Related Articles

The title compound, [Cu2(C2O4)(C10H8N2)4](ClO4)2·2C3H7NO·H2O, contains doubly charged centrosymmetric dinuclear oxalato-bridged copper(II) complex cations, perchlorate anions, and DMF and water solvate mol­ecules. In the complex cation, the oxalate ligand is coordinated in a bis-bidentate bridging mode to the Cu atoms. Each Cu atom has a distorted tetra­gonal-bipyramidal environment, being coordinated by two N atoms of the two chelating bipy ligands and two O atoms of the doubly deprotonated oxalate anion. Pairs of perchlorate anions and water mol­ecules are linked into recta­ngles by O—H⋯O bonds in which the perchlorate O atoms act as acceptors and the water mol­ecules as donors. Methyl groups of the DMF solvent molecule are disordered over two sites with occupancies of 0.453 (7):0.547 (7), and the water molecule is half-occupied.

The title coordination polymer, {[MnCl(C18H14N4O)2(H2O)]Cl·C3H7NO·H2O}n, obtained by the solvothermal reaction of BIDPE and manganese(II) salt in H2O/DMF (DMF is dimethyl­formamide), is composed of a chain of [Mn2(BIDPE)2] [BIDPE is 1,1′-(oxydi-p-phenyl­ene)di-1H-imidazole] metallocyclic rings that exhibit inversion symmetry. The coordination about the Mn(II) ions is distorted octahedral with a MnClN4O coordination set. In the crystal, the polymeric chains are linked by O—H⋯Cl hydrogen bonds, forming a two-dimensional network parallel to (100). A number of C—H⋯Cl and C—H⋯O inter­actions are also present.

In the title compound, [Mn(C13H8N3O3)2]·C3H7NO·H2O, the metal atom is O,N,O′-chelated by two deprotonated Schiff bases and exists in a distorted octa­hedral geometry. The N–H groups, the carbonyl group of the DMF mol­ecule and the uncoord­inated water mol­ecule engage in N—H⋯O and O—H⋯O hydrogen-bonding inter­actions, generating a hydrogen-bonded ribbon that propagates along [110].

The metal atom of the title compound, [Zn(C13H8N3O2S)2]·C3H7NO·H2O, is O,N,O′-chelated by two deprotonated Schiff bases and it exists in a distorted octa­hedral geometry. The N–H groups of the ligands, the carbonyl group of the DMF mol­ecule and uncoordinated water mol­ecule engage in N—H⋯O and O—H⋯O inter­actions, generating a hydrogen-bonded ribbon that propagates along [110]. One thienyl ring is disordered over two positions in a 1:1 ratio.

Cutaneous drug reactions (CDRs) associated with sulfonamides are believed to be mediated through the formation of reactive metabolites that result in cellular toxicity and protein haptenation. We evaluated the bioactivation and toxicity of sulfamethoxazole (SMX) and dapsone (DDS) in normal human dermal fibroblasts (NHDF). Incubation of cells with DDS or its metabolite (D-NOH) resulted in protein haptenation readily detected by confocal microscopy and ELISA. While the metabolite of SMX (S-NOH) haptenated intracellular proteins, adducts were not evident in incubations with SMX. Cells expressed abundant N-acetyltransferase-1 (NAT1) mRNA and activity, but little NAT2 mRNA or activity. Neither NAT1 nor NAT2 protein were detectable. Incubation of NHDF with S-NOH or D-NOH increased reactive oxygen species formation and reduced glutathione content. NHDF were less susceptible to the cytotoxic effect of S-NOH and D-NOH than are keratinocytes. Our studies provide the novel observation that NHDF are able to acetylate both arylamine compounds and bioactivate the sulfone, DDS, giving rise to haptenated proteins. The reactive metabolites of SMX and DDS also provoke oxidative stress in these cells in a time- and concentration-dependent fashion. Further work is needed to determine the role of the observed toxicity in mediating CDRs observed with these agents.

