVC may be the form of this TFP that combines with DNA. The diiodized BMVC derivatives and the dications have the potential to be excellent TPA materials, especially when used as TFPs in nucleic acid imaging applications.

Theoretical prediction of one- and two-photon absorption properties of N-annulated quaterrylenes as near-infrared chromophores.

Graphene nanoribbons (GNRs) have attracted increasing attention due to high potentiality in nanoelectronics. In the present study, quantum-chemical calculations of structural and nonlinear optical properties have been first carried out for the nanoelectronical materials, a new series of ladder-type N-annulated quaterrylenes and their imide chromophores. The effects of the solvent, terminal groups, the number of N-annulated bridges, and π-conjugated length are discussed in detail. The solvent effect is significant on the one-photon absorption (OPA). Moreover, the OPA and two-photon absorption (TPA) properties of the two series of DI and N-MI molecules show a clear solvent dependence, which is attributed to the carboximide substitution featuring larger polarization. Introducing electron-donating groups and dicarboximides and increasing the conjugated length lead to red-shifts of the OPA, emission, and TPA spectra, lower emission lifetimes, and enhanced TPA cross sections (δ(max)), but further extension of the conjugated framework does not always promote an increase of δ(max). The changing trends of δ(max) can be explained by the transition moment and the intramolecular charge transfer. All N-annulated quaterrylene and their imide derivatives possess small energy gaps, intense near-infrared absorption and emission, and large δ(max), which are important for use as two-photon fluorescent labeling materials.

A comparative study of one- and two-photon absorption properties of pyrene and perylene diimide derivatives.

Two important classes of organic molecules, perylene diimide (PDI) and pyrene derivatives have been found to possess relatively excellent photophysical and photochemical properties and especially high two-photon absorption cross sections (δ(T)(max)). Herein, one-photon absorption (OPA) and two-photon absorption (TPA) properties of some novel PDI and pyrene derivatives were comparatively investigated by the density functional theory (DFT) and Zerner's intermediate neglect of differential overlap (ZINDO) methods. The calculated results indicate that with respect to PDI derivatives, the maximum TPA cross-sections for pyrene compounds increase obviously, the maximum peaks of OPA and TPA spectra are blue-shifted, the ΔE(H-L) (energy gaps between the highest occupied orbital and the lowest unoccupied orbital) increase. The different π-conjugated bridges (fluorene and pyrene) and terminal groups have slight effect on the OPA properties. Nevertheless, the molecules bearing 1,6-disubstituted pyrene as the π-conjugated bridge display the largest δ(T)(max) in both series of compounds 3 and 4. Moreover, the δ(T)(max) values of molecules with benzothiazole-substituted terminal groups are larger than those of the molecules with diphenylamine, which is attributed to benzothiazole groups stabilizing the planarity of the branch parts, extending the conjugated length and increasing the π-electron delocalized extent. Furthermore, the molecular size has marked effect on OPA and TPA properties. It is worthy to mention that cruciform 8 displays the largest δ(T)(max) among all the studied molecules in the range of 600-1100 nm. This research could provide a better understanding for the origin of the linear and nonlinear optical properties, and it would be helpful to gain more information about designing two-photon absorption materials with large δ(T)(max).

A time-dependent density functional theory investigation on the origin of red chemiluminescence.

Is the resonance-based anionic keto form of oxyluciferin the chemical origin of multicolor bioluminescence? Can it modulate green into red luminescence? There is as yet no definitive answer from experiment or theory. The resonance-based anionic keto forms of oxyluciferin have been proposed as a cause of multicolor bioluminescence in the firefly. We model the possible structures by adding sodium or ammonium cations and investigating the ground- and excited-state geometries as well as the electronic absorption and emission spectra. A role for the resonance structures is obvious in the gas phase. The absorption and emission spectra of the two structures are quite different--one in the blue and another in the red. The differences in the spectra of the models are small in aqueous solution, with all the absorption and emission spectra in the yellow-green region. The resonance-based anionic keto form of oxyluciferin may be one origin of the red-shifted luminescence but is not the exclusive explanation for the variation from green (approximately 530 nm) to red (approximately 635 nm). We study the geometries, absorption, and emission spectra of the possible protonated compounds of keto(-1) in the excited states. A new emitter keto(-1)'-H is considered.

