Semiquinone Radical Anion Research Articles

Binding Modes in Metal Ion Complexes of Quinones and Semiquinone Radical Anions: Electron‐Transfer Reactivity

9,10-Phenanthrenequinone (PQ) and 1,10-phenanthroline-5,6-dione (PTQ) form 1:1 and 2:1 complexes with metal ions (M (n+)=Sc (3+), Y (3+), Mg (2+), and Ca (2+)) in acetonitrile (MeCN), respectively. The binding constants of PQ--M (n+) complexes vary depending on either the Lewis acidity or ion radius of metal ions. The one-electron reduced species (PTQ(-)) forms 1:1 complexes with M (n+), and PQ(-) also forms 1:1 complexes with Sc(3+), Mg(2+), and Ca(2+), whereas PQ(-) forms 1:2 complexes with Y(3+) and La(3+), as indicated by electron spin resonance (ESR) measurements. On the other hand, semiquinone radical anions (Q(-) and NQ(-)) derived from p-benzoquinone (Q) and 1,4-naphthoquinone (NQ) form Sc(3+)-bridged pi-dimer radical anion complexes, Q(-)--(Sc(3+))(n)--Q and NQ(-)--(Sc(3+))(n)-NQ (n=2 and 3), respectively. The one-electron reduction potentials of quinones (PQ, PTQ, and Q) are largely positively shifted in the presence of M (n+). The rate constant of electron transfer from CoTPP (TPP(2-)=dianion of tetraphenylporphyrin) to PQ increases with increasing the concentration of Sc(3+) to reach a constant value, when all PQ molecules form the 1:1 complex with Sc(3+). Rates of electron transfer from 10,10'-dimethyl-9,9'-biacridine [(AcrH)(2)] to PTQ are also accelerated significantly by the presence of Sc(3+), Y(3+), and Mg(2+), exhibiting a first-order dependence with respect to concentrations of metal ions. In contrast to the case of o-quinones, unusually high kinetic orders are observed for rates of Sc(3+)-promoted electron transfer from tris(2-phenylpyridine)iridium(III) [Ir(ppy)(3)] to p-quinones (Q): second-order dependence on concentration of Q, and second- and third-order dependence on concentration of Sc(3+) due to formation of highly ordered radical anion complexes, Q()--(Sc(3+))(n)--Q (n=2 and 3).

Molecular Mechanical Devices Based on Quinone−Pyrrole and Quinone−Indole Dyads: A Computational Study

A set of intramolecularly connected dyads consisting of a quinone unit and a pyrrole or indole moiety have been designed and evaluated in quantum-chemical calculations. It is shown computationally for several systems, depending on the length and attachment points of the interconnecting chains, that a reduction of the quinone to the semiquinone radical anion or quinolate dianion state leads to a reversible intramolecular reorientation from a pi-stacked to a T-stacked arrangement. In the rearranged structures, a hydrogen bond from the pyrrole or indole N-H function to the semiquinone or quinolate pi-system is created upon reduction. In some systems, hydrogen bonds to the semiquinone or quinolate oxygen atoms are partly feasible and will be preferred over T-stacking. The choice of systems has been based on recent computational observations related to photosystem I. Systems with pyrrole or indole units should provide a better basis for the envisioned molecular motor than recently proposed quinone-benzene dyads. The intramolecular interactions modify the quinone redox potentials. Electronic g-tensors have been computed for the semiquinone states. These reflect characteristically the presence and nature of hydrogen bonds to the semiquinone and represent suitable electron paramagnetic resonance spectroscopic probes for the preferred structures. Intramolecular proton transfer is possible in the dianionic state.

Photoreactions of p-Quinones with Dimethyl Sulfide and Dimethyl Sulfoxide in Aqueous Acetonitrile†

The effects of dimethyl sulfide (DMS) and dimethyl sulfoxide (DMSO) on the photoreactions of 1,4-benzoquinone (BQ), 1,4-naphthoquinone (NQ), 9,10-anthraquinone (AQ) and several derivatives in acetonitrile/water were studied. The observed triplet state of the quinones is quenched and the rate constant is close to the diffusion-controlled limit for reactions of most quinones with DMS and lower with DMSO. Semiquinone radical anions (Q*-) produced by electron transfer from sulfur to the triplet quinone were detected. For both DMS and DMSO the yield of Q*- is similar, being generally low for BQ and NQ, substantial for AQ and largest for chloranil. The specific quencher concentrations and the effects of quinone structure and redox potentials on the time-resolved photochemical properties are discussed.