The development of smart anti-cancer drugs that can selectively kill cancer cells while sparing the surrounding healthy tissues/cells unharmed is of paramount importance for safe and effective cancer therapy. We report a novel class of bifunctional compounds based on diarylidenylpiperidone (DAP) conjugated with an N-hydroxypyrroline (NOH, a nitroxide precursor) group. We hypothesized that the DAP would have cytotoxic (anti-cancer) activity, while the NOH moiety would function as a tissue-specific modulator (anti-oxidant) of cytotoxicity. The study used four DAPs, namely H-4073 and H-4318 without NOH and HO-3867 and HO-4200 with NOH substitution. The goal of the study was to evaluate the ‘proof-of-concept’ anticancer-versus-antioxidant efficacy of the DAPs using a number of cancerous (breast, colon, head and neck, liver, lung, ovarian, and prostate cancer) and noncancerous (smooth muscle, aortic endothelial, and ovarian surface epithelial cells) human cell lines. Cytotoxicity was determined using an MTT-based cell viability assay. All four compounds induced significant loss of cell viability in cancer cells, while HO-3867 and HO-4200 showed significantly less cytotoxicity in noncancerous cells. EPR measurements showed a metabolic conversion of the N-hydroxylamine function to nitroxide with significantly higher levels of the metabolite and superoxide radical-scavenging (antioxidant) activity in noncancerous cells when compared to cancer cells. Western-blot analysis showed that the DAP-induced growth arrest and apoptosis in cancer cells were mediated by inhibition of STAT3 phosphorylation at Tyr705 and Ser727 residues and induction of apoptotic markers of cleaved caspase-3 and PARP. The results suggest that the antioxidant-conjugated DAPs will be useful as a safe and effective anticancer agent for cancer therapy.

Background

A Noh mask worn by expert actors when performing on a Japanese traditional Noh drama is suggested to convey countless different facial expressions according to different angles of head/body orientation. The present study addressed the question of how different facial parts of a Noh mask, including the eyebrows, the eyes, and the mouth, may contribute to different emotional expressions. Both experimental situations of active creation and passive recognition of emotional facial expressions were introduced.

Methodology/Principal Findings

In Experiment 1, participants either created happy or sad facial expressions, or imitated a face that looked up or down, by actively changing each facial part of a Noh mask image presented on a computer screen. For an upward tilted mask, the eyebrows and the mouth shared common features with sad expressions, whereas the eyes with happy expressions. This contingency tended to be reversed for a downward tilted mask. Experiment 2 further examined which facial parts of a Noh mask are crucial in determining emotional expressions. Participants were exposed to the synthesized Noh mask images with different facial parts expressing different emotions. Results clearly revealed that participants primarily used the shape of the mouth in judging emotions. The facial images having the mouth of an upward/downward tilted Noh mask strongly tended to be evaluated as sad/happy, respectively.

Conclusions/Significance

The results suggest that Noh masks express chimeric emotional patterns, with different facial parts conveying different emotions This appears consistent with the principles of Noh which highly appreciate subtle and composite emotional expressions, as well as with the mysterious facial expressions observed in Western art. It was further demonstrated that the mouth serves as a diagnostic feature in characterizing the emotional expressions. This indicates the superiority of biologically-driven factors over the traditionally formulated performing styles when evaluating the emotions of the Noh masks.

The asymmetric unit of the title complex, [Ni(C12H8N2)3]S2O8·2C3H7NO·H2O, consists of a complex [Ni(phen)3]2+ cation and one isolated pds anion, with two DMF mol­ecules and one water mol­ecule as solvates (where phen is 1,10-phenanthroline, pds is the hexa­oxido-μ-peroxoido-di­sulf­ate dianion and DMF is dimethyl­formamide). The [Ni(phen)3]2+ cation is regular, with an almost ideal NiII bond-valence sum of 2.07 v.u. The group, as well as the water solvent mol­ecule, are well behaved in terms of crystallographic order, but the remaining three mol­ecules in the structure display different kinds of disorder, viz. the two DMF mol­ecules mimic a twofold splitting and the pds anion has both S atoms clamped at well-determined positions but with a not-too-well-defined central part. These peculiar behaviours are a consequence of the hydrogen-bonding inter­actions: the outermost SO3 parts of the pds anion are heavily connected to the complex cations via C—H⋯O hydrogen bonding, generating an [Ni(phen)3]pds network and providing for the stability of the terminal pds sites. Also, the water solvent mol­ecule is strongly bound to the structure (being a donor of two strong bonds and an acceptor of one) and is accordingly perfectly ordered. The peroxide O atoms in the pds middle region, instead, appear as much less restrained into their sites, which may explain their tendency to disorder. The cation–anion network leaves large embedded holes, amounting to about 28% of the total crystal volume, which are occupied by the DMF mol­ecules. The latter are weakly inter­acting with the rest of the structure, which renders them much more labile and, accordingly, prone to disorder.