Theoretical study of solvent effect on one- and two-photon absorption properties of starburst DCM derivatives.

The equilibrium geometries, electronic structures, one-photon absorption (OPA) and two-photon absorption (TPA) properties of starburst 4-(dicyanomethylene)-2-methyl-6-[p-(dimethylamino)styryl]-4H-pyran (DCM) derivatives have been studied by using density functional theory (DFT) and Zerner's intermediate neglect of differential overlap (ZINDO) program. Results showed that increasing the number of branches in DCM molecules and introducing stronger electron withdrawing groups are efficient ways to enhance the TPA cross sections. For the two- and three-branched molecules of the DCM derivatives, the solvent effect on the OPA and TPA properties was also considered by adapting the self-consistent reaction field (SCRF) theory with the polarizable continuum model (PCM) to model the interaction with the solvent in ZINDO program. The calculated molecular structure, transition dipole moment and intramolecular charge transfer (ICT) in different solvents have been analyzed to approximate how the solvent affects the TPA cross section. Results indicated that the TPA cross section increases as the polarity of the solvents increases, and it reaches a maximum when the dielectric constant epsilon equals 20.7.

Theoretical study on photophysical properties of ambipolar spirobifluorene derivatives as efficient blue-light-emitting materials.

The aim of this work is to provide an in-depth interpretation of the optical and electronic properties of a series of spirobifluorene derivatives. These materials show great potential for application in organic light-emitting diodes as efficient blue-light-emitting materials due to the tuning of the optical and electronic properties by the use of different electron donors (D) and electron acceptors (A). The geometric and electronic structures of the molecules in the ground state are studied with density functional theory (DFT) and ab initio HF, whereas the lowest singlet excited states are optimized by ab initio CIS. The energies of the lowest singlet excited states are calculated by employing time-dependent density functional theory (TD-DFT). The results show that the HOMOs, LUMOs, energy gaps, ionization potentials, electron affinities, reorganization energies, and exciton binding energies for these complexes are affected by different D and A moieties. Also, it has obtained that these blue-light-emitting materials have improved charge transport rate and charge transfer balance performance and can be used as efficient ambipolar-transporting materials in organic light-emitting diodes.

Theoretical investigation of one- and two-photon absorption properties of platinum acetylide chromophores.

In this paper, we have theoretically investigated bis((4-phenylethynyl)phenyl) ethynyl)bis(trimethylphosphine)platinum(II) (PE2) and its analogs three platinum acetylide complexes (1-3) that feature highly pi-conjugated ligands (alkynyl-dimethylfluorene substituted with electron-donating or -withdrawing moieties). The geometrical and electronic structures are calculated at the ECP60MWB//6-31G*(H, C, P, N, S) basis set level by the density functional theory (DFT) method; one-photon absorption properties have been calculated by using time-dependent DFT (TDDFT) and Zerner's intermediate neglect of differential overlap (ZINDO) methods, and two-photon absorption (TPA) properties are obtained with the ZINDO/sum-over-states method. The values of beta(sp) and beta(d) for Pt are adjusted to -1 eV and -28.5 eV, respectively, to make one-photon absorption spectra calculated by ZINDO closest to the experimental data and TDDFT results. The calculated results indicate that all molecules in this work (involving cis isomers of molecules 1-3) take on two TPA peaks in the 600-800 nm region. The peak at 700-750 nm should not be simply attributed to the appearance of noncentrosymmetric cis isomers in solution, although trans and cis isomers adhere to a different selection rule. Every TPA peak results from its transition character. Molecules 1-3 show greater two-photon absorption strength compared with PE2 and retain good transparency.

Theoretical study on structural, electronic, and optical properties of ambipolar diphenylamino end-capped oligofluorenylthiophenes and fluoroarene-thiophene as light-emitting materials.

