An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
The redox propexties of a series of l-azaanthracene-9,10-diones, l$-diazaanthracene-9,10-diones, ... more The redox propexties of a series of l-azaanthracene-9,10-diones, l$-diazaanthracene-9,10-diones, 1 $-diazaanthracene-(lH)2,9,1O-triones and 1,8-diazaanthracene-(lH, 8H)2,7,9,lO-terraones have been studied. The results obtained show that the 2pyridone moiety is a stronger electron acceptor than the pyridine ring, in agreement with reactivity data. 1-Hydroxy-lazaanthracene-2,9,10-triones, synthesized from l-azaanthracene-9,1O-dione-N-oxides, show redox properties close to 1,8diazaanthracene-2,7,9,lO-tetraones, and therefore the cyclic hydroxamic acid unit behaves also as an strong electron acceptor. Voltammetric half-wave fist potentials correlate with the energies of the LUMO in model compounds.
The formation of the mononuclear Pt(II) compound cis-[Pt(NH 3) 2 (Hmtpo-N 3) 2 ](NO 3) 2 ‚2H 2 O ... more The formation of the mononuclear Pt(II) compound cis-[Pt(NH 3) 2 (Hmtpo-N 3) 2 ](NO 3) 2 ‚2H 2 O (1) (Hmtpo) 4,7dihydro-5-methyl-7-oxo[1,2,4]triazolo[1,5-a]pyrimidine) upon reaction of Hmtpo with cisplatin is reported. Subsequent reactions of 1 with Pd(II) electrophiles of the type [Pd(am) 2 (H 2 O) 2 ](NO 3) 2 ((am) 2) en, bpy) in neutral aqueous media afford heterobinuclear complexes of formula [(NH 3) 2 Pt(µ-mtpo-N 3 ,N 4) 2 Pd(am) 2 ](NO 3) 2 , where (am) 2) bpy (2) and en (3). On the other hand, reaction of 1 with the platinum electrophile [Pt(bpy)-(H 2 O) 2 ] 2+ yields the binuclear compound [(mtpo-N 3)(NH 3) 2 Pt(µ-mtpo-N 3 ,N 4)Pt(bpy)(OH)](NO 3)‚6H 2 O (4). The compounds have been structurally characterized by 1-D and 2-D 1 H NMR spectroscopy and X-ray crystallography (1, 2, and 4). Compound 1 crystallizes in the triclinic space group P1 h with unit cell dimensions a) 7.859(1) Å, b) 11.811(2), c) 12.986(2) Å, R) 73.69(1)°,) 84.53(1)°, γ) 85.80(1)°, and Z) 2. Compound 2 crystallizes in the monoclinic space group P2 1 /c with unit cell dimensions a) 13.752(1) Å, b) 12.5658(8) Å, c) 19.215-(1) Å,) 118.08(1)°, and Z) 4. Compound 4 crystallizes in the triclinic space group P1 h with unit cell dimensions a) 10.282(2) Å, b) 14.133(3) Å, c) 14.794(3) Å, R) 110.63(3)°,) 97.83(3)°, γ) 108.48(3)°, and Z) 2. The structure of 1 consists of mononuclear cis-[Pt(NH 3) 2 (Hmtpo-N 3) 2 ] 2+ cations, in which the Hmtpo ligands are coordinated through N(3) in a monodentate fashion. In compound 2, two mtpo moieties bridge the metal centers through N(3) and N(4), giving rise to a Pt-Pd separation of 3.083(1) Å. On the other hand, only one bridging mtpo moiety is present in 4, which accounts for a lengthening in the MM separation to 3.337(1) Å. The environment around the metal centers consists of four nitrogens, except for one Pt nucleus in compound 4, which presents a rare example of a terminal OH group. The 1 H NMR studies show clearly that these structures are retained in solution. Finally, a bidentate bridging mode through N(1)/N(3) is postulated for the species generated in solution by the reaction of 1 with the electrophile [Pt(NH 3) 2 (H 2 O) 2 ] 2+ , which may lead to tetranuclear or polymeric species.
The syntheses of cis-cyclopentane-1,3-dicarboxylic acid, cis-cyclohexane-1,3-dicarboxylic acid, c... more The syntheses of cis-cyclopentane-1,3-dicarboxylic acid, cis-cyclohexane-1,3-dicarboxylic acid, cis-isoaposantenic acid, and cis-apocamphoric acid are described. The key step of each synthesis is the bromine oxidation of an appropriate bicyclic compound in which a 1,3-dimethoxytrimethylene bridge is converted into two cis-carboxyl groups.
A rapid and simple method for the resolution of Z-γ,γ′-di-tert-butyl-D,L-carboxyglutamic acid met... more A rapid and simple method for the resolution of Z-γ,γ′-di-tert-butyl-D,L-carboxyglutamic acid methyl ester is described. The new procedure is based on the enzymatic enantioselective saponification of the methyl ester by the endoprotease papain. Using a simple HPLC protocol the ...
