Mixture Of Trans Research Articles

Efforts to understand the degree of carboxylate substitution in cis-[Pt(S(O)Me2)(guanidine)Cl2]: Synthetic, Structural and DFT Studies

The reaction of N,N′,N″-tris(2-anisyl)guanidine, 1 with one equiv. of PhI(OAc)2 in acetonitrile under reflux condition for 6 h afforded a rigid 2-aminobenzimidazole type guanidine, 2 in 83% yield. The separate reactions of 2 with one equiv. of cis-[PtX2(S(O)Me2)2] (X = Cl and OC(O)CF3) in toluene under reflux condition for 8 h afforded mono adducts, cis-[PtX2(κ1N-2)(S(O)Me2)] (X = Cl (3) and OC(O)CF3 (4)) in 89% and 78% yields, respectively. The reaction of 3 with two equiv. of AgOC(O)CF3 in CH2Cl2 at RT for 24 h also afforded 4 in 82% yield. The reaction of 3 with one and two equiv. of AgOC(O)Me in CH2Cl2 at RT for 24 h afforded cis-[PtCl(OC(O)Me)(κ1N-2)(S(O)Me2)] (5) in 78% and 89% yields, respectively. Compounds 2–5 were characterised by elemental analyses, IR, NMR (1H, 13C{1H} and 19F) spectroscopies while 4 and 5 were also characterised by 195Pt{1H} NMR spectroscopy. Molecular structures of 2–5 were determined by single crystal X-ray diffraction (SCXRD). Complexes 3–5 exist as cis isomer in the solid state as revealed by SCXRD but as a mixture of cis (major) and trans (minor) isomers in solution as revealed by NMR spectroscopy. The reasons for the formation of bis(trifluoroacetato) complex, 4 versus mono-acetato complex, 5 irrespective of the molar ratio of the starting materials was rationalised based on the availability of greater amount of trifluoroacetate anion than acetate anion in solution from their respective Ag+ sources as deduced from DFT calculations.

Luminescence-activated Pt(IV) prodrug for in situ triggerable cancer therapy

Anticancer platinum prodrugs that can be controllably activated are highly desired for personalized precision medicine and patient compliance in cancer therapy. However, the clinical application of platinum(IV) prodrugs (Pt(IV)) is restricted by tissue penetration of external irradiation. Here, we report a novel Pt(IV) activation strategy based on endogenous luminescence of tumor microenvironment responsiveness, which completely circumvents the limitation of external irradiation. The designed Pt(IV)Lu, a mixture of trans, trans, trans-[Pt(N3)2(OH)2(py)2] and luminol (Lu), has controllable activation property: it remains inert in reductant environment and normal tissues, but under tumor microenvironment, Lu will be oxidized to produce blue luminescence, which rapidly reduce Pt(IV) to Pt(II) without the need of any external activator. Pt(IV)Lu shows excellent responsive antitumor ability both in vitro and in vivo. Compared to cisplatin, the median lethal dose in BALB/c mice increased by an order of magnitude. Our results suggest that Pt(IV)Lu exhibits highly controllable activation property, superior antitumor activity, and good biosafety, which may provide a novel strategy for the design of platinum prodrugs.

Serendipitous discovery of a regioselective synthesis of novel benzoyloxy substituted phenyl/benzyl-sulfanyl/selenylbisesters, 3-benzoyloxy-3-(phenylsulfanyl)-β-lactams and their antimicrobial evaluation

The regioselective benzoyloxylation process involves stirring a mixture of phenyl/benzyl-sulfanyl/selenylethanoate 1a-c with appropriate oxidant [benzoyl peroxide (BPO) 2a/ m-chloroperbenzoic acid (m-CPBA) 2b /bis(p-methoxybenzoyl peroxide) (BPM-BPO) 2c] under catalysis of hydrated copper acetate in toluene at 60 °C/RT. Regioselective C–H functionalization of esters 1a-c leads to benzoyloxy substituted phenyl/benzyl-sulfanyl/selenylbisesters 3a-g in good to excellent yields (80–95%). Variably substituted trans-3-phenylsulfanyl-β-lactams 4 employed for C3-H functionalization with BPO 2a generates diastereoisomeric mixture of trans- and cis-3-benzoyloxy-3-(phenylsulfanyl)-β-lactams 5 and 6 as major and minor isomers after efficient column chromatographic purification. The structural confirmation was done using IR, 1H NMR, 13C NMR, DEPT-90 NMR spectroscopic analysis and CHNS elemental analysis. In vitro antibacterial and antifungal evaluations on bisesters suggest benzylselenyl-bisester 3c as potent antimicrobial agent. Out of trans- and cis-3-benzoyloxy-β-lactams 5a and 6a, the trans isomer 5a was active against all microbial strains whereas the cis isomer 6a was completely inactive.

