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The enantioselective 1,3-dipolar cycloaddition of nitrones and arylpropionaldehydes to generate highly functionalized scaffolds for application in drug discovery was herein investigated. The use of a second-generation MacMillan catalyst as hydrochloride salt consistently accelerated the reaction speed, allowing a decrease in the reaction time up to >100 times, still affording 4-isoxazolines with good to excellent enantiomeric ratios at room temperature. As a proof of concept, further functionalization of the isoxazoline core through Pd-catalyzed cross-coupling was performed, generating differently functionalized chemical architectures in high yield.

A dehydrogenative functionalization of styryl carbon-carbon double bonds with triflamide is described via dual visible-light photoredox/cobaloxime catalysis. A range of allylic triflamides (20 examples) were isolated in moderate to good yields (up to 88%) under stoichiometric acceptorless conditions. Dedicated labelling, as well as spectroscopic experiments, enabled to shed light on the concatenated photo- and chemo-catalytic cycles. (Figure presented.).

The reaction of select copper(II) monocarboxylates Cu(RCOO)2(H2O)x (R = C4H3O, C6H5, H; x = 2, 4) with pyrazole (Hpz), carried out in protic solvents, yields mono- or dinuclear species [Cu(RCOO)2(Hpz)n]m (n = 2, 4; m = 1, 2), always accompanied by tri- or hexanuclear derivatives based on the triangular [Cu3(μ3-OH)(μ-pz)3]2+ fragment. The molecular structures of all isolated compounds have been established through XRD determinations. In some cases, the mono-, or dinuclear species act as secondary building units, self-assembling into 1D or 3D coordination polymers. The hexanuclear benzoate cluster contains coordinated and crystallization MeOH molecules, whose removal generates a crystalline 1D coordination polymer that can be reconverted into the hexanuclear cluster by soaking in MeOH. The relatively high pKb values of carboxylate anions employed in the syntheses are responsible for the preferential formation of mono- or dinuclear species rather than tri- or hexanuclear ones.

A new [Au(I)] catalyzed intramolecular hydrocarboxylation of allenes is presented as a valuable synthetic route to oxazino-indolones. The use of 3,5-(CF3)2–C6H3–ImPyAuSbF6 as the optimal catalyst (5 mol%) was necessary to guarantee (i) wide tolerance of functional groups, (ii) mild reaction conditions (r.t., 16 h), and (iii) high yields (up to 90%). Preliminary attempts towards an enantioselective version (81 : 19 er) are also documented by means of a new family of chiral C1-symmetric ImPyAuCl complexes.

The synthesis of 1,3,4-trisubstituted pyrroles via visible-light mediated photoredox catalyzed condensation of arylazides and aldehydes has been reported herein. The methodology avoids the use of stoichiometric oxidants and provides the corresponding N-containing arenes in good yields (up to 78%) and mild conditions. Mechanistic rationale is provided via a dedicated and combined spectroscopic/experimental investigations.

Leishmaniases are neglected diseases that can be treated with a limited drug arsenal; the development of new molecules is therefore a priority. Recent evidence indicates that endoperoxides, including artemisinin and its derivatives, possess antileishmanial activity. Here, 1,2-dioxanes were synthesized with their corresponding tetrahydropyrans lacking the peroxide bridge, to ascertain if this group is a key pharmacophoric requirement for the antileishmanial bioactivity. Newly synthesized compounds were examined in vitro, and their mechanism of action was preliminarily investigated. Three endoperoxides and their corresponding tetrahydropyrans effectively inhibited the growth of Leishmania donovani promastigotes and amastigotes, and iron did not play a significant role in their activation. Further, reactive oxygen species were produced in both endoperoxide- and tetrahydropyran-treated promastigotes. In conclusion, the peroxide group proved not to be crucial for the antileishmanial bioactivity of endoperoxides, under the tested conditions. Our findings reveal the potential of both 1,2-dioxanes and tetrahydropyrans as lead compounds for novel therapies against Leishmania.

