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Photodynamic therapy (PDT) has been extensively studied as a noninvasive treatment option; however, the current PDT agents are often restricted with poor solubility, difficult accumulation in tumor sites, low singlet oxygen yield and low penetration depth.

A prismatic Ru8Pd4 type metal-organic cage ( rac - MOC-52 ) was assembled from polypyridine bipodal metalloligand [Ru(bpy)2(qpy)(BF4)2] (qpy=4,4′:2′,2′′:4′′,4′′′-quaterpyridine; bpy=2,2′-Bipyridine) with Pd(II) salt. The spatial structures of the MOCs were determined by X-ray single crystal diffraction. It was found that the outer configuration of the MOCs was similar to a cubic barrel deficient of upper and lower surfaces. Furthermore, pure chiral precursor Δ / Λ -[Ru(bpy)2]2+ was obtained through pre-resolution method. And then pure chiral metalloligand Δ / Λ- Ruqpy and metal-organic cages Δ / Λ- MOC-52 were successfully obtained by stepwise assembly strategy. The one-photon, two-photon luminescence, and emission enhancement of rac - MOC-52 by sodium tetraphenylborate guest, as well as the properties of circular dichroism and circularly polarized luminescence of Δ / Λ- MOC-52 were investigated.

An Ir8Pd4-heteronuclear metal-organic cage (MOC-51) was assembled from bipodal metalloligand [Ir(ppy)2(qpy)(BF4)] (qpy = 4,4′:2′,2″:4″,4‴-quaterpyridine; ppy = 2-phenylpridine) with Pd(II) salt. The cubic barrel shaped MOC shows one-photon and two-photon excited deep-red emission, as well as large singlet oxygen quantum yields under visible light irradiation, therefore exhibiting great potentials in organelles-targeted cell imaging and photodynamic therapy (PDT). Compared with the Ir(III) metalloligand, the Ir8Pd4-MOC showed less dark toxicity and higher mitochondria-targeting efficiency. The localization in mitochondria overcomes the limitation of short lifetime and diffusion distance of ROS in cell, thus improved PDT effect can be obtained in low light dose usage of the MOC. This study presents the first case of Ir-based metal-organic cages for bio-applications in successful integration of imaging diagnosis and photodynamic therapy

Five cyclometalated Ir(III) complexes with high phosphorescence efficiencies have been synthesized from 1,3-bis(1-propyl-1H-benzo[d]imidazol-2-yl)benzene (Pro-MBImB) or 2-(2,4-Difluorophenyl)pyridine (Fppy) based ligands with different ancillary ligands. It was found that these complexes have a wide range of emitting wavelength, covering the whole visible region, with moderately long lifetime (81–2159 ns) and high quantum yield (75–89%). Especially, the introduction of electron withdrawing −COOEt group onto the ancillary ligand extends the emission wavelength and affords good red-light emitting properties, and the obtained CIE (Commission Internationale de L'Eclairage) coordinates of (0.69, 0.31) in complex 2 are close to the standard red light and approaching near infrared region.

Five transition metal coordination polymers, {[Cu(4-pmntd)2(NO3)2]∙2CHCl3}n (1), {[Cu(4-pmntd)2(NO3)2]·3C7H8}n (2), {[Cu(4-pmntd)2(CF3SO3)(H2O)]·CF3SO3·H2O·CH3OH}n (3), [Cd(4-pmntd)2]n·nSiF6·x(CH3OH)·y(CHCl3) (4), and [Zn(4-pmntd)2(CF3SO3)2]n·x(solvent) (5), have been obtained from a ditopic ligand, N,N'-bis(4-pyridylmethyl)naphthalene diimide (4-pmntd). Either sql- or dia- structures are generated from four connecting coordination nodes of the metal centers. While delicate interpenetration and structural tuning in these complexes is achieved by the different conformations and spatially extending geometries adopted by the ligand and “secondary building process” induced by pillar-like anions.