Thermochromism of Metal Ion Complexes of Semiquinone Radical Anions. Control of Equilibria between Diamagnetic and Paramagnetic Species by Lewis Acids

Metal ion complexes of semiquinone radical anions exhibit different types of thermochromism depending on metal ions and quinones. Metal ion complexes of 1,10-phenanthroline-5,6-dione radical anion (PTQ(.-)) produced by the electron-transfer reduction of PTQ by 1,1'-dimethylferrocene (Me(2)Fc) in the presence of metal ions (Mg(2+) and Sc(3+)) exhibit the color change depending on temperature, accompanied by the concomitant change in the ESR signal intensity. In the case of Mg(2+), electron transfer from Me(2)Fc to PTQ is in equilibrium, when the concentration of the PTQ(.-)-Mg(2+) complex (lambda(max) = 486 nm) increases with increasing temperature because of the positive enthalpy for the electron-transfer equilibrium. In contrast to the case of Mg(2+), electron transfer from Me(2)Fc to PTQ is complete in the presence of Sc(3+), which is a much stronger Lewis acid than Mg(2+), to produce the PTQ(.-)-Sc(3+) complex (lambda(max) = 631 nm). This complex is in disproportionation equilibrium and the concentration of the PTQ(.-)-Sc(3+) complex increases with decreasing temperature because of the negative enthalpy for the proportionation direction, resulting in the remarkable color change in the visible region. On the other hand, the p-benzosemiquinone radical anion (Q(.-)) forms a 2:2 pi-dimer radical anion complex [Q(.-)-(Sc(3+))(2)-Q] with Q and Sc(3+) ions at 298 K (yellow color), which is converted to a 2:3 pi-dimer radical anion complex [Q(.-)-(Sc(3+))(3)-Q] with a strong absorption band at lambda(max) = 604 nm (blue color) when the temperature is lowered to 203 K. The change in the number of binding Sc(3+) ions depending on temperature also results in the remarkable color change, associated with the change in the ESR spectra.

Non-enzymatic oxidation of NADH by quinones

Non-enzymatic oxidation of NADH by a large number of different quinones has been explored both theoretically and experimentally. It is concluded that the smaller benzo- and naphtho-quinones are capable of oxidising NADH in aqueous solution, whereas the larger anthraquinone is not. The mechanisms of stepwise electron and proton transfers are explored, and ruled out in favour of direct hydride transfer. For menadione (2-methyl-1,4-naphthoquinone), no reaction is observed experimentally; theoretically we find that there is a very close balance between the energetic cost of hydride removal from NADH and the energy gain of formation of the menadione semiquinone radical anion.

Conformation-driven and semiquinone-gated proton-pump mechanism in the NADH-ubiquinone oxidoreductase (complex I)

A novel mechanism for proton/electron transfer is proposed for NADH-quinone oxidoreductase (complex I) based on the following findings: (1) EPR signals of the protein-bound fast-relaxing semiquinone anion radicals (abbreviated as Q Nf - ) are observable only in the presence of proton-transmembrane electrochemical potential; (2) Iron–sulfur cluster N2 and Q Nf - are directly spin-coupled; and (3) The projection of the interspin vector extends only 5 Å along the membrane normal [Yano, T., Dunham, W.R. and Ohnishi, T. (2005) Biochemistry, 44, 1744–1754]. We propose that the proton pump is operated by redox-driven conformational changes of the quinone binding protein. In the input state, semiquinone is reduced to quinol, acquiring two protons from the N (matrix) side of the mitochondrial inner membrane and an electron from the low potential (NADH) side of the respiratory chain. A conformational change brings the protons into position for release at the P (inter-membrane space) side of the membrane via a proton-well. Concomitantly, an electron is donated to the quinone pool at the high potential side of the coupling site. The system then returns to the original state to repeat the cycle. This hypothesis provides a useful frame work for further investigation of the mechanism of proton translocation in complex I.