A carboxylative Ni-catalyzed tandem C-C σ-bond activation of cyclobutanones followed by CO

A carboxylative Ni-catalyzed tandem C-C σ-bond activation of cyclobutanones followed by CO2-electrophilic trapping is documented as a direct route to synthetically valuable 3-indanone-1-acetic acids. The protocol shows an adequate functional group tolerance and useful chemical outcomes (yield up to 76%) when AlCl3 is adopted as an additive. Manipulations of the targeted cyclic scaffolds and a mechanistic proposal based on experimental evidence complete the investigation.

New chiral BINOL-based phosphate counterions have been synthesized, fully characterized, and employed in the enantioselective gold-catalyzed dearomatization of -naphthols with allenamides. A range of densely functionalized C1-allylated naphthalenones were realized under mild conditions and high levels of chemo-, regio- and stereoselectivity (ee up to 95 %).

A novel asymmetric nickel-based procedure has been developed in which CO2 fixation is achieved as a second step of a truncated Heck coupling. For this, a new chiral ligand has been prepared and shown to achieve enantiomeric excesses up to 99 %. The overall process efficiently furnishes chiral 2,3-dihydrobenzofuran-3-ylacetic acids, an important class of bioactive products, from easy to prepare starting materials. A combined experimental and computational effort revealed the key steps of the catalytic cycle and suggested the unexpected participation of Ni(I) species in the coupling event.

The site-selective thio-allylation of electron-deficient 1,2-dienes is documented under scandium catalysis. The methodology enables the realization of alpha-beta unsaturated, beta-thio, gamma-allyl carboxylic acid derivatives via a one-pot Lewis acid promoted Michael addition/[3,3]-sigmatropic rearrangement sequence (20 examples) in high yields (up to 95%). Full rationalization of the reaction mechanism and stereochemical outcome is provided via DFT simulations

A series of oligomers containing alternate l-Ala and pGlu (pyroglutamic acid) both in the L and D form have been prepared and conformationally investigated by X-ray, NMR, UV/ECD, IR/VCD and molecular modelling. X-ray diffraction analysis was possible for the shortest oligomers LL-1 and LD-1. Molecular dynamics simulations of the oligomers demonstrated that the energy landscapes of the LL-series are broad. In contrast, the energy landscapes of the LD-series are characterized by well-defined minima corresponding to specific conformational structures. A single well-defined minimum exists in the energy landscape of the largest oligomer LD-8, corresponding to a precise conformation, characterized by i + 5 → i N-H⋯OC hydrogen bonds, typical of a π-helix. ECD and VCD spectra were measured to identify the chiroptical profiles of the oligomers. The most striking element in the ECD spectra of the LD-series is their exceptionally strong intensity, which confirms that these polypeptides attain a high degree of helical order. VCD spectra for the LD-series are well reproduced by frequency calculations when π-helix folds are employed as input structures, suggesting that a symmetrical VCD couplet around 1720 cm-1 can be taken as the VCD signature of π-helices.

The nickel catalyzed regio- and stereoselective condensation of boronic acids to allenamides is documented as a novel synthetic route to stereochemically defined tri-substituted enamides. The protocol has been implemented into a three-component variant intercepting the in situ formed allyl-Ni intermediate with a range of aldehydes. Additionally, evidence for the effective extension of this methodology to Me2Zn is documented. Full rationale on the mechanism as well as its stereochemical outcome is provided by a synergistic experimental/computational approach.

The site-selective allylative and allenylative dearomatization of indoles with alcohols was performed under carbocatalytic regime in the presence of graphene oxide (GO, 10 wt % loading) as the promoter. Metal-free conditions, absence of stoichiometric additive, environmentally friendly conditions (H2O/CH3CN, 55 degrees C, 6 h), broad substrate scope (33 examples, yield up to 92 %) and excellent site- and stereoselectivity characterize the present methodology. Moreover, a covalent activation model exerted by GO functionalities was corroborated by spectroscopic, experimental and computational evidences. Recovering and regeneration of the GO catalyst through simple acidic treatment was also documented.