This paper proposes a sustainable method to prepare glutaric acid from glucose via an α-keto glutaric acid derived from glucose by fermentation using Corynebacterium glutamicum GKGA. Glutaric acid was prepared from α-keto glutaric acid via the hydrogenation of a 1,3-dithiolane diamide intermediate as the key step. The combination of biotransformation and chemical transformation of glutaric acid provided an efficient and environment-friendly method for the sustainable synthesis of glutaric acid

Two series of isostructural lanthanide coordination complexes, namely, LIFM-42(Ln) (Ln=Eu, Tb, Gd, in which LIFM stands for the Lehn Institute of Functional Materials) and LIFM-43(Ln) (Ln=Er, Yb), were synthesized through the self-assembly of an excited-state intramolecular proton transfer (ESIPT) ligand, 5-[2-(5-fluoro-2-hydroxyphenyl)-4,5-bis(4-fluorophenyl)-1H-imidazol-1-yl]isophthalic acid (H2 hpi2cf), with different lanthanide ions. In the coordination structures linked by the ligands and oxo-bridged LnIII2 clusters (for LIFM-42(Ln) series) or isolated LnIII ions (for LIFM-43(Ln) series), the ESIPT ligand can serve as both the host and antenna for protecting and sensitizing the photoluminescence (PL) of LnIII ions. Meanwhile, the -OH⋅⋅⋅N active sites on the ligands are vacant, which provides availability to systematically explore the PL behavior of Ln complexes with ESIPT interference. Based on the accepting levels of different lanthanide ions, energy transfer can occur from the T1 (K*) or T1 (E*) (K*=excited keto form, E*=excited enol form) excited states of the ligand. Furthermore, the sensitized lanthanide luminescence in both visible and near-infrared regions, as well as the remaining K* emission of the ligand, can be modulated by the ESIPT responsiveness to different solvents, anions, and temperature.

A facilely available zwitterionic ligand, 1,1′-(1,4-phenylenebis(methylene))dipyridin-4(1H)-one (PBPO), has been designed to bear intraligand charge transfer (ILCT) energy states. PBPO was used to assemble two series of Ln(III) complexes with either 2D (6,3)-hcb network (LIFM-24(Ln), Ln = Pr, Nd, and Sm), or 1D loop-and-chain (LIFM-25(Ln), Ln = Eu, Gd, Tb, Dy, Ho, Er, Tm, and Yb) polymeric structures, as determined by the radius of the lanthanide ions. Highly efficient photoluminescence (PL) in the visible to near-infrared (NIR) regions can be obtained in these Ln-complexes, due to the extended energy transfer from both the triplet and ILCT states of the zwitterionic ligand. Among these complexes, LIFM-24(Pr) and LIFM-25(Dy) display excitation-dependent color tunable luminescence and white-light emission based on the combination of ligand-centered (LC) and metallic-centered (MC) emissions. Uniquely, a strict linear relationship was established between the excitation wavelength and the emission CIE (Commission Internationale de L'Eclairage) coordinates in a wide color range (orange to blue for LIFM-24(Pr), and yellow to blue for LIFM-25(Dy)), thereby providing prototype models for programmable PL color tuning and white-light emission, which are rarely achievable in homometallic Ln-complexes.

2D graphitic carbon nitride (g-C3N4) has attracted great attention as one of the rising-star candidates for prominent water-splitting photocatalysts. Here, we report an extremely facile one-step, template-free method to synthesize ultrathin g-C3N4 nanosheets (CN-UMF) by thermal polycondensation of urea simply covered with kitchen-available melamine foam (MF). Compared with g-C3N4 agglomerates (CN-U) prepared without the covering of MF, the as-synthesized CN-UMF has an average thickness of about 4.5 nm and an enlarged surface area of 150.3 m2 g−1, leading to enhanced visible light absorption and charge carrier separation abilities. Therefore, it is able to serve as an efficient water-splitting photocatalyst to result in an outstanding hydrogen production rate of 5498 μmol g−1 h−1. This work provides a new facile strategy for the scalable synthesis of 2D g-C3N4 photocatalysts and paves the way for batch and green production of other 2D materials with good performance.

Tripodal ligand triCB-NTB (4,4′,4″-(2,2′,2″-nitrilotris(methylene)tris(1H-benzo[d]imidazole -2,1-diyl)tris(methylene))tribenzoic acid) was applied to assemble Pb(II) or Cd(II) coordination complexes, resulting in single-component near white light emission.