Hypoxia-selective activation of 5-fluorodeoxyuridine prodrug possessing indolequinone structure: radiolytic reduction and cytotoxicity characteristics

We synthesized a 5-fluorodeoxyuridine ( 5-FdUrd) derivative possessing an indolequinone structure ( IQ-FdUrd) to characterize the radiolytic reduction in aqueous solution and the radiation-activated cytotoxicity against EMT6/KU cells under hypoxic conditions. IQ-FdUrd released antitumor agent 5-FdUrd upon hypoxic, but not aerobic, irradiation with the G value of 0.38 × 10 −7 mol J −1. Laser flash photolysis of IQ-FdUrd in Ar-purged aqueous solution with dimethylaniline as an electron donor gave rise to a transient absorption spectrum characteristic of semiquinone radical anion, which decayed via second order kinetics. It is most likely that bimolecular disproportionation of intermediate semiquinone radicals occurs to release 5-FdUrd. IQ-FdUrd showed enhanced cytotoxicity against EMT6/KU cells in a radiation dose-dependent manner upon hypoxic irradiation. IQ-FdUrd is potentially a prototype compound for new class of radiation-activated antitumor prodrugs that are useful for radiation treatment of hypoxic tumors.

New long-wavelength ethanolamino-substituted hypocrellin: photodynamic activity and toxicity to MGC803 cancer cell

To improve hydrophilicity and photoactivity of the new type of therapeutic agent, hypocrellin, a novel long-wavelength ethanolamino-substituted hypocrellin B (EAHB) was synthesized and its molecular structure was characterized by IR, NMR, MS, and UV–vis spectrometers, and EAHB had strong absorption at the phototherapeutic window (600–900 nm). Illumination of deoxygenated DMSO solution containing EAHB generated a strong electron paramagnetic resonance (EPR) signal, which was assigned to the semiquinone anion radical of EAHB (EAHB − ). Absorption measurements displayed that the absorptive bands at 632 and 565 nm (shoulder) arose from the semiquinone anion radical (EAHB − ) and the absorptive bands at 519 and 450 nm (shoulder) belonged to hydroquinone (EAHBH 2), which were formed via the decay of EAHB − in water-contained solution. Superoxide anion radical (O 2 − ) was produced via electron transfer from EAHB − (the precursor) to ground state oxygen. The presence of NADH, a bio-electron donor, significantly enhanced production of EAHB − and O 2 − . Singlet oxygen O 2 ( 1Δ g) could be produced via energy transfer from triplet EAHB to ground state oxygen molecules. The quantum yield of O 2 ( 1Δ g) and the relative quantum yield of O 2 − of EAHB were 0.15 and 0.76, respectively, with the parent compound hypocrellin B (HB) as the standard. It was inferred that Type I pathway was possibly a major photodynamic mechanism of EAHB. The study on photobiological action of EAHB on MGC803 cancer cells revealed that EAHB kept the same good phototoxic ability as HB but reduced 4 times cytotoxicity than HB, and also its photopotentiation factor increased 4-folds.

EPR characteristics of heat treated complexes of metals with demineralised humic brown coal in air and ammonia atmospheres

Investigations were carried out on complexes of metal ions with solvent pre-extracted and demineralised Lubstow humic brown coal (HC) ( Eocene, Midlands Poland; content of humic acids above 80%). Metal–humic brown coal complexes (HC–M) were obtained at pH 5.1 by ion exchange of solid HC with the following metal ions: Mg 2+, Ca 2+, Ba 2+, Ti 3+, Cr 3+, Mn 2+, Fe 3+, Co 2+, Ni 2+, Cu 2+, Ag +1, Zn 2+, Cd 2+, Al 3+, Ga 3+, Tl 3+, Sn 2+, Pb 2+, and Bi 3+. Metal uptake by the HC is dependent on the radius of the metal ion and its susceptibility to complexation in polyfunctionalised humic matrix. The complexes were heat treated to different final temperatures in a range up to 650 °C. Raw HC–M complexes and resultant chars were characterised by elemental composition, IR, and quantitative electron paramagnetic resonance spectroscopy (QEPR). The binding sites of the metal cations are oxygen functional groups (mainly –COOH, –OH phenolic). EPR parameters (i.e., concentration of stable free radicals and g-value) were determined in air and gaseous ammonia atmosphere. The nature of the observed free radicals in raw HC–M complexes is mainly of semiquinone type ( g=2.0036 in air and 2.0045 in gaseous ammonia atmosphere). Heat treatment of the complexes causes gradual defunctionalisation, resulting in elimination of quinone and hydroquinone structural units and generation of polyaromatic sheets containing aromatic type free radicals. Practically complete disappearance of semiquinone radicals occurs at 400 °C heat treatment, and intensive development of aromatic type free radicals occurs above that temperature. Paramagnetic metal ions cause strong decrease of the observed free radical concentration in HC–M complexes due to antiferromagnetic interaction with electrons of semiquinone type radicals (Cu 2+>Fe 3+>Mn 2+>Cr 3+>Ti 3+). The observed concentration of free radicals in the HC–M complexes with alkaline metal ions of s and p block metals as well as d 10 metal ions is higher compared to the value of uncomplexed HC. Gaseous ammonia strongly shifts hydroquinone–semiquinone–quinone equilibria towards generation of semiquinone anion radicals, which is manifested by elevated concentrations of free radicals and increases of g-value in chars of heat treated samples in the region below 400 °C. The control of free radical types and concentrations in environment allows to: (i) predict the state of temporal alkalinity (due to use of ammonia and urea based fertilisers), (ii) binding of heavy metal cations, and (iii) degree of humic matter maturation.