A novel gold(i)-catalyzed protocol for the synthesis of 4H-1,3-dioxin-3-ones is presented. The protocol exploits a metal induced cascade sequence involving a [3,3]-sigmatropic rearrangement followed by regioselective O-annulation reactions. A wide range of oxygen-based heterocyclic scaffolds (21 examples) were achieved in excellent yield (up to 80%) and a detailed computational investigation as well as deuterium-labelling investigations enabled all the plausible reaction pathways to be mapped and the rationalization of the recorded regioselectivity.

A novel asymmetric nickel-based procedure has been developed in which CO

The TBD (1,3,5-triazabicyclodec-5-ene) assisted three-component carbonylation of pyridine-2-methana- mines is documented by means of CO2 as a benign CO surrogate. The redox-neutral methodology enables the re- alization of densely functionalized imidazo-pyridinones in high yields (up to 93%) and excellent chemoselectivity. Combined computational and experimental investigations revealed an unprecedented RCOCl/TBD concerted electro- philic activation of carbon dioxide.

The use of a new copper(I) coordination polymer (CP) as additive in transparent composite films of 190 nm of thickness for ultraviolet (UV) shielding is presented. The luminescent 1-D Cu(I) CP was easily synthesized through a self-assembly process between Cu(I) iodide and 2,6-bis(1H-benzotriazol-1-ylmethyl)pyridine (L). The CP, [Cu2(μ − I)2(μ − L)2]n, was structurally characterized by infrared, UV–visible diffuse reflectance and photoluminescence spectroscopy, elemental and thermogravimetric analyses, single-crystal and powder X-ray diffraction, and relativistic density functional theory calculations. The CP was dispersed and immobilized into a polymeric matrix in the presence of Sudan I, yielding a composite material that exhibits a reduction of 49% of the UV transmittance at 350 nm. Thus, the use of a new Cu(I) CP in polymeric composite films appears as a novel approach toward ultrathin and transparent UV shielding films, which have potential applications as protection layers of paints and coatings that tend to degrade when exposed to UV radiation.

The TBD (1,3,5-triazabicyclodec-5-ene) assisted three-component carbonylation of pyridine-2-methanamines is documented by means of CO

The stereoselective phosphine-catalyzed (( pMeOC

Nucleobases coordinated to Ruthenium centres have shown several promising properties for cancer treatments, demonstrating to have efficiency comparable to that of cis-Pt compounds, limiting toxic effects to intact cells and overcoming the drugs resistance after longer treatments. Thymine acetate (THAc) is proposed as a biomimetic model ligand to design potential Ruthenium-based antitumor drugs. Herein we report the reaction between Ru(H)2(CO)(PPh3)3, 1 and THAcH. The X-ray structure of the mono-,dihapto-thymine acetate species [(k1-O)(k2-O,O)Ru(THAc)2(CO)(PPh3)2] 2, unexpectedly exhibits cis-location for acetate ligands, likely ascribed to the prevalence of H-bonds and -stacking interactions. Conversely, DFT-calculations and NMR spectra suggest lower energy for the trans form where there are no contacts between the bulky phosphines. The DFT-calculated energies suggest the nature for NMR-intercepted plausible k1- or k2-intermediates. The carboxy-metal coordination is able to stabilize enol-tautomers through supramolecular H-interactions. The rotations of k1- and k2-acetate side arm of the THAc have also been exploited by correlating NMR signal patterns with the DFT energies. Figure 1: Torsional barrier of k1-(O) 3 and k2-(O,O) 4

The highly enantioselective synthesis of densely functionalized 2,3-indoline-cyclobutanes by means of chiral gold catalysis is presented. Intermolecular formal [2+2]-cycloaddition reactions between substituted indoles and allenamides enabled direct access to methylenecyclo- butane-fused indolines, featuring two consecutive quaternary stereo- genic centers with excellent stereochemical control (dr 4 20:1, ee up to 99%).