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
In this paper, we analyze the energetic and conformational preferences involved in the chiral dis... more In this paper, we analyze the energetic and conformational preferences involved in the chiral discrimination of ibuprofen (Ibu) isomers by beta-cyclodextrin (b-CD) when forming inclusion complexes in water. This study was performed by means of atomistic molecular mechanics simulations upon four different penetration modes of the guest, and a structural 2D NMR experiment. The trajectories of these simulations were treated with the MM/GBSA method in order to obtain the relative weights of the different free energy components. The resulting values of the free energy of binding and other geometrical features indicate that this chiral selectivity is influenced by a preferred penetration mode involving the S-(C)-Ibu isomer. The calculated DDG of binding is in good agreement with published experiments.
Vicinal 1 H-1 H coupling constants on the backbone carbon chain of several alditol and deoxyaldit... more Vicinal 1 H-1 H coupling constants on the backbone carbon chain of several alditol and deoxyalditol peracetates were calculated with a multiparametric extension of Karplus equation, using conformer distributions and structural information obtained by energy-minimizing all of the rotamers ...
Molecular dynamics (MD) simulations using the Amber force field have been applied to obtain detai... more Molecular dynamics (MD) simulations using the Amber force field have been applied to obtain detailed information on inclusion complex formation between natural cyclodextrins (CDs) and organic molecules (1-alkanols, substituted phenols, and substituted imidazoles). The obtained MD trajectories were used to estimate the binding free energy of each guest/CD complex using the molecular mechanics/Poisson Boltzmann surface area (MM-PBSA) method. The calculated relative binding free energies of the inclusion complexes of some organic compounds with a-and b-CDs were in good agreement with the experimental data though the absolute values were not. Inspection of the binding free energy components revealed the dominant contribution of van der Waals interactions to inclusion complex stability. Both guest-host electrostatic interactions and the hydrophobic effect do also contribute to complex stability. It was also apparent from the calculations that the flexibility of the guest molecule has a significant contribution to complex stability.
The reported rotational barriers about the N-N bond in meso-4,4'-dialkyl-2,2'-dimethyl-l,1 '-bipi... more The reported rotational barriers about the N-N bond in meso-4,4'-dialkyl-2,2'-dimethyl-l,1 '-bipiperidines (1) have been attributed through molecular mechanics calculations to a novel central-bond staggered conformation wherein two sets of a g+g-sequence are inescapably locked to generate a novel situation of unusually high energy.
Langmuir : the ACS journal of surfaces and colloids, Jan 19, 2017
A gold nanoparticle (AuNP) conjugate formed with 11-mercaptoundecanoic acid (MUA) and thiolated p... more A gold nanoparticle (AuNP) conjugate formed with 11-mercaptoundecanoic acid (MUA) and thiolated polyethylene glycol (SH-PEG) is simulated using dissipative particle dynamics (DPD) methods, obtaining an excellent agreement with previous experimental observations. The simulations cover the isolated components (AuNP, MUA, and SH-PEG), as well as pairs of components, and finally the all three components at the same time. In this latter case, changes in the order of addition of MUA and SH-PEG over the AuNP are also considered. The AuNP is formed by independent gold beads and keeps an almost spherical shape throughout the simulation. MUA forms micelles of four to six MUA units when dispersed in water, while SH-PEG stays individually and well solvated. When exposed to AuNP, both molecules show a tendency to form patches on the surface. SH-PEG displays two different conformations (radial and tangential) depending on its relative concentration and the presence of other molecules at the NP su...
The inclusion complexes between 17-α-methyltestosterone (MT) and β-cyclodextrin (bCD) were prepar... more The inclusion complexes between 17-α-methyltestosterone (MT) and β-cyclodextrin (bCD) were prepared and characterized in dissolution and solid phase. The complex promoted a sixfold increment in solubility of the hormone. It has a limited solubility and stoichiometry of 2:1 (bCD:MT) determined by DSC, NMR and solubility experiments, the association constant Ka=2846Lmol-1 and complex fraction of 76% (assessed by DOSY-NMR, in (1:3) DMSO/D2O). The association constant obtained in water by the solubility isotherms is 7540Lmol-1. 2D-ROESY experiments indicate the intermolecular orientation (complete inclusion of the hormone in the cavity). Simulations by molecular dynamics agreed with the formation of the inclusion complex 2:1. Release tests showed the slower release for the complexes, with 50% for lyophilization and 56% for malaxation. These results clearly demonstrate the complexation of MT in bCD, which formulations are promising for further applications involving this steroid in aquaculture, both for sexual reversal and in technologies of hormone in water sequestration.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
The redox propexties of a series of l-azaanthracene-9,10-diones, l$-diazaanthracene-9,10-diones, ... more The redox propexties of a series of l-azaanthracene-9,10-diones, l$-diazaanthracene-9,10-diones, 1 $-diazaanthracene-(lH)2,9,1O-triones and 1,8-diazaanthracene-(lH, 8H)2,7,9,lO-terraones have been studied. The results obtained show that the 2pyridone moiety is a stronger electron acceptor than the pyridine ring, in agreement with reactivity data. 1-Hydroxy-lazaanthracene-2,9,10-triones, synthesized from l-azaanthracene-9,1O-dione-N-oxides, show redox properties close to 1,8diazaanthracene-2,7,9,lO-tetraones, and therefore the cyclic hydroxamic acid unit behaves also as an strong electron acceptor. Voltammetric half-wave fist potentials correlate with the energies of the LUMO in model compounds.