Exploring DNA-interaction and molecular structure of ruthenium/1,2-bis-(diphenylphosphino)ethane)-based complex

The mixture of cis and trans-[RuCl2(dppe)2] (dppe: 1,2-bis-(diphenylphosphino)ethane) was prepared and the interaction with CT-DNA was evaluated by several methods, including UV-vis DNA spectroscopic titration, viscosity, and electrochemical studies. Investigation suggests that [RuCl2(dppe)2] interacts moderately with CT-DNA. Interestingly, the cis- and trans-isomers interact differently with DNA, as proved by the square-wave voltammetry studies. Finally, the crystal structure of trans-[RuCl2(dppe)2]Cl was obtained from an electrochemical solution and studied in detail, which presents a distorted octahedral geometry and interatomic parameters different from those found in the trans-[RuCl2(dppe)2] complex. Crystal data for C52H48Cl4P4Ru: triclinic, space group P-1 (no. 2), a = 9.240(3) Å, b = 10.9290(18) Å, c = 11.993(3) Å, α = 78.707(11)°, β = 86.712(13)°, γ = 82.598(13)°, V = 1177.1(5) Å3, Z = 1, T = 293(2) K, μ(MoKα) = 0.732 mm-1, Dcalc = 1.467 g/cm3, 8434 reflections measured (6.934° ≤ 2Θ ≤ 51.986°), 4607 unique (Rint = 0.0973, Rsigma = 0.1171) which were used in all calculations. The final R1 was 0.0537 (I > 2σ(I)) and wR2 was 0.1347 (all data).

Trans-Trifluoromethyltetrafluorosulfanyl Chloride: Selective Synthesis and Reaction with Diazo Compounds.

trans-Trifluoromethyltetrafluorosulfanyl chloride (trans-CF3SF4Cl) is a unique reagent for the incorporation of the CF3SF4 group into organic compounds. However, CF3SF4Cl was prepared from hazardous reagents or formed as mixture of trans and cis isomers in low yield. Herein, a silver-promoted selective synthesis of trans-CF3SF4Cl under safe gas-reagent-free conditions is described. Furthermore, the synthetic application of trans-CF3SF4Cl is demonstrated through the new trifluoromethyltetrafluorosulfanylation of α-diazo carbonyl compounds.

318 (PB098) - Stereoisomeric effects of kusunokinin isomers on CSF1R selectivity

Background: Naturally extracted trans-(−)-kusunokinin from P. nigrum showed anticancer activities via binding and inhibition of CSF1R. However, the synthetic racemic mixtures of trans-(−)- and trans-(+)-kusunokinin (trans-(±)-kusunokinin) exhibited different effects on breast cancer cell lines. It was hypothesized that trans-(±)-kusunokinin bind to additional molecules, including AKR1B1. Previously, we found that trans-(−)-isomer had better relative binding energies (ΔGbind) than trans-(+)-isomer in every studied proteins.

Porous organic frameworks for preferable adsorption of trans-1,2-diols over cis-1,2-diols