The azo coupling reaction between 4-nitrobenzenediazonium tetrafluoroborate and a series of benzene derivatives bearing as electron donating substituents at least one hydroxy or methoxy group has been carried out. Depending on the nucleophile and its relative ratio with the diazonium salt it was possible to obtain mono-, di-, and, only in the case of phloroglucinol, evidence of trisubstitution products. The reaction between 3,5-diaminoanisole- or 3,5-diaminophenol- derivatives and two equivalents of diazonium salt gave, in the first case, the product derived from a mono attack, and a diadduct in the second case; their X-ray diffraction analysis showed an highly symmetric structure for the latter. The different behavior of hydroxy- with respect to the methoxy-substituted compounds was particularly evident for phloroglucinol and 1,3,5-trimethoxybenzene and it may be rationalized on the basis of the different electronic effect of the substituents. The propensity to undergo H/D exchange reaction on the aromatic ring was investigated on a series of substrates and the comparison of the results obtained provided new insights on this kind of phenomenon and permitted a better explanation of the findings reported here, by introducing a new particular interaction which competes with the -complex formation between proton and phloroglucinol

The site selective synthesis of functionalized indoles is presented under environmentally convenient tetrabutylammonium fluoride catalysis. The metal-free approach exploits the combined efficiency of Bu4N+ and F− ions in performing a cascade sequence involving intramolecular hydroamination of the C–C triple bond, cleavage of silyl-protecting groups and site-selective sigmatropic aza-Cope-type [3,3]-rearrangement. A range of C(3)-allenyl-(1H)-indoles (2) is obtained in an efficient manner (yield up to 93%) providing a valuable synthetic alternative to noble metal-based protocols.

The stereoselective synthesis of (E)-trisubstituted tertiary enamides is documented via site-selective Ni-catalyzed β-arylation of allenamides with boronic acids in high yields (up to 89%). The nucleophilic character of the “organo-Ni” intermediates is further exploited to implement a one-pot tricomponent procedure involving the final allylation of aldehydes (yields up to 93%). Mechanistic insights and efficiency on a gram scale process were also documented.

New organoruthenium [(η 6 -arene)Ru II (L)Cl]Cl ( 1 : arene = p -cymene, L = L 1 ; 2 : arene = p -cymene, L = L 2 ; 3 : arene = benzene, L = L 1 ; 4 : arene = benzene; L = L 2 ; L 1 = bis(3,5-dimethylpyrazolyl)parabenzoic acid, L 2 = bis(3,5-dimethylpyrazolyl)metabenzoic acid) have been synthesized and characterized by analytical and spectroscopic methods. The molecular structure of [(η 6 - p -cymene)RuCl(L 1 )]Cl ( 1 ) was determined by single crystal X-ray diffraction studies. Preliminary in vitro binding studies of 1 – 4 with CT DNA were carried out by employing various biophysical techniques which revealed their avid DNA binding via non-covalent binding mode viz; partial intercalation of the η 6 -arene group as well as electrostatic surface interaction through one oxygen atom of the phosphate backbone of the DNA helix; however, complexes 1 and 3 display higher binding propensity in comparison to 2 and 4 , as quantified by K b . The interaction was further analysed by HPLC technique. The results of the cleavage experiments of pBR322 DNA with 1 and 3 displayed significantly good cleavage at 20–40 μM, following the oxidative pathway. These findings have revealed that the hydrophobic arene, and the chloride leaving group have important roles in the novel mechanism of recognition of DNA by (η 6 -arene)ruthenium(II) complexes, and will aid the design of more effective anticancer complexes, as well as new site-specific DNA reagents. Furthermore, the anticancer activity of the complexes 1 and 3 on 15 cell lines of different histological origin has been studied. It has been observed that 1 exhibits higher cytotoxicity than 3 , and the cells undergo apoptotic cell death.