Ambipolar diphenylamino end-capped oligofluorenylthiophenes and fluoroarene-thiophene show great potential for application in organic light-emitting diodes (OLEDs). Here, we provide an in-depth investigation on the optical and electronic properties of OF(2)TP-NPh ( 1a), OF(2)DTP-NPh ( 2a), OF(2)TTP-NPh ( 3a), OF(2)QTP-NPh ( 4a), and 2,5-bis-(2,3,5,6-tetrafluoro-4-trifluoromethyl-phenyl)-2,2':5',2'':5'',2'''-quaterthiophene ( 5a). The geometric and electronic structures of the oligomers in the ground-state are studied with density functional theory (DFT) and ab initio Hartree-Fock, whereas the lowest singlet excited states are optimized by ab initio CIS. The energies of the lowest singlet excited states are calculated by employing time-dependent density functional theory (TDDFT). The results show that the highest occupied molecular orbitals, lowest unoccupied molecular orbitals, energy gaps, ionization potentials, and electron affinities for the oligomers are affected by the thiophene chain length and the different end-caps. The absorption and emission spectra exhibit red shifts to some extent due to the increasing thiophene chain length and the enhancing electron-donating property of the end-caps. Furthermore, the large Stokes shifts ranging from 58 to 80 nm are examined, resulting from a more planar conformation of the excited-state between the two adjacent units in the oligomers. All the calculated data show that the fluoroarene-thiophene has improved electron transport rate and charge transfer balance performance, and all the studied molecules can be used as ambipolar-transporting materials in OLEDs.

Theoretical study on photophysical properties of multifunctional electroluminescent molecules with different pi-conjugated bridges.

The photophysics of a series of molecular organic light-emitting diodes (OLEDs) has been studied by theoretical calculation. These molecular OLEDs have been integrated by an electron- and hole-transporting components as well as an emitting components into the donor-pi-acceptor (D-pi-A) structures: 2-carbazolyl-7-dimesitylboryl-9,9-diethylfluorene (1), trans-4'-N-carbazolyl-4-dimesitylborylstilbene (2), and trans-2-[(4'-N-carbazolyl)styryl]-5-dimesitylborylthiophene (3). To reveal the relationship between the structures and properties of these multifunctional electroluminescent materials, the ground- and excited-state geometries were optimized at the B3LYP/6-31G(d), HF/6-31G(d), and CIS/6-31G(d) levels, respectively. The ionization potentials and electron affinities were computed. The mobilities of hole and electron in these compounds were studied computationally based on the Marcus electron transfer theory. The lowest excitation energies (E(g)) and the maximum absorption and emission wavelengths of these compounds were calculated by time-dependent density functional theory methods. The solvent effect on the emission spectra of these compounds was considered by a polarizable continuum model. As a result of these calculations, it was concluded that the electron injections of these compounds are much easier than Mes(2)B[p-4,4'-biphenyl-NPh(1-naphthyl)], and the diethylfluorene-based compound has higher electron mobility and better equilibrium properties as compared to the stilbene-based and styrylthiophene-based compounds.

Color-tuning mechanism in firefly luminescence: theoretical studies on fluorescence of oxyluciferin in aqueous solution using time dependent density functional theory.

The first singlet excited state geometries of various isomers and tautomers of firefly oxyluciferin (OxyLH2), as well as their fluorescence spectra in aqueous solution, were studied using time dependent density functional theory (TDDFT). With changing pH in aqueous solution, three fluorescence peaks, blue (450 nm), yellow-green(560 nm), and red (620 nm) correspond to neutral keto and enolic forms, the monoanionic enolic form,and the monocationic keto form respectively. A counterion, Na+, was predicted to cause a blue shift in the fluorescence of anionic OxyLH2. The contributions of a charge transfer (CT) state upon electronic excitation of the planar and twisted structures were predicted. CT was large for the twisted structures but small for the planar ones. The differences between pK and pK* of various oxyluciferin species were predicted using a Forster cycle. A new possible light emitter, namely, the monocation keto form (keto+1), was considered.