Reactions of ZnCl2 with 4′-(2,4-disulfophenyl)-2,2′:6′2″-terpyridine (H2DSPT) result to two new compounds with formula, {[Zn(DSPT)(H2O)2]·2H2O}n (1) and {[Zn(DSPT)(H2O)2]·H2O}n (2), respectively. Compound 1 is a binuclear complex, whereas compound 2 is a mononuclear organozinc compound. The coordination compounds can be controllable synthesized by adjust the pH value. The thermal behavior of 1 was explored by TG and VT-PXRD, which indicated that it undergo crystal-to-crystal transformation manner. Both compounds 1 and 2 show weak luminescence in both solid state and water emulsions compared with H2DSPT. The luminescence intensity of compound 1 can strongly enhanced by the addition of diethylchlorophosphonate (DCP), but significant less influenced by dimethylmethylphosphonate (DMMP), diethylcyanophosphonate (DCNP) and other selected organophosphate, which make compound 1 has potential application on nerve-agent detection.

Baeckea frutescens is an aromatic shrub used as ornamentals and as food flavor spices in the southern part of P. R. China. Two novel C-methylated biflavonoids named baeckeins J (1) and K (2) were isolated from the roots of B. frutescens, which possessed the unique carbon skeleton conjugated of a flavonol and one isoflavanonol molecule via the linkages of C(2)–C(8*) and C(3)–O–C(7*). The structures of compounds 1 and 2 were elucidated by analysis of 1D- and 2D-NMR, and HR-ESI-MS spectral data, and the absolute configuration for chiral C-atoms C(2) and C(3) were assigned by CD spectrometry combined with quantum chemical calculations. In the bioassay, baeckeins J and K exhibited strong cytoprotective effects on H2O2-induced oxidative cell death in PC12 cells.

Solvothermal reactions of 2,3,5,6-tetra(2-pyridyl)pyrazine (tppz) and sodium azide with different cadmium salts including CdCl2·2.5H2O, Cd(NO3)2 and Cd(CH3COO)2·2H2O at 80 °C produce three new coordination polymers, namely, {[Cd2(N3)2(tppz)Cl2]·2H2O}n (1), [Cd2(N3)2(tppz)(NO3)2]n (2) and {[Cd2(N3)2(tppz)(CH3COO)2]·2H2O}n (3), respectively. Single-crystal X-ray diffraction analysis reveals that the anions of the Cd(II) salts all participate in coordination in compounds 1–3. Compound 1 features an infinite one-dimensional (1D) chain with loops-and-rods topology, compound 2 exhibits a 1D ladder-like chain, while compound 3 possesses a 2D honeycomb-like network structure with (6,3) topology. The low-dimensional structures of compounds 1–3 are further stabilized by diverse supramolecular interactions such as hydrogen bonds and π⋯π stacking. Interestingly, when the temperature is increased to 100 °C, similar reactions of tppz and sodium azide ligands with CdCl2·2.5H2O, Cd(NO3)2 and Cd(CH3COO)2·2H2O lead to three other novel 3D Cd(II) coordination polymers formulated as [Cd3(N3)6(tppz)]n (4), {[Cd2(N3)2(tppz)(NO3)2]·MeOH}n (5) and [Cd4(N3)6(tppz)(CH3COO)2]n (6), respectively. The anions of the Cd(II) salts again take part in coordination in compounds 5 and 6 but disappear in the final structure of 4. Compound 4 displays a rare sxd-type 3D framework with the Schlafli symbol of (33·46·55·6) if each V-shaped trinuclear [Cd3(μ1,1-N3)4] secondary building unit (SBU) is regarded as a 6-connected node. In compound 5, both the Cd1 and Cd2 atoms serve as 3-connected nodes to construct an uncommon binodal (3,3)-connected 3D framework with (6·102)(62·10) topology. Compound 6 contains another type of V-shaped trinuclear [Cd3(μ1,1-N3)2(μ3-CH3COO)] SBU, which acts as a 7-connected node to fabricate a unique uninodal 7-connected 3D framework with a completely new topology of (36·42·510·63). The present results reveal that both anions and temperature play essential roles in the structural and topological diversity of such six new Cd(II) coordination polymers. Moreover, the IR spectra, thermogravimetric analysis curves, and solid-state luminescence properties of all the compounds have been also investigated. Compared with the free tppz ligand, compounds 1–6 exhibit superior luminescence properties with largely enhanced emission, indicating that they may be good candidates for optical materials.