A careful interplay between the π electrophilicity of a cationic Au I center and the basicity of the corresponding counterion allowed for the chemo- and regioselective inter- as well as intramolecular de-aromatization of 2,3-disubstituted indoles with allenamides. The silver-free bifunctional Lewis acid/Brønsted base complex [{2,4-(tBu)2C 6H3O}3PAuTFA] assisted the formation of a range of densely functionalized indolenines under mild conditions.

The synthesis, the structural characterization and the luminescence spectroscopy of new Ln(III) nitrate complexes (Ln = La, Eu, Gd, Tb and Lu) with the quinoline-based N, N’-bis(2-quinolylmethylidene)- 1,2-(R,R+S,S)-cyclohexanediamine, L1 and N, N’-bis(2-quinolylmethyl)- 1,2-(R,R+S,S)-cyclohexanediamine, L2 are presented. All the L1Ln(NO3)3 complexes and L2Ln(NO3)3 with Ln= La, Eu and Tb are isostructural. Metal ions such as La(III), Gd(III) and Lu(III) are able to promote intra-ligand (IL) fluorescence from L1 and L2. Gd(III) and Lu(III) in addition, are also able to stimulate IL phosphorescence at room temperature from the L2 ligand, by means of “paramagnetic effect” and/or “heavy-atom effect”. Both ligands are able to sensitize the typical f-f Eu(III) luminescence and only L2 the one of Tb(III) (green emission). The Eu(III) emission features for both complexes [L1Eu(NO3)3 and L2Eu(NO3)3] are in agreement with their structural properties. All the complexes under investigation reveal promising application in the field of luminescent devices and biomedicine. In particular, excitation at 360 nm, in the case of L1-based complexes, enable the use of glass optics and minimize interfering excitation by chromophores in biological media.

The reactions of 4,4'-bipyridine with selected trinuclear triangular copper(II) complexes, [Cu-3(mu(3)-OH)(mu-pz)(3)(RCOO)(2)L-x], [pz = pyrazolate anion, R = CH3(CH2)(n) (2

The site-selective dearomatization of naphthols is realized in a straightforward manner through a gold(I)-catalyzed [3,3]-sigmatropic rearrangement/allene functionalization cascade sequence. The method employs readily available naphthylpropargyl ethers as starting materials. A range of densely functionalized dihydrofurylnaphthalen-2(1H)-ones are obtained in high yields (up to 98 %) and extremely mild reaction conditions (reagent grade solvent, air, 10 minute reaction time). A complete theoretical elucidation of the reaction machinery is also proposed, providing a rationale for important issues such as regio- and chemoselectivity.

The reaction between bis(2-benzothiazolyl)ketone and vinyl Grignard reagents bearing different substituents on the vinyl moiety gave the product derived from attack on the carbonylic carbon- and/or oxygen-atom. The regioselectivity of the attack depends on the kind of substituents bound to the vinylic carbon atoms and on their relative position. The reaction between vinylmagnesium bromide and 2-methyl-1-propenylmagnesium bromide was carried out under different experimental conditions and in the presence of radical scavengers. The results indicate a plausible mechanistic pathway involving radical intermediates in the case of O-alkylation, but a polar ones in the case of classic C-alkylation. This agrees with our previous reports indicating a key role played by the delocalization ability of the substituents bound to the carbonyl group in driving the regioselectivity of the vinylmagnesium bromide attack towards O-alkylation. Further support of this was obtained by diffractometric analysis of four distinct bis(heteroaryl)ketones.