In the title compound, [Hf(C9H6NO)]·C3H7NO·H2O, the hafnium(IV) atom is coordinated by four 8-quinolinolate (Ox) ligands, forming a slightly distorted square-anti­prismatic coordination polyhedron. The crystal packing is controlled by O—H⋯O and C—H⋯O hydrogen-bonding inter­actions and π–π inter­actions between quinoline ligands of neighbouring mol­ecules. The inter­planar distances vary between 3.150 (1) and 3.251 (2) Å, while centroid–centroid distances vary from 3.589 (1) to 4.1531 (1) Å.

In the title compound, 2C15H14N4O7·2C3H7NO·H2O, the hydrazone mol­ecules are roughly planar, with the two benzene rings twisted slightly relative to each other by dihedral angle of 6.04 (11) and 7.75 (11)° in the two mol­ecules. The water mol­ecule is linked to the Schiff base mol­ecule by an O—H⋯O hydrogen bond. Intra­molecular N—H⋯O hydrogen bonds occur. In the crystal, mol­ecules are linked by inter­molecular N—H⋯O and O—H⋯O hydrogen bonds.

In the title trinuclear NiII compound, [Ni3(C18H19N2O3)2(C5H5N)4]·C3H7NO·H2O, three NiII cations are bridged by two N′-(adamantan-1-ylcarbon­yl)-2-oxidobenzohydrazidate trianions. The central NiII cation has a distorted octa­hedral N4O2 coordination environment where a reverse torsion occurs between the two bridging ligands, whereas the two NiII cations on the sides each adopt an N2O2 square-planar coordination. Weak intra­molecular C—H⋯O and C—H⋯N inter­actions help to stabilize the mol­ecular structure. In the crystal, the lattice water mol­ecule links with the NiII complex and dimethyl­formamide solvent mol­ecule via O—H⋯O hydrogen bonding.

In the title compound, C13H16N10O2S·C5H9NO·H2O, the entire 1-methylpyrrolidin-2-one (NMP) mol­ecule is disordered over two sites with occupancies of 0.488 (5) and 0.512 (5). The six-membered triazine ring and the two five-membered pyrazole and thiadia­zole rings, together with the diazene (–N=N–) linkage are almost coplanar (r.m.s. deviation for the non-H atoms = 0.0256 Å) with methyl groups from the tert-butyl substituent on the pyrazole ring located above and below the plane. Three intra­molecular N—H⋯N hydrogen bonds contribute to the planarity of the system. The O atom of the NMP mol­ecule is hydrogen bonded to an O—H group of water. In turn, the water mol­ecule is hydrogen bonded to the mono-azo skeleton through inter­molecular N—H⋯O and O—H⋯N hydrogen bonds. At both ends of the long mol­ecular axis of the main mol­ecule there are inter­molecular N—H⋯N hydrogen bonds, arranged in a head-to-tail fashion, between the N—H group of the triazine ring of one mol­ecule and the N atom of the thia­diazole ring of a neighboring mol­ecule. These form a polymeric chain along [110] or [10]. The main mol­ecules are stacked alternately along the b axis, which effectively cancels their dipole moments. In addition, pairs of alternate molecules are dimerized via inter­molecular hydrogen bonds involving the solvent mol­ecules.

Purpose:

To report on the clinically important differences between nasal optic hypoplasia (NOH) and glaucoma with NOH-like temporal visual field defect (VFD).

Method:

Five NOH (four bilateral and one unilateral) patients, three unilateral NOH patients with glaucoma, and two glaucoma patients with NOH-like temporal VFD were clinically characterized. Superior segmental optic nerve hypoplasia was also associated with glaucoma in one eye of a bilateral NOH case and the NOH eye of a unilateral NOH patient. Ocular manifestations including refractive errors, size, and appearances of the optic discs, retinal nerve fiber thickness (NFLT) ascertained by optical coherence tomography (OCT), and VFD were examined.