Nine new coordination compounds, namely, [Co(HDSPTP)2(H2O)4]·4H2O (H2DSPTP=4’-(2,4-disulfophenyl)-3,2’:6’3”-terpyridine, 1 and 2), {[Ni(DSPTP)(H2O)4]·3H2O}n (3), {[Cu(HDSPTP)2(H2O)3]·8H2O}n (4), {[Cu(HDSPTP)2(H2O)3]·6H2O}n (5), {[Cu(DSPTP)(H2O)2]·H2O}n (6), {[Zn(DSPTP)(H2O)2]·2H2O}n (7), {[Cd(DSPTP)(H2O)2]·2H2O}n (8), and [Ag2(DSPTP)(H2O)]n (9), were constructed based on a new ligand containing both terpyridyl and sulfo groups. The reactions of H2DSPTP with Co(NO3)2.6H2O resulted in two mononuclear complexes (compounds 1 and 2). They are polymorphisms that display different hydrogen bonding networks. They are selectively synthesized by altering the added alkalis. The reaction of H2DSPTP with Ni(NO3)2·6H2O resulted in a 1D “S-shaped” coordination chain (compound 3). The reactions of Cu(II) with H2DSPTP at different pH value resulted in the following three compounds: two kinds of 1D chains obtained at pH 3.0 and 4.0 for compounds 4 and 5, respectively, and a 3D framework based on binuclear ring units with 4-connected sra topology (Compound 6). The reactions of H2DSPTP with ds-block ions resulted in the following three compounds: a Zn(II) (compound 7) and a Cd(II) (compound 8) 3D frameworks with structures similar to that in compound 6, and a 3D framework based on tetranuclear Ag(I) SBUs with binodal (4,8)-connected flu type 3D framework topology. The structural diversity is mainly attributed to the rich coordination modes (from monodentate to µ7-mode) and conformations (cis–cis and cis–trans) of HDSPTP−/DSPTP2− ligands and the metal center and can be controllable synthesized by altering the alkalis, and pH value. Thermal stability of all compounds was performed, and the thermal behaviors of compounds 6 and 8 were further explored by PXRD. Compound 6 exhibits low thermal stability and undergo a crystalline–crystalline-amorphous phase transition as temperature increases from 25 °C to 200 °C, and show amorphous–crystalline phase transition when rehydrated. However, compound 8 exhibits high thermal stability above 500 °C. Its crystalline phase can retain above 300 °C and undergo a crystalline–crystalline phase transition as temperature increased to 400 °C, and transit back to compound 8 when rehydrated. Moreover, luminescence properties of compounds 7–9 were also investigated.

The semi-dry flue gas desulfurization technology is widely used by coal-fired power plant. Desulfurization ash produced by semi-dry flue gas desulfurization, which consist CaSO3, CaCO3, Ca (OH) 2, CaSO4 and so on. It will bring new environment pollution if not been disposed properly. Building material industry is the main field in terms of the comprehensive utilization of desulfurization ash. While hazardous elements especial S and Hg may be released in the condition of temperature changes in the process of desulfurization ash utilization, causing second environment pollution. Combined with the research achievement of preparing autoclaved brick before, the content of S and Hg in raw materials and autoclaved brick were studied during the thermal utilization process in this article. The thermal stability of calcium sulfite was analyzed by the chemical reagent calcium sulfite. The results shown that calcium sulfite only lost crystal water whether in oxygen or air when the temperature is below 450°C, calcium sulfite was completely oxidized to calcium sulfate when the temperature is 475 °C in oxygen or 515°C in air. The contents of S and Hg which existed in desulfurization ash were 7.03%wt and 460μg/kg, respectively. The contents of S and Hg in autoclaved brick which made by desulfurization ash mainly were 5.16%wt and 450μg/kg, respectively. The results shown that the content of elements S and Hg in raw materials and autoclaved brick were roughly the same, which indicated that S and Hg no escape in the process of preparing autoclaved brick. The research provided a certain references for the comprehensive utilization of semi-dry flue gas desulfurization ash in the condition of heat and humid.

Three coordination polymers, {[CdI(DBBA)]∙0.5H2O}n (1, DBBA = 3,5-di(1Hbenzo[d]imidazol-1-yl)benzoate), [Cd(DBBA)(CH3COO)]n (2) and [Cd(DBBA)2]n (3), were obtained through reactions between Cd(II) salts and 3,5-di(1H-benzo[d]imidazol-1-yl)benzoic acid under different pH conditions. Compounds 1 and 2 are 3-D frameworks with rtl topology based on different binuclear Cd(II) secondary building units. Compound 3 was formed at lower pH and showed a 1-D chain assembled with M2L2 ring units. Moreover, phase purities, thermal behaviors, and photoluminescent properties have also been investigated.