The formation of the mononuclear Pt(II) compound cis-[Pt(NH 3) 2 (Hmtpo-N 3) 2 ](NO 3) 2 ‚2H 2 O ... more The formation of the mononuclear Pt(II) compound cis-[Pt(NH 3) 2 (Hmtpo-N 3) 2 ](NO 3) 2 ‚2H 2 O (1) (Hmtpo) 4,7dihydro-5-methyl-7-oxo[1,2,4]triazolo[1,5-a]pyrimidine) upon reaction of Hmtpo with cisplatin is reported. Subsequent reactions of 1 with Pd(II) electrophiles of the type [Pd(am) 2 (H 2 O) 2 ](NO 3) 2 ((am) 2) en, bpy) in neutral aqueous media afford heterobinuclear complexes of formula [(NH 3) 2 Pt(µ-mtpo-N 3 ,N 4) 2 Pd(am) 2 ](NO 3) 2 , where (am) 2) bpy (2) and en (3). On the other hand, reaction of 1 with the platinum electrophile [Pt(bpy)-(H 2 O) 2 ] 2+ yields the binuclear compound [(mtpo-N 3)(NH 3) 2 Pt(µ-mtpo-N 3 ,N 4)Pt(bpy)(OH)](NO 3)‚6H 2 O (4). The compounds have been structurally characterized by 1-D and 2-D 1 H NMR spectroscopy and X-ray crystallography (1, 2, and 4). Compound 1 crystallizes in the triclinic space group P1 h with unit cell dimensions a) 7.859(1) Å, b) 11.811(2), c) 12.986(2) Å, R) 73.69(1)°,) 84.53(1)°, γ) 85.80(1)°, and Z) 2. Compound 2 crystallizes in the monoclinic space group P2 1 /c with unit cell dimensions a) 13.752(1) Å, b) 12.5658(8) Å, c) 19.215-(1) Å,) 118.08(1)°, and Z) 4. Compound 4 crystallizes in the triclinic space group P1 h with unit cell dimensions a) 10.282(2) Å, b) 14.133(3) Å, c) 14.794(3) Å, R) 110.63(3)°,) 97.83(3)°, γ) 108.48(3)°, and Z) 2. The structure of 1 consists of mononuclear cis-[Pt(NH 3) 2 (Hmtpo-N 3) 2 ] 2+ cations, in which the Hmtpo ligands are coordinated through N(3) in a monodentate fashion. In compound 2, two mtpo moieties bridge the metal centers through N(3) and N(4), giving rise to a Pt-Pd separation of 3.083(1) Å. On the other hand, only one bridging mtpo moiety is present in 4, which accounts for a lengthening in the MM separation to 3.337(1) Å. The environment around the metal centers consists of four nitrogens, except for one Pt nucleus in compound 4, which presents a rare example of a terminal OH group. The 1 H NMR studies show clearly that these structures are retained in solution. Finally, a bidentate bridging mode through N(1)/N(3) is postulated for the species generated in solution by the reaction of 1 with the electrophile [Pt(NH 3) 2 (H 2 O) 2 ] 2+ , which may lead to tetranuclear or polymeric species.
The syntheses of cis-cyclopentane-1,3-dicarboxylic acid, cis-cyclohexane-1,3-dicarboxylic acid, c... more The syntheses of cis-cyclopentane-1,3-dicarboxylic acid, cis-cyclohexane-1,3-dicarboxylic acid, cis-isoaposantenic acid, and cis-apocamphoric acid are described. The key step of each synthesis is the bromine oxidation of an appropriate bicyclic compound in which a 1,3-dimethoxytrimethylene bridge is converted into two cis-carboxyl groups.
A rapid and simple method for the resolution of Z-γ,γ′-di-tert-butyl-D,L-carboxyglutamic acid met... more A rapid and simple method for the resolution of Z-γ,γ′-di-tert-butyl-D,L-carboxyglutamic acid methyl ester is described. The new procedure is based on the enzymatic enantioselective saponification of the methyl ester by the endoprotease papain. Using a simple HPLC protocol the ...