Syntheses, Structures, and Properties of Quinone-Bridged Calix[6]arenes

Abstract The quinone-bridged calix[6]arenes 1 and 2, carrying a 1,4-benzoquinone moiety in the cavity of a calixarene macrocycle, were synthesized from the corresponding p-methoxyphenol derivatives. X-ray crystallography revealed the structures of 1 and 2, in which the quinone moiety is located inside the cone-shaped calix[6]arene framework and surrounded by the lower-rim substituents. Their 1H NMR spectra showed upfield shifts of the protons on the bridging unit in comparison with reference compounds without the calixarene framework, in accordance with their crystal structures. The cyclic voltammograms of 1 and 2 showed two waves, the second ones being considerably broadened. Their reduction potentials were found to be negatively shifted in comparison with those of the reference compounds. These shifts were explained in terms of the nonbonded interaction between the ether oxygen atoms of the calixarene moiety and the quinone moiety, as well as the sterically restricted access of the counter cation to the semiquinone anion radical. Reactions of 1 with hydroxylamine and phenylhydrazine afforded the corresponding hydroquinone along with the quinone monoimine derivatives, indicating that electron transfer from the amines proceeds quickly, although the negatively shifted reduction potentials of 1 are apparently unfavorable for the electron transfer process.

Theoretical study on the photophysical and photochemical characteristics of aluminum ion-complexed perylenequinone

The photophysical and photochemical characteristics of the aluminum ion-complexed perylenequinone (Al 3+-PQ) at different chain length have been explored employing the quantum chemical method in this paper. It is revealed firstly, the optimized structures of the complexes at different chain lengths are all one-dimension polymeric chains in the ground state. Secondly, the chelation reaction not only decreases the molecular E HOMO, E LUMO and Δ E, but also shifts the excitation spectra bathochromatically. In addition, based on the present calculation results, the first triplet excitation energy of the complexes at different chain length can directly be transferred to molecular oxygen to generate the singlet excited molecular oxygen ( 1O 2) (Type II). On the contrary, the semiquinone anion radicals (Al 3+-PQ −) cannot react with triplet molecular oxygen to form the superoxide anion radical (O 2 −), which indicates photosensitization mechanism Type I is not involved in the photodynamic action of Al 3+-PQ.

Remarkable Accelerating Effects of Ammonium Cations on Electron-Transfer Reactions of Quinones by Hydrogen Bonding with Semiquinone Radical Anions

Remarkable accelerating effects of the ammonium cation (NH4+) have been observed on photoinduced electron-transfer reactions from the triplet excited state of tetraphenylporphyin (H2P) to quinones [p-benzoquinone (Q) and naphthoquinone (NQ)] in dimethyl sulfoxide (DMSO). The tetrabutylammonium cation (NBu4+) is also effective to accelerate the electron-transfer reduction of Q and NQ in dichloromethane (CH2Cl2). The hydrogen bonding interaction between the semiquinone radical anion (Q•- or NQ•-) and NH4+ was confirmed by the ESR spectra of the Q•-/NH4+ and Q•-/(NH4+)2 [NQ•-/NH4+ and NQ•-/(NH4+)2] complexes in DMSO. Accelerating effects of NH4+ in DMSO and NBu4+ in CH2Cl2 on the rates of photoinduced electron-transfer reduction of Q by H2P result from the positive shift of the Ered value of quinones together with a constant Eox value of H2P determined from cyclic voltammetry measurements. The driving force dependence of the rate constants for photoinduced electron-transfer reduction of quinones in the presence of various concentrations of ammonium cations was evaluated in light of the Marcus theory of electron transfer.