A new chiral complex {[EuL(tta)2(H2O)]CF3SO3; L = N, N'-bis(2-pyridylmethylidene)-1,2-( R, R + S, S)-cyclohexanediamine; tta = 2-thenoyltrifluoroacetyl-acetonate} has been synthesized and characterized from a structural and spectroscopic point of view. The molecular structure in the solid state shows the presence of one chiral L, two tta, and one water molecules bound to the metal center. L and tta molecules can efficiently harvest and transfer to Eu(III) the UV light absorbed in the 250-400 nm range. The forced electric-dipole 5D0 → 7F2 emission band dominates the Eu(III) emission spectra recorded in the solid state and in solution of acetonitrile or methanol and the calculated intrinsic quantum yield of the metal ion is around 40-50%. The light emitted by the enantiopure complex shows a sizable degree of polarization with a maximum value of the emission dissymmetry factor ( glum) equal to 0.2 in methanol solution. If compared with the complex in the solid state or in acetonitrile solution, then the first coordination sphere of Eu(III) when the complex is dissolved in methanol is characterized by the presence of one CH3OH molecule instead of water. This fact is related to different Eu(III) CPL signatures in the two solvents.

The selective conversion of variously substituted epoxides into the corresponding cyclic carbonates under mild reaction conditions was achieved with mononuclear Fe(III) complexes bearing bis-thioether-diphenolate [OSSO]-type ligands, in combination with tetrabutylammonium bromide (TBAB). For example, propylene carbonate was obtained in 1 h at 35 °C (turnover frequency, TOF = 290 h-1), from propylene oxide and 1 bar of CO2 pressure, using 0.1 mol % of the Fe(III) complex and 0.5 mol % of TBAB. Product divergence is observed only for cyclohexene oxide toward the exclusive formation of the aliphatic polycarbonate (TOF = 165 h-1 at 80 °C and 1 bar of CO2 pressure, using 0.1 mol % of the Fe(III) complex and 0.1 mol % of tetrabutylammonium chloride). Kinetic investigations indicated reaction orders of two and one, with respect to the Fe(III) complex, for the production of propylene carbonate and the poly(cyclohexene carbonate), respectively. The enthalpy and entropy of activation were determined using the Eyring equation [for propylene carbonate: δH‡ = 8.4 ± 0.7 kcal/mol and δS‡ = -33 ± 3 cal/(mol·K); for poly(cyclohexene carbonate): δH‡ = 11.9 ± 0.3 kal/mol and δS‡ = -36 ± 2.2 cal/(mol·K)]. Supported by density functional theory based investigations, we propose a mechanistic scenario in which the rate-limiting step is the bimetallic ring opening of the epoxide, in the case of propylene carbonate, and the monometallic insertion of the epoxide in the growing polymer chain, in the case of poly(cyclohexene carbonate).

[object Object]Different synthetic procedures lead to different coordination polymers (CPs) based either on the trinuclear triangular [Cu3(? 3-OH)(?-pz)3]2+ or on the mononuclear [Cu(Hpz)3]2+ (Hpz=pyrazole) secondary building units (SBUs), bridged by the flexible glutarate (Glu) dianion. The mononuclear complex [Cu(HGlu)2(Hpz)4] was also obtained as byproduct. One of the CPs based on the trinuclear SBU displays a relevant porosity due to three intersecting channels, accounting for about 40% of the solvent accessible void space.

Ferrocene with its aromaticity and facile redox properties is an attractive moiety to be incorporated into functional moieties. Medicinal applications of ferrocene are well known and ferrocene itself shows cytotoxic and antianemic properties. In this article, we will describe the synthesis and the structure analysis of two pseudopeptides containing a ferrocene moiety as N-terminal group. After purification, Fc-L-Phe-D-Oxd-OBn [L-Phe=L-phenylalanine; D-Oxd=(4R,5S)-4-Methyl-5-carboxy-oxazolidin-2-one] appears as bright brown solid that spontaneously forms brown needles. The X-ray diffraction of the crystals shows the presence of strong p interactions between the ferrocenyl moiety and the phenyl rings, while no NAH center dot center dot center dot O=C hydrogen bonds are formed. This result is confirmed by FT-IR and H-1 NMR analysis. In contrast, both FT-IR and H-1 NMR analysis suggest that Fc-(L-Phe-D-Oxd)(2)-OBn forms a turn conformation stabilized by intramolecular NAH center dot center dot center dot O=C hydrogen bonds in solution. Chiroptical spectroscopies (ECD and VCD) substantially confirmed the absence of a well-defined folded structure. The presence of the Fc moiety is responsible for specific ECD signals, one of which displayed pronounced temperature dependence and is directly related with the helicity assumed by the Fc core. Solid-state ECD spectra were recorded and rationalized on the basis of the X-ray geometry and quantum-mechanical calculations.