Results:

Ophthalmic examinations revealing NOH showed high myopia at more than −5.0D, a small disc with nasal double-ring appearance, significantly decreased NFLT by OCT, and retinal nerve fiber layer defect in the corresponding nasal sector. Stationary temporal VFD varied from a slight depression of the peripheral isopters to wide sector defects. In contrast, two glaucoma patients with NOH-like temporal VFD showed several different clinical features, including mild myopia less than −5D, a normal size with glaucomatous disc cupping; a slight decrease in nasal NFLT and progression of temporal and other glaucomatous VFD.

Conclusion:

Careful evaluation of optic disc appearance and measurement of NFLT using OCT may help to distinguish between NOH and glaucoma with NOH-like temporal VFD.

The progression of kidney disease to renal failure correlates with infiltration of mononuclear immune cells into the tubulointerstitium. These infiltrates contain macrophages, DCs, and T cells, but the role of each cell type in disease progression is unclear. To investigate the underlying immune mechanisms, we generated transgenic mice that selectively expressed the model antigens ovalbumin and hen egg lysozyme in glomerular podocytes (NOH mice). Coinjection of ovalbumin-specific transgenic CD8+ CTLs and CD4+ Th cells into NOH mice resulted in periglomerular mononuclear infiltrates and inflammation of parietal epithelial cells, similar to lesions frequently observed in human chronic glomerulonephritis. Repetitive T cell injections aggravated infiltration and caused progression to structural and functional kidney damage after 4 weeks. Mechanistic analysis revealed that DCs in renal lymph nodes constitutively cross-presented ovalbumin and activated CTLs. These CTLs released further ovalbumin for CTL activation in the lymph nodes and for simultaneous presentation to Th cells by distinct DC subsets residing in the kidney tubulointerstitium. Crosstalk between tubulointerstitial DCs and Th cells resulted in intrarenal cytokine and chemokine production and in recruitment of more CTLs, monocyte-derived DCs, and macrophages. The importance of DCs was established by the fact that DC depletion rapidly resolved established kidney immunopathology. These findings demonstrate that glomerular antigen–specific CTLs and Th cells can jointly induce renal immunopathology and identify kidney DCs as a mechanistic link between glomerular injury and the progression of kidney disease.

Summary

Identifying the site of obstruction and the pattern of airway change during sleep are the key points essential to guide surgical treatment decision making for Obstructive Sleep Apnoea-Hypopnoea Syndrome in adults. In this investigation, 250 cases were retrospectively analyzed in order to compare the pharyngolaryngeal endoscopic findings detected in the awake state, with those obtained in drug-induced sedation, by means of the Sleep Endoscopy technique. All endoscopic findings have been classified according to the semi-quantitative NOH staging. The awake and sedation NOH resulted identical in 25% of the cases only, while the discrepancies involved the oropharyngeal and hypopharyngeal sites, respectively in about 33% and 50% of the patients. The laryngeal obstructive role detected during sedation in almost 33% of the cases was both unforeseen and relevant, with all the consequent implications in the treatment choices particularly for the surgical cases.

In the title dinuclear compound, [Zn2(C6H6N3O)2(C6H7N3O)2](NO3)2, the ZnII cation is N,N′-chelated by one pyridine-2-carboxamide oximate anion and one pyridine-2-carboxamide oxime mol­ecule, and is further bridged by an oxime O atom from the adjacent pyridine-2-carboxamide oximate anion, forming a distorted trigonal bipyramidal coordination. Two pyridine-2-carboxamide oximate anions bridge two ZnII cations to form the centrosymmetric dinuclear mol­ecule. Extensive O—H⋯O, N—H⋯O and O—H⋯N hydrogen bonds are present in the crystal structure.

In the title compound, {[Mn(C16H18N3O3)(C14H8O5)]·H2O}n, the unique MnII ion is coordinated by two O atoms from a chelating 1-ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro­quinoline-3-carboxyl­ate ligand and three O atoms from three 4,4′-oxydibenzoate ligands, forming a distorted square-pyramidal coordination environment. In the crystal structure, centrosymmetric dinuclear manganese units are linked via 4,4′-oxydibenzoate ligands into one-dimensional chains; these chains are, in turn, connected via inter­molecular N—H⋯O and O—H⋯O hydrogen bonds to form a two-dimensional supra­molecular network. The O atom of the solvent water mol­ecule is disordered over two sites with equal occupancies; the attached H atoms are common to both sites.