The photosensitization activity of a water-soluble carboxylate of hypocrellin B

Based on theoretical prediction of the molecular polarity, water-soluble sodium HB-14-carboxylate (SCHB) was prepared and its photosensitization activity was evaluated. SCHB shows not only very good amphiphilicity but also much stronger absorption at 620 nm than its parents. In DMSO–PBS (3:1 by volume) solution (pH 7.4) of SCHB, the photosensitization generated the semiquinone anion radicals (SCHB − ) under anaerobic condition or superoxide anion radicals (O 2 − ) in the presence of oxygen. In the oxygenated PBS solution of SCHB, hydroxyl radicals ( OH) were photogenerated. In addition, SCHB could also be photosensitized to generate singlet oxygen ( 1O 2) with a quantum yield about 0.26. These findings suggest that SCHB can exert photodynamic action via photosensitization.

Behavior of the semiquinone anion radical of hypocrellin B produced by electrolysis in dimethylsulfoxide

The behavior of the semiquinone anion radical of hypocrellin B (HB), produced by electrolysis, has been studied by cyclic voltammetry, steady-state electron spin resonance, timeresolved electron spin resonance and in situ UV-Vis spectra. The results showed that the formation mechanisms of HB —· were different between electrolysis and photolysis, and the disproportionation of semiquinone anion radical of HB (HB —· ) could not occur in dimethylsulfoxide; on the contrary, a syn -proportionation reaction in which HB 2— reacts with HB to form HB —· was observed experimentally. At the same time, the kinetic parameters of HB —· were obtained from the time-decay experiments of HB —· .

Evolution from Hydrogen Bond to Proton Transfer Pathways in the Electroreduction of α-NH-Quinones in Acetonitrile

On the basis of voltammetric behaviors obtained for the electrochemical reduction of a series of α-NH-quinones (Q) of increasing basicity (5H-benzo[b]carbazole-6,11-dione (BCD), 2-{[4′-(trifluoromethyl)phenyl]amine}-1,4-naphthalenedione 2-(phenylamine)-1,4-naphthalenedione (PAN), 2-[(4′-methoxyphenyl)amine]-1,4-naphthalenedione (p-MeOPAN), and 2,5-di(α-methylbenzylamine)-1,4-benzoquinone (DMeBABQ)), in the presence of additives with increasing acidity [ethanol (EtOH), phenol(PhOH), benzoic acid (HBz), perchloric acid it was possible to identify some of the species present in the diffusion kinetic layer, allowing to control the protonation steps and/or hydrogen bond formation prior to and/or following the electron transfer processes. EtOH and PhOH act as hydrogen bonding donors with the corresponding semiquinone radical anion, and dianion hydroquinone, electrogenerated species. Due to the low acidity level of EtOH, the hydrogen bonding association process was detected only for meanwhile, with PhOH a strong hydrogen bonding process was detected, even at 0.3 equivalents of PhOH. The diagrams of average number of “ligands” vs. log [EtOH]/[Q] for and complexes were constructed using the successive association constants obtained from the experimental half-wave potential displacements. These diagrams show that the maximum number of molecules of EtOH hydrogen bonded to and directly depends on the basicity of the corresponding quinone. With HBz, the voltamperometric behavior shows the direct protonation of the electrogenerated provoking a typical electrochemical-chemical-electrochemical mechanism, with “the chemical step” being a proton transfer. Finally, the use of a completely dissociated acid in acetonitrile solution, allowed to observe the successive interaction of protons with each of the different species appearing in the quinone/hydroquinone systems, including mono- and di-protonation of the neutral quinones. © 2004 The Electrochemical Society. All rights reserved.