The effects of 1- O -ethyl-3-butylcyclohexanol (OEBC) on the in vitro skin permeation of ten model drugs with different physicochemical properties across excised rat skin were evaluated. The results showed that the addition of OEBC significantly improved the in vitro skin permeation of the model drugs compared with the control (without OEBC). To clarify the promoting mechanism of OEBC, a multiple regression analysis was employed. When the permeation study was performed without OEBC, the permeability coefficient was quantitatively predicted as a linear function of molecular weight (log MW) and their lipophilicity (partition coefficient of drugs between octanol and water (log K o/w )) with a sufficiently high correlation coefficient ( r =0.842). It was suggested that skin permeation of drugs without OEBC was explained as a function of diffusion of drugs through the skin and partitioning of drugs to the skin. Although OEBC was administered, the permeability coefficient of drugs cannot be predicted as a linear function of log MW and log K o/w ( r =0.572).

The effect of 35 newly synthesized O -ethylmenthol (MET) derivatives on percutaneous absorption of ketoprofen was investigated in rats. In order to understand the relationship between the structure of compounds and promoting activity (structure–activity relationship), an artificial neural network (ANN) was employed. In the in vivo percutaneous absorption study, male Wistar rats, weighing 160–180 g, were used. The apparent penetration rate ( R p ) was estimated based on a pharmacokinetic model with a constant rate of penetration through the skin after a lag time. As an index of the promoting activity of each compound, an enhancement factor (Ef), defined as follows, was used: Ef= R p (with enhancer)/ R p (without enhancer). An irritation evoked on rat skin was microscopically judged at the end of the in vivo percutaneous absorption experiment and evaluated as a total irritation score (TIS). Ef and TIS were selected as output variables to determine the ANN structure. Calculated log P , molecular weight, steric energy (SE), van der Waals area, van der Waals volume, dipole moment, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were used as factors to determine the structural nature of cyclohexanol derivatives. Among these parameters, log P , SE and LUMO significantly affected the prediction of Ef and TIS. The predicted values of Ef and TIS coincided well with in vivo percutaneous absorption experimental values. However, results observed with a linear regression method were poor compared with the ANN approach. The contribution index of log P was ≈50% in the prediction of Ef, suggesting that lipophilicity among physicochemical properties contributes most of the promoting activity of these compounds.

Menthol derivatives were synthesized and evaluated for their promoting activity on the percutaneous absorption of ketoprofen and skin irritation in vivo, choosing O-ethylmenthol (MET) as the mother compound. The compound having a C-3 positionned n-butyl group (1-O-ethyl-3-n-buthylcyclohexanol, OEBC) indicated the most promoting activity and caused relatively little skin irritation. In order to understand enhancement mechanism of OEBC an in vitro permeation study of ketoprofen was performed. The time course of the cumulative amounts of drug permeated through the rat skin exhibited a linear relation after an initial lag time. This was analyzed in membrane diffusion model and the diffusion and partition parameters of ketoprofen were estimated. Both parameters were remarkably enhanced when a hydrogel containing a small quantity of OEBC (0.5%) was applied. Furthermore, to clarify the site of action of OEBC, we also investigated in vitro permeation study of ketoprofen employing different skins of state, reversed skin and stratum corneum stripped skin. When OEBC was added to the hydrogels which were applied to the reversed and stripped skins, almost no changes of the flux were observed compared with the control (without OEBC). These results suggested that the site of action of OEBC was stratum corneum. Morphological changes of the stratum corneum surface were microscopically observed with 0-2% OEBC. The spaces between the stratum corneum cells treated with 0.5-2% OEBC became extended and the shape of each cell became clear. This may suggest that the site of action of OEBC was the intercellular of stratum corneum. Furthermore, an electron spin resonance study was performed to investigate the effect of OEBC on the intercellular lipid bilayer fluidity of the stratum corneum and the rotational correlation times were calculated. 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) were used as the spin label. In use of OEBC, the fluidity of TEMPO labeled the stratum corneum lipid increased as the addition of OEBC. The results suggested that OEBC promote the penetration of drugs by enhancing fluidity of the local lipid bilayers around TEMPO.