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
In this paper, we analyze the energetic and conformational preferences involved in the chiral dis... more In this paper, we analyze the energetic and conformational preferences involved in the chiral discrimination of ibuprofen (Ibu) isomers by beta-cyclodextrin (b-CD) when forming inclusion complexes in water. This study was performed by means of atomistic molecular mechanics simulations upon four different penetration modes of the guest, and a structural 2D NMR experiment. The trajectories of these simulations were treated with the MM/GBSA method in order to obtain the relative weights of the different free energy components. The resulting values of the free energy of binding and other geometrical features indicate that this chiral selectivity is influenced by a preferred penetration mode involving the S-(C)-Ibu isomer. The calculated DDG of binding is in good agreement with published experiments.
Vicinal 1 H-1 H coupling constants on the backbone carbon chain of several alditol and deoxyaldit... more Vicinal 1 H-1 H coupling constants on the backbone carbon chain of several alditol and deoxyalditol peracetates were calculated with a multiparametric extension of Karplus equation, using conformer distributions and structural information obtained by energy-minimizing all of the rotamers ...
Molecular dynamics (MD) simulations using the Amber force field have been applied to obtain detai... more Molecular dynamics (MD) simulations using the Amber force field have been applied to obtain detailed information on inclusion complex formation between natural cyclodextrins (CDs) and organic molecules (1-alkanols, substituted phenols, and substituted imidazoles). The obtained MD trajectories were used to estimate the binding free energy of each guest/CD complex using the molecular mechanics/Poisson Boltzmann surface area (MM-PBSA) method. The calculated relative binding free energies of the inclusion complexes of some organic compounds with a-and b-CDs were in good agreement with the experimental data though the absolute values were not. Inspection of the binding free energy components revealed the dominant contribution of van der Waals interactions to inclusion complex stability. Both guest-host electrostatic interactions and the hydrophobic effect do also contribute to complex stability. It was also apparent from the calculations that the flexibility of the guest molecule has a significant contribution to complex stability.
The reported rotational barriers about the N-N bond in meso-4,4'-dialkyl-2,2'-dimethyl-l,1 '-bipi... more The reported rotational barriers about the N-N bond in meso-4,4'-dialkyl-2,2'-dimethyl-l,1 '-bipiperidines (1) have been attributed through molecular mechanics calculations to a novel central-bond staggered conformation wherein two sets of a g+g-sequence are inescapably locked to generate a novel situation of unusually high energy.
Langmuir : the ACS journal of surfaces and colloids, Jan 19, 2017
A gold nanoparticle (AuNP) conjugate formed with 11-mercaptoundecanoic acid (MUA) and thiolated p... more A gold nanoparticle (AuNP) conjugate formed with 11-mercaptoundecanoic acid (MUA) and thiolated polyethylene glycol (SH-PEG) is simulated using dissipative particle dynamics (DPD) methods, obtaining an excellent agreement with previous experimental observations. The simulations cover the isolated components (AuNP, MUA, and SH-PEG), as well as pairs of components, and finally the all three components at the same time. In this latter case, changes in the order of addition of MUA and SH-PEG over the AuNP are also considered. The AuNP is formed by independent gold beads and keeps an almost spherical shape throughout the simulation. MUA forms micelles of four to six MUA units when dispersed in water, while SH-PEG stays individually and well solvated. When exposed to AuNP, both molecules show a tendency to form patches on the surface. SH-PEG displays two different conformations (radial and tangential) depending on its relative concentration and the presence of other molecules at the NP su...
The inclusion complexes between 17-α-methyltestosterone (MT) and β-cyclodextrin (bCD) were prepar... more The inclusion complexes between 17-α-methyltestosterone (MT) and β-cyclodextrin (bCD) were prepared and characterized in dissolution and solid phase. The complex promoted a sixfold increment in solubility of the hormone. It has a limited solubility and stoichiometry of 2:1 (bCD:MT) determined by DSC, NMR and solubility experiments, the association constant Ka=2846Lmol-1 and complex fraction of 76% (assessed by DOSY-NMR, in (1:3) DMSO/D2O). The association constant obtained in water by the solubility isotherms is 7540Lmol-1. 2D-ROESY experiments indicate the intermolecular orientation (complete inclusion of the hormone in the cavity). Simulations by molecular dynamics agreed with the formation of the inclusion complex 2:1. Release tests showed the slower release for the complexes, with 50% for lyophilization and 56% for malaxation. These results clearly demonstrate the complexation of MT in bCD, which formulations are promising for further applications involving this steroid in aquaculture, both for sexual reversal and in technologies of hormone in water sequestration.
Uploads
Papers by Carlos Jaime