• Porous organic frameworks for adsorption of vic- diols. • Preferable adsorption of trans-vic -diols over cis-vic -diols is possible. • Adsorption mechanism and selectivity depend on material structure. • MAS NMR to explore adsorption mechanisms. • Material application in a dynamic column setup. Novel separation processes are of utmost importance for a sustainable development of the chemical industry. In this work we show that polymer organic frameworks (POF) synthesized via condensation of melamine and a dialdehyde spacer exhibit superior selectivity towards adsorption of trans-vic -diols over cis - vic -diols. Mixtures of trans - and cis -1,2-cyclohexanediol as well as meso ‑ and ( R,R )-2,3-butanediol were applied for separation. Binding takes place due to cooperative hydrogen bonding of OH-groups of trans-diols to a nitrogen atom of the melamine ring and an NH-fragment of the aminal motif. The formation of the hydrogen bonds upon adsorption was supported by solid-state NMR experiments of samples after adsorption. Utilization of an aprotic solvent with low relative permittivity is of importance to achieve high adsorption capacities. The length of the dialdehyde spacer presents the major parameter governing the size of the micropores and thus the selectivity towards the trans -isomer. The best results were obtained for a POF prepared using 4,4′-biphenyldicarbaldehyde as spacer and bearing micropores with an average diameter of 0.67 nm. The average pore aperture is thus larger than the size of the tested diols, which are ca. 0.6 nm in length. Utilizing of isophtalaldehyde and phthalaldehyde as spacers gave rise to the sorption materials with average pore diameters of ca . 0.6 nm, comparable to the sizes of diol molecules. Adsorption of cis - and trans -diols onto the latter materials occurred owing to trapping in the pores, which resulted in strong van der Waals interactions leading to similar adsorption affinities of cis - and trans - isomers. The results of adsorption under batch and continuous conditions evidence the high potential of POF with 4,4′-biphenyldicarbaldehyde as spacer for adsorptive separation of trans - and cis -diols.

Nanoporous Vesicular Membranes of Amphiphilic Polymers Containing Trans / Cis Isomers

Nanoporous Vesicular Membranes of Amphiphilic Polymers Containing <i>Trans</i> / <i>Cis</i> Isomers

Ti-Catalyzed Reductive Dehydroxylative Vinylation of Tertiary Alcohols

Metal-catalyzed direct deoxygenative C(sp3)–C(sp2) coupling of alcohols is synthetically appealing, but it remains a particular challenge for the synthetic community. Herein, we demonstrate a radical dehydroxylative vinylation reaction of tertiary alcohols by Ti catalysis and, thus, establish a method for the construction of vinylated all-carbon quaternary centers. The reaction proceeds under mild conditions and tolerates various functionalities, including Ar–Bpin, Ar–SiMe3, alkyl chloride, phenol, nitrile, ester, furan, and thiophene. The reaction works with various vinyl halides, including fluorides, chlorides, bromides, and iodides. The use of a mixture of trans- and cis-haloalkenes gives the same trans products. The selectivity profiles were investigated among the vinyl and aryl electrophiles and among the different classes of alcohols.

Synthesis of limonene β-amino alcohol from (R)-(+)-α-methylbenzylamine and (+)-limonene 1,2-epoxide

Two new compounds of β-amino alcohol are obtained using (R) - (+) - α-methylbenzylamine as starting material which is converted into two amines. Each of these compounds reacted in excess with a 1: 1 mixture of cis and trans-limonene oxide in the presence of water as a catalyst. The products obtained show that β-amino alcohol derived from trans-limonene oxide is obtained and unreacted cis-limonene oxide from the reaction mixture as well as the amine is attained. Whereas the addition of the synthesized carbamate of the same primary amine over the 1: 1 mixture of cis and trans -limonene oxide in the presence of water results in the hydrolysis product and the recovery of unreacted trans-limonene oxide.

Monitoring the hepatic residues of cis- and trans-diastereoisomers of second generation anticoagulant rodenticides reveals a different bioaccumulation of diastereoisomers in the food chain of the Réunion harrier (Circus maillardi).

The Réunion harrier is an endangered raptor and endemic species to the Réunion Island. Second generation anticoagulant rodenticides (SGARs) are widely used pesticides on the island in order to control rodent populations. The latter are responsible for the transmission of leptospirosis to humans, the damage of sugarcane crops, and the decline of endemic endangered birds. SGARs are very persistent chiral pesticides and consequent secondary exposure or poisoning of the Réunion harrier has been observed (73% of prevalence in a group of 58 harriers). Commercial formulations of SGARs are a mixture of trans- and cis-diastereoisomers. Both diastereoisomers of all SGARs have been shown to inhibit coagulation function with the same potency. On the other hand, they have been shown to have a significant difference in terms of tissue-persistence. This difference has led to residue levels in rats with a significantly lower proportion of one of the isomers compared to the bait composition. In this study, residue levels of the diastereoisomers of all SGARs were evaluated in the livers of 58 harrier carcasses. The respective concentrations and proportions of cis- and trans- diastereoisomers of all SGARs are presented. cis-Brodifacoum and trans-bromadiolone had the highest concentrations (up to 438 and 573ng/g ww respectively), while trans-brodifacoum was less than 46ng/g and cis-bromadiolone was barely detected. cis-Difenacoum showed the highest prevalence and the highest concentration was 82ng/g ww, while trans-difenacoum was never detected. This study demonstrated that only cis-brodifacoum and trans-bromadiolone (and cis-difethialone, but with a low prevalence) had hepatic concentrations above a toxic threshold. The cis- and trans-diastereoisomers of SGARs had differential bioaccumulation in the food chain of the Réunion harrier compared to commercial baits. This suggests that a change of the proportions of SGARs diastereoisomers in baits could reduce the risk of secondary poisoning of predators, but maintain primary toxicity.

