Maximiliano Martínez-Cifuentes

Electrochemical characterization of hydroquinone derivatives with different substituents in acetonitrile

The effect of carbonyl groups in the ortho position with respect to a hydroxyl group on the electrochemical oxidation of hydroquinones in acetonitrile is studied. The electrochemical response of hydroquinone on a glassy carbon electrode in 0.1 M tetrabutylammonium perchlorate was investigated in detail by voltammetry and coulometry. From these experiments, the oxidation potential was shifted to more positive values with respect to hydroquinone due to the presence of electron withdrawing groups bonded to the aromatic ring. For all compounds a diffusional behavior was observed, and the diffusion coefficient (D) of substituted hydroquinones was calculated showing higher values than found for unsubstituted hydroquinone. Theoretical calculations were carried out to gain insights into the intramolecular hydrogen bond present in these molecules affecting their electrochemical behavior. Relevant theoretical data are optimized geometrical parameters, HOMO energy, condensed radical Fukui functions (f°), natural charges, Wiberg bond orders (WBO), stabilization energies caused by electron transfer, and hyperconjugation stabilization energies from the NBO analysis. In most cases, the calculations show good agreement with experimental 1H-NMR data and support the electrochemical results.

Intramolecular hydrogen bond in biologically active o-carbonyl hydroquinones.

Intramolecular hydrogen bonds (IHBs) play a central role in the molecular structure, chemical reactivity and interactions of biologically active molecules. Here, we study the IHBs of seven related o-carbonyl hydroquinones and one structurally-related aromatic lactone, some of which have shown anticancer and antioxidant activity. Experimental NMR data were correlated with theoretical calculations at the DFT and ab initio levels. Natural bond orbital (NBO) and molecular electrostatic potential (MEP) calculations were used to study the electronic characteristics of these IHB. As expected, our results show that NBO calculations are better than MEP to describe the strength of the IHBs. NBO energies (∆Eij(2)) show that the main contributions to energy stabilization correspond to LP→σ* interactions for IHBs, O1…O2-H2 and the delocalization LP→π* for O2-C2 = Cα(β). For the O1…O2-H2 interaction, the values of ∆Eij(2) can be attributed to the difference in the overlap ability between orbitals i and j (Fij), instead of the energy difference between them. The large energy for the LP O2→π* C2 = Cα(β) interaction in the compounds 9-Hydroxy-5-oxo-4,8, 8-trimethyl-l,9(8H)-anthracenecarbolactone (VIII) and 9,10-dihydroxy-4,4-dimethylanthracen-1(4H)-one (VII) (55.49 and 60.70 kcal/mol, respectively) when compared with the remaining molecules (all less than 50 kcal/mol), suggests that the IHBs in VIII and VII are strongly resonance assisted.

An ortho-carbonyl substituted hydroquinone derivative is an anticancer agent that acts by inhibiting mitochondrial bioenergetics and by inducing G2/M-phase arrest in mammary adenocarcinoma TA3

Tumor cells present a known metabolic reprogramming, which makes them more susceptible for a selective cellular death by modifying its mitochondrial bioenergetics. Anticancer action of the antioxidant 9,10-dihydroxy-4,4-dimethyl-5,8-dihydroanthracen-1(4H)-one (HQ) on mouse mammary adenocarcinoma TA3, and its multiresistant variant TA3-MTXR, were evaluated. HQ decreased the viability of both tumor cells, affecting slightly mammary epithelial cells. This hydroquinone blocked the electron flow through the NADH dehydrogenase (Complex I), leading to ADP-stimulated oxygen consumption inhibition, transmembrane potential dissipation and cellular ATP level decrease, without increasing ROS production. Duroquinol, an electron donor at CoQ level, reversed the decrease of cell viability induced by HQ. Additionally, HQ selectively induced G₂/M-phase arrest. Taken together, our results suggest that the bioenergetic dysfunction provoked by HQ is implicated in its anticancer action.

Thermodynamics and 2H NMR study on the insertion of small quinones into a discotic nematic lyotropic liquid crystal.

A detailed description of the distribution, interaction, and dynamics of molecules with biological activity dissolved in a hydrophobic bilayer, a simple model of a biological membrane, provides valuable information for a better understanding of drug functioning, which can be very useful in drug design. Here we present an (2)H NMR and molecular dynamics study on the insertion, distribution, interactions, and thermodynamics of two biologically active molecules, 9,10-dihydroxy-4,4-dimethyl-1,4,5,8-tetrahydroanthracen-1-one (HQ), with anticancer activity, and 4,4-dimethyl-1,4,5,8,9,10-hexahydroanthracen-1,9,10-trione (Q) a fungicide, dissolved in a nematic discotic lyotropic liquid crystal (ndllc) composed of sodium dodecylsulphate (SDS), decanol (DecOH) and Na2 SO4 in water. (2)H NMR quadrupole splittings (ΔνQ ) and longitudinal relaxation times (T1) from HQ-d6, Q-d4, DecOH-α-d2, partially deuterated water, and SDS-d25 were measured and several molecular dynamics trajectories were also calculated. In particular, ΔG, ΔH, and ΔS profiles for the process of both molecules crossing the bilayer were estimated. It was evidenced that the insertion of both molecules into the aggregate is a spontaneous process, and the molecules are mainly distributed in the internal side of the interface. Addition of HQ or Q decreased the mobility of all aggregate components, but this effect was more pronounced for HQ. The rotational correlation time of Q allowed an estimate of 5.3 cP for the microviscosity inside the ndllc aggregate, in the order of previously measured values in similar environments. Both guest molecules display similar free-energy profiles for the process of crossing the bilayer, with a calculated barrier height of 25 and 36 kJ mol(-1) for HQ and Q, respectively.