A new dinuclear iron nitrosyl complex [Fe2(C14H12N3S)2(NO)4] (1) (C14H12N3S = 2-mercapto-1-[2-(4-pyridyl)-ethyl]-benzimidazolyl) has been obtained by the reaction of Fe(NO)2(CO)2 with 2-mercapto-1-[2-(4-pyridyl)-ethyl]-benzimidazole in CH3OH under moderate condition. Complex 1 was characterized by IR, UV-vis, electrochemistry and single crystal X-ray diffraction. IR spectrum displays two strong characteristic NO stretching frequencies (νNO) in solution and in solid state. Cyclic voltammetry shows one irreversible, two quasi-reversible and two reversible one-electron reductions and irreversible oxidizations. This result is consistent with the fact that complex 1 is very unstable and ready to lose NO in the air. As showing in the single crystal X-ray diffraction, complex 1 forms a “chair-shape” structure by the connections of two iron centers and S-C-N frames of benzimidazole. The dihedral angle of benzimidazole ring and 2Fe-2S plane is 73.6°. The crystal data are the following: 1, monoclinic, space group P2(1)/c, a = 10.43940(10) Å, b = 16.0900(2) Å, c = 10.13240(10) Å, α = 90°, β = 111.0940(10) °, γ = 90°, V = 1587.89(3) Å3, Z = 4.

The reaction of di-2-pyridyl ketone with copper dichloride dihydrate and tartaric acid in water afforded the title compound, [Cu(C11H10N2O2)2]C4H4O6. The CuII atom lies on an inversion center N,O,N′-chelated by two di-2-pyridylmethane­diol ligands in a tetragonally distorted octa­hedral geometry. The tartrate anion is also located on an inversion center and has disordered hydroxyl groups, each with an occupancy factor of 0.5. The hydroxyl groups of the complex cation are hydrogen bonded to the carboxyl­ate groups of the anion, thus connecting the two building units.

The title hydrate, C26H21NO·H2O, exhibits significant twists of the benzene ring [dihedral angle = 87.24 (6)°] and chalcone residue [C—C—C—C torsion angle = −94.46 (17)°] out of the plane through the quinoline ring system. The conformation about the C=C bond [1.341 (2) Å] is E. The solvent water mol­ecule forms hydrogen bonds to carbonyl O and quinoline N atoms derived from two mol­ecules and through the application of a centre of inversion, a 16-membered {⋯HOH⋯OC3N}2 synthon is formed to stabilize the resulting tetra­meric (two organic mol­ecules plus two water mol­ecules) aggregate. These are connected into a two-dimensional array via two C—H⋯O contacts, also involving the water mol­ecule. The layers stack along the c axis, being linked by C—H⋯π inter­actions.

A series of rhenium(I) tricarbonyl complexes with the ligand 2,3,5,6-tetra(2-pyridyl)pyrazine (tppz) were synthesized and characterized crystallographically. Two different coordination modes were found when tppz functions as a monobidentate ligand. Rhenium(I) may be bound to tppz through pyrazine and pyridyl nitrogens completing a 5-membered coordination ring when the reaction was carried out in toluene. However, the same reaction in methanol produced a yellow complex in which rhenium(I) was bound to tppz through two adjacent pyridyl nitrogens with a 7-membered coordination ring. In the presence of an excess amount of [ReBr(CO)5], the dinuclear complex [{ReBr(CO)3}2(μ-tppz)] (3) was isolated, while the trinuclear complex [{ReCl(CO)3}3-(μ-tppz)] (4) was obtained in the case of [ReCl(CO)5]. Crystal data for 1, C27H16ClN6O3Re·MeOH: monoclinic, P21/n, a = 9.2217(7), b = 10.7628(8), c = 26.932(2) Å, β= 94.130(1)°, V = 2666.1(3) Å3, Z = 4. 2, C27H16BrN6O3Re: monoclinic, P21/n, a = 9.2931(6), b = 10.2387(7), c = 27.993(2) Å, β = 94.615(1)°, V = 2654.8(3) Å3, Z = 4. 1′, C27H16ClN6O3Re·2H2O: monoclinic, C2/c, a = 18.584(4), b = 21.693(5), c = 15.392(4) Å, β = 122.328(3)°, V = 5243(2) Å3, Z = 8. 3, C30H16Br2N6O6Re2: triclinic, P1̄, a = 7.4668(6), b = 11.4902(10), c = 19.3736(16) Å, α = 73.659(2), β = 85.183(2), γ = 77.097(1)°, V = 1554.3(2) Å3, Z = 2. 4, C33H16Cl3N6O9Re3·1/2C6H6: orthorhombic, Pbca, a = 18.828(1), b = 16.715(1), c = 25.366(2) Å, V = 7983.2(10) Å3, Z = 8.