On the reaction between rhodium(III) bromide dihydrate and diphenylphosphine: Crystal and molecular structures of Trans-Bromotetrakis(diphenylphosphine)hydridorhodium(III) bromide, Trans-Dibromotetrakis(diphenylphosphine)rhodium(III) Trans-Tetrabromobis(diphenylphosphine)rhodate(III), and Mer-Tribromotris(diphenylphosphine)rhodium(III)

The aim of this work is to identify the products obtained from the chemical reaction between rhodium(III) bromide dihydrate and diphenylphosphine. If three to four equivalents of diphenylphosphine are used, a mixture of colorless trans-[Rh(H) (Br){PH(C6H5)2}4]Br (product A) and orange trans-[RhBr2{PH(C6H5)2}4]+trans-[RhBr4{PH(C6H5)2}2]- (product B) is formed, and these products are easily separated by filtration. Both A and B have been structurally characterized by single-crystal X-ray diffraction. If B is treated with excess diphenylphosphine, or if RhBr3 · 2H2O is treated with five or six equivalents of diphenylphosphine, then only A is formed. In CD3OD solution, H/D exchange occurs in A, leading to the penta-substituted isotopomer trans-[Rh(D) (Br){PD(C6H5)2}4]Br. Finally, a suspension of B in acetone-d6 at room temperature led to the formation of red crystals of mer-[RhBr3{PH(C6H5)2}3] (product C) after several days. C was also structurally characterized by single-crystal X-ray diffraction.

Structure of the intermediates in the industrial separation of perinone isomers

The industrial synthesis of perinone results in a mixed crystal containing an isomer mixture of trans- and cis-perinone. The isomers are separated by treatment with alcoholic KOH, which leads to a pale yellow precipitate and a yellow solution. The precipitate is subsequently hydrolyzed to produce pure trans-perinone (Pigment Orange 43). The yellow solution is treated with dilute acids to give cis-perinone (Pigment Red 194). The chemical structure and the stoichiometry of the intermediate pale yellow precipitate has never been determined, although this intermediate has been produced on a multi-ton scale for more than 80 years. The intermediate was assumed to be a “potassium hydroxide addition compound”. X-ray single-crystal analyses reveal that this assumption is wrong. The KOH/ethanol treatment actually causes a double ring-opening of the perinone. This results in the tetra-potassium salt of 4,8-bis(benzimidazolato)-naphthalene-1,5-dicarboxylate. Two phases were isolated: The α-phase, K4[C26H12N4O4]·3C2H5OH·6H2O, from the industrial synthesis and the β-phase, 1.5(K4[C26H12N4O4])·5C2H5OH·4H2O, from a recrystallization in KOH/ethanol. The molecular and crystal structures are confirmed by solid-state NMR spectroscopy through combination of 13C CPMAS and MAS experiments, which revealed that the solvent layers in the crystals show a highly dynamic solvent disorder in the solid state. The intermediate of cis-perinone, which is formed in the isomer separation step, has been isolated as well. Also this intermediate has a ring-opened molecular structure, as revealed by single-crystal X-ray diffraction.

Tris-(4,4'-di-tert-butyl-2,2'-bi-pyridine)(trans-4-tert-butyl-cyclo-hexa-nolato)-deca-μ-oxido-hepta-oxido-hepta-vanadium aceto-nitrile monosolvate including another unknown solvent mol-ecule.