The inclusion compound of amylose and salicylic acid (SA) was prepared by a sealed temperature control method, and the formation of the inclusion compound was confirmed by IR spectrum and powder X-ray diffraction. The kinetic parameters of dissociation of amylose/SA compound were studied by the nonisothermal method which was defined as a relationship between the dissociation ratio and time. The values of activation energy (Ea) and frequency factors (InA) were calculated by a nonlinear least-square method. In this study, the formation of the inclusion compound of amylose/SA was confirmed by IR spectrum powder X-ray diffraction. SA existed in a molecule form in the spiral stouction of amylose. The dissociation of amylose/SA compound was attributed to first order reaction. The values of Ea calculated by the nor-isothermal method were 21.71 and 22.41 kJ x mol(-1) at heating rate 5 and 10 degrees C x h(-1), respectively. The corresponding isothermal method value of Ea was 22.17 kJ x mol(-1); the calculated InA values were 9.32 and 10.08 at heating rate 5 and 10 degrees C x h(-1), respectively. The corresponding isothermal method lnA value was 9.26. The results were in good agreement with Ea values and lnA values by isothermal method. These results indicated that the non-isothermal method described in this study could be adequately used for the stability study of inclusion compound and was a rapid and accurate method for the determination of kinetic parameters.

We collected and completely sequenced 28,469 full-length complementary DNA clones from Oryza sativa L. ssp. japonica cv. Nipponbare. Through homology searches of publicly available sequence data, we assigned tentative protein functions to 21,596 clones (75.86%). Mapping of the cDNA clones to genomic DNA revealed that there are 19,000 to 20,500 transcription units in the rice genome. Protein informatics analysis against the InterPro database revealed the existence of proteins presented in rice but not in Arabidopsis . Sixty-four percent of our cDNAs are homologous to Arabidopsis proteins.

The influence of the amounts of additives including 1-O-ethyl-3-n-butylcyclohexanol (OEBC), diisopropyl adipate (DIA), and isopropanol (IPA) on the penetration rate (Rp) of ketoprofen from hydrogels through rat skin in vivo was investigated. Skin irritation evoked by the application of hydrogels was evaluated based on a microscopic observation of skin cross-sections. Both optimization techniques incorporating an artificial neural network (ANN) and a second-order polynomial regression analysis were applied to the optimization of ketoprofen hydrogel formulations. Findings indicated that the Rp and total irritation score (TIS) of the skin were predicted quantitatively as a function of quantities of OEBC, DIA, and IPA, employing ANN. In contrast, the prediction ability of the polynomial regression equation was somewhat poorer compared with that of ANN. The observed results of Rp and TIS in the optimal formulation coincided well with the predictions in the simultaneous optimization technique incorporating ANN. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1004–1014, 2001

l -Menthol was selected as a lead compound to synthesize new candidates for percutaneous absorption enhancers. In a previous study, O -ethylmenthol (MET) was the most effective compound and caused relatively little skin irritation. To develop more effective compounds, mono- or disubstitute groups of cyclohexane with an O -ethyl group were synthesized. Some 35 compounds were synthesized and evaluated for their promoting activity and effect on skin. An in vivo percutaneous absorption study was performed using rats with hydrogel containing ketoprofen and each of the synthesized compounds. The plasma concentration of ketoprofen was determined after the application of hydrogel to the abdominal area of rats. The apparent penetration rate ( R p ) was estimated based on the pharmacokinetic model with a constant rate of penetration through the skin after the lag time. The 2-compartment model was applied to the data obtained from the iv administration. As an index to evaluate the promoting activity of each enhancer, an enhancement factor ( E f ) was defined as follows: E f = R p (with enhancer)/ R p (without enhancer). Irritation to skin was pathologically evaluated. The treated area of rat abdominal skin was exised after the in vivo experiment using total irritation score (TIS). The compound having a C-3 positioned iso -butyl group on the chemical structure was the most effective and caused relatively little irritation among mono-substituted compounds. In the case of di-substituted compounds, all had the same effect as or a stronger effect than MET. Furthermore, the promoting activity almost corresponded to irritation. To estimate log P , one of the physicochemical properties of molecules, a computer program ‘CAChe’ was employed. The log P was calculated using the atom typing scheme. Multiple regression analysis revealed that the relations between E f or TIS and log P were parabolic. It was suggested that the optimum log P value reflects the promoting activity to enhance percutaneous absorption of ketoprofen.