The asymmetric unit of the title compound, [Co(HCO2)2(C14H12N2)(H2O)]·H2O, contains a mononuclear complex mol­ecule hydrogen bonded to a lattice water mol­ecule. The CoII cation is in a distorted octa­hedral coordination environment defined by the two N atoms of the 2,9-dimethyl-1,10-phenanthroline ligand and four O atoms. Two of these are from a chelating formate anion, one from a monodentate formate and the last from an aqua ligand. In the crystal, mol­ecules are connected by O—H⋯O hydrogen bonds, forming double chains along [100] with the 2,9-dimethyl-1,10-phenanthroline ligands pointing outwards from each chain. These chains are further linked into layers parallel to (011) by inter-chain π–π stacking inter­actions with centroid–centroid distances of 3.61 (1) Å.

The asymmetric unit of the title compound, [Ni(HCO2)2(C14H12N2)(H2O)]·H2O, contains a mononuclear complex mol­ecule hydrogen bonded to a lattice water mol­ecule. The NiII atom exhibits a distorted octa­hedral coordination geometry formed by the N atoms from a 2,9-dimethyl-1,10-phenanthroline ligand, two O atoms of a chelating formate anion, one aqua O atom and one O atom of a coordinating formate anion. The mol­ecules are assembled into chains extending along [100] through by O—H⋯O hydrogen bonds. The supra­molecular chains are further linked into layers parallel to (011) by weak π–π packing inter­actions [centroid–centroid separation = 3.768 (2) Å]. The resulting layers are stacked to meet the requirement of close-packing patterns.

We have shown that 4-Dibenzocyclooctynol (DIBO), which can easily be obtained by a streamlined synthetic approach, reacts exceptionally fast in the absence of a CuI catalyst with azido-containing compounds to give stable triazoles. Chemical modifications of DIBO, such as oxidation of the alcohol to a ketone, increased the rate of strain promoted azide-alkyne cycloadditions (SPAAC). Installment of a ketone or oxime in the cyclooctyne ring resulted in fluorescent active compounds whereas this property was absent in the corresponding cycloaddition adducts, thereby providing the first example of a metal-free alkyne-azide fluoro-switch click reaction. The alcohol or ketone functions of the cyclooctynes offer a chemical handle to install a variety of different tags, thereby facilitating biological studies. It was found that DIBO modified with biotin combined with metabolic labeling with an azido-containing monosaccharide can determine relative quantities of sialic acid of living cells that have defects in glycosylation (Lec CHO cells). A combined use of metabolic labeling/SPAAC and lectin staining of cells that have defects in the Conserved Oligomeric Golgi (COG) complex revealed that such defects have a greater impact on O-glycan sialylation than galactosylation, whereas sialylation and galactosylation of N-glycans was similarly impacted. These results highlight that the fidelity of Golgi trafficking is a critical parameter for the types of oligosaccharides that are being biosynthesized by a cell. Furthermore, by modulating the quantity of biosynthesized sugar nucleotide, cells may have a means to selectively alter specific glycan structures of glycoproteins.

The neurotoxicity of methyl n-butyl ketone is known to be enhanced by combination with methyl ethyl ketone. This study was conducted to clarify the potentiating effect of aliphatic monoketones on the neurotoxicity of methyl n-butyl ketone. Rats were subcutaneously injected in the back with 4 mmol/kg/day of methyl ethyl ketone, methyl n-propyl ketone, methyl n-amyl ketone, or methyl n-hexyl ketone mixed with an equimolar dose of methyl n-butyl ketone five days a week for 20 weeks. The maximum motor fibre conduction velocity and the distal latency were measured every two weeks in the tail nerves of the treated animals and controls. All the monoketones tested enhanced the neurotoxicity of methyl n-butyl ketone. Of the compounds tested, methyl n-hexyl ketone, which had the longest carbon chain, enhanced the neurotoxicity of methyl n-butyl ketone most strongly. These results suggest that the length of the carbon chain of the aliphatic monoketones combined with methyl n-butyl ketone was related to the enhancement of the neurotoxicity of the neurotoxic compound.