The title hepta-nuclear alkoxido(oxido)vanadium(V) oxide cluster complex, [V7(C10H19O)O17(C18H24N2)3]·CH3CN, was obtained by the reaction of [V8O20(C18H24N2)4] with 4-tert-butyl-cyclo-hexa-nol (mixture of cis and trans) in a mixed CHCl3/CH3CN solvent. The complex has a V7O18N6 core with approximately C s symmetry, which is composed of two VO4 tetra-hedra, two VO6 octa-hedra and three VO4N2 octa-hedra. In the crystal, these complexes are linked together by weak inter-molecular C-H⋯O hydrogen bonds between the 4,4'-di-tert-butyl-2,2'-bi-pyridine ligand and the V7O18N6 core, forming a one-dimensional network along the c-axis direction. Besides the complex, the asymmetric unit contains one CH3CN solvent mol-ecule. The contribution of other disordered solvent mol-ecules to the scattering was removed using the SQUEEZE option in PLATON [Spek (2015 ▸). Acta Cryst. C71, 9-18]. The unknown solvent mol-ecules are not considered in the chemical formula and other crystal data.

Trapping of a Borirane Intermediate in the Reductive Coupling of an Arylborane to a Diborene.

The reductive coupling of a N-heterocyclic carbene (NHC)-stabilized aryldibromoborane yields a mixture of trans- and cis-diborenes in which the aryl groups are coplanar with the diborene core. Under dilute reduction conditions two diastereomers of a borirane-borane intermediate are isolated, which upon further reduction give rise to the aforementioned diborene mixture. DFT calculations suggest a mechanism proceeding via nucleophilic attack of a dicoordinate borylene intermediate on the aryl ring and subsequent intramolecular B-B bond formation.

Physical State of β‐Carotene at High Concentrations in a Solid Triglyceride Matrix

AbstractThe highly hydrophobic β‐carotene is often distributed or dissolved in triglycerides to enhance either nutritional or coloring effects. This study aims at elucidating the physical state of β‐carotene that at high concentrations are mixed into a solid high‐melting tri‐glyceride matrix by dissolution at high temperatures (165 °C) in the melted triglyceride. Extensive isomerization of β‐carotene is observed by HPLC after melting crystalline all‐trans β‐carotene and in the solid mixtures of β‐carotene and fully hydrogenated sunflower oil. Crystalline triglyceride is found in the mixed samples by XRPD analysis whereas no signs of crystalline lattice structures of β‐carotene are detected. DSC thermograms show only the melting and recrystallization events of triglycerides, which are affected by the presence of β‐carotene. Severe line broadening is observed in the 13C CP/MAS NMR spectra of the β‐carotene‐triglyceride mixtures when compared to crystalline β‐carotene, demonstrating the lack of long‐range order of the carotene. Altogether, the results demonstrate that β‐carotene is present as an amorphous mixture of trans‐ and cis‐isomers dispersed into a structure of crystalline triglyceride in the solid carotene‐triglyceride mixtures.Practical applications: The amorphous structure of trans‐ and cis‐isomers in solid formulations of β‐carotene‐triglyceride mixtures will strongly affect their functional properties related to nutrition and color as food ingredients.

Synthesis and Cytotoxic Evaluation of 3-Methylidenechroman-4-ones.

In the search for new anticancer agents, a library of variously substituted 3-methylidenechroman-4-ones was synthesized using Horner–Wadsworth–Emmons methodology. Acylation of diethyl methylphosphonate with selected ethyl salicylates furnished 3-diethoxyphosphorylchromen-4-ones which were next used as Michael acceptors in the reaction with various Grignard reagents. The adducts were obtained as the mixtures of trans and cis diastereoisomers along with a small amount of enol forms. Their relative configuration and preferred conformation were established by NMR analysis. The adducts turned up to be effective Horner–Wadsworth–Emmons reagents giving 2-substituted 3-methylidenechroman-4-ones, which were then tested for their possible cytotoxic activity against two leukemia cell lines, HL-60 and NALM-6, and against MCF-7 breast cancer cell line. All new compounds (14a–o) were highly cytotoxic for the leukemic cells and showed a moderate or weak effect on MCF-7 cells. Analog 14d exhibited the highest growth inhibitory activity and was more potent than carboplatin against HL-60 (IC50 = 1.46 ± 0.16 µM) and NALM-6 (IC50 = 0.50 ± 0.05 µM) cells. Further tests showed that 14d induced apoptosis in NALM-6 cells, which was mediated mostly through the extrinsic pathway.

Versatile coordination and C-H activation of a multi-donor phosphinoferrocene carboxamide ligand in Pd(ii) complexes.