Solvent effects on g-tensors of semiquinone radical anions: polarizable continuum versus cluster models

Density functional theory has been applied to study environmental effects on electronic g-tensors of a series of 1,4 semiquinone radical anions. In particular, solvent effects on solute structure, spin density distribution, and g-tensor have been investigated using both the conductor-like polarizable continuum model (CPCM) and explicit cluster solvent models. For protic solvents, the CPCM calculations provide solvent effects in qualitative but not in quantitative agreement with experiment. Explicit inclusion of solvent molecules hydrogen-bonded to the semiquinone oxygen atoms is required to obtain a more quantitative description. Available experimental g-tensor data in aprotic solvents are insufficient to judge adequately the performance of the CPCM calculations. However, the present data should serve to calibrate future experimental electron paramagnetic resonance studies. Detailed molecular-orbital analyses of the solvent influences on the g-tensors of various semiquinone radical anions are provided.

Electronic g-Tensors of Semiquinones in Photosynthetic Reaction Centers. A Density Functional Study

A recently developed density functional (DFT) approach for the calculation of electronic g-tensors has been applied to semiquinone radical anions in the different protein environments of photosynthetic reaction centers. Supermolecular models have been constructed, based on combined crystallographic and quantum chemical structure data, for the QA and QB active sites of bacterial reaction centers, for the A1 site of photosystem I, as well as for ubisemiquinone in frozen 2-propanol. After scaling of the computed Δgx components by 0.92, both Δgx and Δgy components computed at gradient-corrected DFT level with accurate spin−orbit operators agree with high-field EPR reference data essentially to within experimental accuracy in all four systems studied. The influence of the various semiquinone−protein noncovalent interactions has been studied by successive removal of individual residues from the models. The effects of hydrogen bonding to the two carbonyl oxygen atoms of the semiquinones are nonadditive, due to c...

A novel amphiphilic 2-taurine substituted hypocrellin B (THB) and its photodynamic activity

A novel 2-taurine substituted hypocrellin B (THB) was designed and synthesized in this work. Both the light absorbance in the phototherapeutic window (600–900 nm) and the amphiphilicity (a compromise between the lipophilicity and hydrophilicity) were greatly improved. The semiquinone anion radical (THB˙−), superoxide anion (O2˙−), hydroxyl radical (˙OH) (Type I mechanism) and singlet oxygen (1O2) (Type II mechanism) could be generated via the photosensitization of THB, confirming its photosensitization activity. In this work, it was also found that the cytochrome c reduction method is not the exclusive one for detecting O2˙− in photosensitization systems.

Thermochromism of the disproportionation equilibrium of pi-dimer radical anion complexes bridged by scandium ions.

Semiquinone radical anion (Q(*-)) forms a stable pi-dimer with neutral p-benzoquinone (Q), bridged by two or three scandium ions (Sc(3+)) to afford Q(*-)-nSc(3+)-Q (n= 2,3), which is in disproportionation equilibrium with Q and hydroquinone (QH(2)). The number of binding scandium ions changes depending on temperature, causing a remarkable color change associated with the change in the ESR spectra.

Photogeneration of the free radicals and singlet oxygen by chrysophanol from rheum

In the current work, chryosphanol (MHAQ) was isolated and purified from rheum, and the photosensitization activities were studied. In nitrogen-saturated DMSO solution, irradiation of chryosphanol (MHAQ) with visible light (＞430 nm) produced the semiquinone radical anions (MHAQ • − ), which was intensified significantly by an electron donor NADH, suggesting electron transfer between the excited and ground state photosensitizer molecules. In an air-saturated DMSO solution, superoxide radical anions (O 2 • − ), trapped by DMPO, were detected. It was proved that O 2 • − was not originated from the singlet oxygen ( 1 O 2 ) but dependent on DMPO, chrysophanol, oxygen and the irradiation time. The singlet oxygen and • OH could also be produced by the photosensitization of the photosensitizer. These suggest that chrysophanol possesses the photosensitization activity via Type I mechanism and Type II mechanism. To evaluate the photosensitization activities of MHAQ, emodin and mixed anthraquinone derivatives extracted from rheum, the relative productivities of O 2 • − were estimated to be 1.8, 1.1 and 1.0 respectively and the quantum yields for singlet oxygen to be 0.36, 0.53 and 0.14 respectively. Therefore, these low-cost pigments may be potentially used as phototherapeutic medicine for some kind of vascular diseases or photo-activated pesticides.