By reacting 4,4′-bipyridine (bpy) with selected trinuclear triangular CuII complexes, [Cu3(μ3-OH)(μ-pz)3(RCOO)2(LL′)] [pz = pyrazolate anion; R = CH3, CH3CH2, CH2═CH, CH2═C(CH3); L, L′ = Hpz, H2O, MeOH] in MeOH, the substitution of monotopic ligands by ditopic bpy was observed. Depending on the stoichiometric reaction ratios, different compounds were isolated and structurally characterized. One- and two-dimensional coordination polymers (CPs), as well as two hexanuclear CuII clusters were identified. One of the hexanuclear clusters self-assembles into a supramolecular three-dimensional structure, and its crystal packing shows the presence of two intersecting channels, one of which is almost completely occupied by guest bpy, while in the second one guest water molecules are present. This compound also shows a reversible, thermally induced, single-crystal-to-single-crystal transition.

The syntheses of new Pt-II complexes with 4-acyl-5-pyrazolones [HQ(Ph) = 1-phenyl-3-methyl-4-benzoylpyrazol-5-one, a; HQ(py,CF3) = 1-(2-pyridyl)-3-methyl-trifluoroacetylpyrazol-5-one, b] are reported: trans-[PtCl2(DMSO)(HQ(Ph))] (1a), cis-[PtCl2(DMSO)(HQ(Ph))] (2a), [PtCl(DMSO)(Q(py,CF3))] (1b), and [PtCl2(KQ(py,CF3))] (2b). All complexes were characterized by multinuclear (H-1, C-13, F-19, and Pt-195), multidimensional NMR spectroscopy and single-crystal X-ray diffraction analyses. The isomer trans-[PtCl2(DMSO)(HQ(Ph))] (1a) crystallizes in two polymorphic forms, which correspond to two different conformers. In the trans-syn conformer (1a(M)) (monoclinic, space group P2(1)/c), the H atom of the enol group [O(1)H(1)] establishes an intramolecular hydrogen bond with the ketone oxygen (O2), whereas in the trans-anti conformer (1a(O)) (orthorhombic, space group Pca2(1)), the same groups are involved in an analogous intermolecular H bond. Interestingly, the cis isomer (2a) showed in solution and at room temperature slow rotation around both the Pt-N1 and the Pt-S bonds, which restrained both the acylpyrazolone and DMSO ligand motion. Moreover, the water solubility of the complexes trans- and cis-[PtCl2(DMSO)(HQ(Ph))] (1a and 2a) and [PtCl2(KQ(py,CF3))] (2b) allowed to perform in vitro biological assays on platinum-sensitive human endometrium (HeLa) and platinum-resistant human breast (MCF-7) cancer cell lines. It was also possible to compare their cytotoxicity to cisplatin. Interestingly, trans isomer 1a showed higher cytotoxicity on HeLa cells compared to the cis isomer 2a.

The highly diastereoselective anti-dioxylation of (1R,2R)-1,2-bis[(1S)-phenylethylamino]cyclohexene was accomplished through epoxidation of the double bond with m-chloroperbenzoic acid (mCPBA) in the presence of a sulfonic or trihaloacetic acid and ring opening of the epoxide in situ in the presence of sulfonate or carboxylate anions. The two procedures, after basic quenching and reductive removal of the N-substituents, provide stereoselective access to 2-exo-5-endo-5-amino-7-azabicyclo[2.2.1]heptan-2-ol and 4,5-diaminocyclohexane-1,2-diol, respectively. The different outcomes are explained by differing chair conformations of the protonated diamine-epoxide intermediates, which undergo ring opening through a preferred anti-diaxial mechanism.