A multi-donor phosphinoferrocene carboxamide, FcCONHCH2CH2PPh2 (1, Fc = ferrocenyl), was prepared, converted into the corresponding phosphine oxide 1O and phosphine selenide 1Se and, mainly, studied as a ligand in Pd(ii) complexes. In its native form, amide 1 preferentially coordinated soft Pd(ii) as a simple phosphine, giving rise to mixtures of cis and trans-[PdX2(1-κP)2] (2; X = Cl (a), Br (b), and I (c)), wherein the isomer ratios depended on the auxiliary halide ligand or, alternatively, to the complex [(LNC)PdCl(1-κP)] (6, LNC = 2-[(dimethylamino)methyl-κN]phenyl-κC1). This coordination mode was nevertheless easily changed when creating a vacant coordination site at the palladium. Thus, treatment of 2a with NH4[PF6] in the presence of free 1 produced [PdCl(1-κP)3][PF6] (3), while complete halogen removal with a Ag(i) salt led to cationic complexes cis-[Pd(1-κ2O,P)2]X2 (4, X = CF3SO3 (a), ClO4 (b), BF4 (c)) or [(LNC)Pd(1-κ2O,P)]X (7a and 7b), containing seven-membered O,P-chelate rings. In contrast, amide nitrogen deprotonation with KOt-Bu followed by spontaneous intramolecular halogen substitution resulted in the transformation of 6 into the chelate complex [(LNC)Pd{(1- H)-κ2N,P}] (8) featuring a five-membered N,P-chelate ring, and in the conversion of 2a and 2b into the product of C-H bond activation [Pd{Fe(η5-C5H3CONCH2CH2PPh2-κ3C,N,P)(η5-C5H5)}(1-κP)] (5), with doubly chelating deprotonated 1. Importantly, complexes 2-4-5 and 6-7-8 were mutually interconverted in triads (by protonation/deprotonation and by halide addition/abstraction), which highlights the flexible coordination and chemical stability of ligand 1. The crystal structures of 1O·½H2O, trans-2a·MeCN, trans-2b·3C2H4Cl2, trans-2c·2.5C2H4Cl2, 4a·CH2Cl2, 5·3CHCl3·Et2O, and 8 were determined by single-crystal X-ray diffraction analysis, and the representative compounds were studied by cyclic voltammetry.

HPLC Characterization of cis and trans Mixtures of Double-Decker Shaped Silsesquioxanes

HPLC was used as the quantitative analysis technique in determining the molar ratio of cis and trans isomers in the double-decker shaped silsesquioxanes (DDSQ). Different experiments were performed to analyze the effects in the retention times of the polarity of moieties bonded to the DDSQ, as well as other possible adsorption driving forces. As expected, the use of adsorption HPLC was successful in separating cis and trans DDSQ isomers with the resolution of elution better than 1.5. Interestingly, the molecular size of moiety attached to the DDSQ resulted in significant reduction of the retention time suggesting the sterics constraint plays a critical role in the separation of these cage-like structures along with the strength of hydrogen bonding. In partition HPLC using Si bonded with CN groups as a normal phase resulted in a partial separation for one of the selected systems, which indicates the extent of polarity plays a secondary role in the separation mechanism.

Synthesis, Receptor Affinity, and Antiallodynic Activity of Spirocyclic σ Receptor Ligands with Exocyclic Amino Moiety.

In order to detect novel σ receptor ligands, the rigid spiro[[2]benzopyran-1,1'-cyclohexan]-4'-one was connected with amino moieties derived from σ2 receptor preferring lead compounds resulting in mixtures of trans- and cis-configured amines 6, 18, and 27. In a four step synthesis the methyl acetals 6 were converted into fluoroethyl derivatives 13 and 30. The most promising σ2 receptor ligand is the methyl acetal 6a bearing a 2,4-dimethylbenzylamino moiety. The fluoroethyl derivatives 13c and 13d reveal high σ1 affinity but moderate selectivity over the σ2 subtype. In mice 13c and 13d showed antiallodynic activity that is stronger than that of the reference σ1 antagonist BD-1063 (34). Since the antiallodynic activity of 13c could only be partially reversed by the σ1 agonist PRE-084 (35), it is postulated that a second mechanism contributes to its overall antiallodynic effect. In contrast, the antiallodynic effect of its diastereomer 13d can be totally explained by a σ1 antagonism.