Impact of an integrated process of hot pressurised liquid extraction-macroporous resin purification over the polyphenols, hydroxymethylfurfural and reducing sugars content of Vitis vinifera ‘Carménère’ pomace extracts

1 Programa Institucional de Fomento a la Investigaci on, Desarrollo e Innovaci on, Universidad Tecnol ogica Metropolitana, Ignacio Valdivieso 2409, P.O. Box 9845, Santiago 8940577, Chile 2 Chemical and Bioprocess Engineering Department, School of Engineering, Pontificia Universidad Cat olica de Chile, Vicu~ na Mackenna 4860, P.O. Box 306, Santiago 7820436, Chile 3 Escuela de Ingenier ıa Agroindustrial, Universidad Nacional de Moquegua, Prolongaci on calle Ancash, Moquegua 18001, Per u 4 Departamento de Qu ımica, Universidad Tecnol ogica Metropolitana, Las Palmeras 3360, P.O. Box 7800003, Santiago, Chile

8,8-Diethyl-1,4,5,8-tetra-hydro-naphthalene-1,4,5-trione

The title molecule, C14H14O3, contains two fused six-membered carbon rings with keto groups at positions 1, 4 and 5 and a gem-diethyl group at position 8. The molecule is close to planar (maximum deviation = 0.044 Å), with one ethyl group at each side of the molecular plane, with exception of the keto group at position 1 which is slightly deviated from the plane and disordered over two positions one on each side of it (occupancies 0.80/0.20). The packing of the molecule shows weak bonded chains along a through C—H⋯O contacts and two intramolecular C—H⋯O interactions are also present.

A study about regioisomeric hydroquinones with multiple intramolecular hydrogen bonding

A theoretical exploration about hydrogen bonding in a series of synthetic regioisomeric antitumor tricyclic hydroquinones is presented. The stabilization energy for the intramolecular hydrogen bond (IHB) formation in four structurally different situations were evaluated: (a) IHB between the proton of a phenolic hydroxyl group and an ortho-carbonyl group (forming a six-membered ring); (b) between the oxygen atom of a phenolic hydroxyl group and the proton of an hydroxyalkyl group (seven membered ring); (c) between the proton of a phenolic hydroxyl group with the oxygen atom of the hydroxyl group of a hydroxyalkyl moiety (seven-membered ring); and (d) between the proton of a phenolic hydroxyl group and an oxygen atom directly bonded to the aromatic ring in ortho position (five-membered ring). A conformational analysis for the rotation around the hydroxyalkyl substituent is also performed. It is observed that there is a correspondence between the conformational energies and the IHB. The strongest intramolecular hydrogen bonds are those involving a phenolic proton and a carbonyl oxygen atom, forming a six-membered ring, and the weakest are those involving a phenolic proton with the oxygen atom of the chromenone, forming five-membered rings. Additionally, the synthesis and structural assignment of two pairs of regioisomeric hydroquinones, by 2D-NMR experiments, are reported. These results can be useful in the design of biologically-active molecules.

Protonation Sites, Tandem Mass Spectrometry and Computational Calculations of o-Carbonyl Carbazolequinone Derivatives.

A series of a new type of tetracyclic carbazolequinones incorporating a carbonyl group at the ortho position relative to the quinone moiety was synthesized and analyzed by tandem electrospray ionization mass spectrometry (ESI/MS-MS), using Collision-Induced Dissociation (CID) to dissociate the protonated species. Theoretical parameters such as molecular electrostatic potential (MEP), local Fukui functions and local Parr function for electrophilic attack as well as proton affinity (PA) and gas phase basicity (GB), were used to explain the preferred protonation sites. Transition states of some main fragmentation routes were obtained and the energies calculated at density functional theory (DFT) B3LYP level were compared with the obtained by ab initio quadratic configuration interaction with single and double excitation (QCISD). The results are in accordance with the observed distribution of ions. The nature of the substituents in the aromatic ring has a notable impact on the fragmentation routes of the molecules.

On-Water Reactivity and Regioselectivity of Quinones in C–N Coupling with Amines: Experimental and Theoretical Study

A study about the oxidative coupling of some representative carbo- and heterocyclic non-symmetrical quinones with aryl- and alkylamines, was carried out comparing dichloromethane and water as reaction mediums. We found that the on-water reactions gave better or, at worst, the same results as a conventional organic medium like dichloromethane. Descriptors derived from conceptual density functional theory and approaches of electrostatic nature, such as the molecular electrostatic potential, were used to explain the observed chemical reactivity and regioselectivity. Further, the on-water conditions were used to obtain 24 new aminoquinones with potential biological activity.

9,10-Dihydr­oxy-4,4-dimethyl-5,8-dihydro­anthracen-1(4H)-one

In the title molecule, C16H16O3, the ring system is planar and an intramolecular hydrogen bond is present. The molecular packing is dominated by an intermolecular hydrogen bond and by π-stacking interactions [interplanar separation 3.8012 Å].