Karilys Gonzalez | University of Puerto Rico, Carolina (original) (raw)
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Acta Crystallographica Section E-structure Reports Online, Nov 28, 2012
The title compound, C 26 H 42 ClNO 2 , is a 3-chloro steroid with a Weinreb amide at the C-24 pos... more The title compound, C 26 H 42 ClNO 2 , is a 3-chloro steroid with a Weinreb amide at the C-24 position. The two cyclohexane and the cyclohexene rings adopt chair and boat conformations, respectively. The cyclopentane ring has an envelope conformation. Related literature The title compound was obtained as part of our studies on the synthesis of chlorinated steroids as antimalarial agents. For chlorination of 3-hydroxyl-5-Á steroids, see: Liu et al. (2005). For antimalarial steroids, see: Corrales et al. (2011); Sharma et al. (2008). For the emerging role of chlorinated lipids and fatty acids in pathology, see: Spickett (2007). For the use of steryl chlorides as synthetic intermediates, see: Ochi et al. (1977). For liquid crystal properties of steryl chlorides, see: Leder (1971). For chloroquine-resistant malaria, see: Wellems & Plowe (2001). For drug resistance in malaria, see: Bloland (2001).
Tetrahedron Letters, Dec 1, 2012
The Caribbean mollusc Dolabrifera dolabrifera from Puerto Rico contains two new propionatederived... more The Caribbean mollusc Dolabrifera dolabrifera from Puerto Rico contains two new propionatederived metabolites, dolabriferol B and C (2 and 3), in addition to the known compound dolabriferol (1). The structures of dolabriferol B (2) and C (3) were established by comparison of their spectral data with those of 1, and the absolute configuration of 2 was determined from chemical degradation studies. The structure of dolabriferol C (3) was confirmed by X-ray analysis.
![Research paper thumbnail of Crystal structure of a nickel compound comprising two nickel(II) complexes with different ligand environments: [Ni(tren)(H2O)2][Ni(H2O)6](SO4)2](https://attachments.academia-assets.com/104051414/thumbnails/1.jpg)
](Acta Crystallographica Section E Crystallographic Communications, 2020
The title compound, diaqua[tris(2-aminoethyl)amine]nickel(II) hexaaquanickel(II) bis(sulfate), [N... more The title compound, diaqua[tris(2-aminoethyl)amine]nickel(II) hexaaquanickel(II) bis(sulfate), [Ni(C6H18N4)(H2O)2][Ni(H2O)6](SO4)2 or [Ni(tren)(H2O)2][Ni(H2O)6](SO4)2, consists of two octahedral nickel complexes within the same unit cell. These metal complexes are formed from the reaction of [Ni(H2O)6](SO4) and the ligand tris(2-aminoethyl)amine (tren). The crystals of the title compound are purple, different from those of the starting complex [Ni(H2O)6](SO4), which are turquoise. The reaction was performed both in a 1:1 and 1:2 metal–ligand molar ratio, always yielding the co-precipitation of the two types of crystals. The asymmetric unit of the title compound, which crystallizes in the space group Pnma, consists of two half NiII complexes and a sulfate counter-anion. The mononuclear cationic complex [Ni(tren)(H2O)2]2+ comprises an Ni ion, the tren ligand and two water molecules, while the mononuclear complex [Ni(H2O)6]2+ consists of another Ni ion surrounded by six coordinated wat...
Tetrahedron Letters, 2012
Journal of Controlled Release, 2003
Protein inactivation and aggregation are serious drawbacks in the encapsulation of proteins in bi... more Protein inactivation and aggregation are serious drawbacks in the encapsulation of proteins in bioerodible polymers by water-in-oil-in-water (w/o/w) encapsulation. The model protein alpha-chymotrypsin was employed to investigate whether its stabilization towards the major stress factors in the w/o/w encapsulation procedure would allow for the encapsulation and release of non-aggregated and active protein. Due to the formation of amorphous aggregates alpha-chymotrypsin is an excellent sensor to probe unfolding events. Furthermore, its enzymatic activity is highly sensitive towards the presence of organic solvents. alpha-Chymotrypsin in aqueous solution showed substantial aggregation and activity loss when it was homogenized with CH(2)Cl(2) due to adsorption to the interface. Its w/o/w encapsulation in poly(lactic-co-glycolic)acid (PLGA) microspheres caused formation of 35% non-covalent aggregates and reduced the specific activity by 14%. Screening for efficient excipients revealed that co-dissolving the protein with maltose and polyethylene glycol (PEG, M(w) 5000) in the first aqueous phase reduced interface-induced protein aggregation and inactivation. Employing these excipients during encapsulation led to a reduction in alpha-chymotrypsin inactivation (10%) and aggregation (12%). Optimizing the effect of PEG by also dissolving the excipient in the organic phase prior to encapsulation further decreased the amount of non-covalent aggregates to 7% and loss in activity to 5%. The data obtained demonstrate that the w/o emulsification step is the main stress-factor in the w/o/w encapsulation procedure but subsequent encapsulation steps also cause some protein aggregation.
Acta Crystallographica Section E Structure Reports Online, 2012
The title compound, C 26 H 42 ClNO 2 , is a 3-chloro steroid with a Weinreb amide at the C-24 pos... more The title compound, C 26 H 42 ClNO 2 , is a 3-chloro steroid with a Weinreb amide at the C-24 position. The two cyclohexane and the cyclohexene rings adopt chair and boat conformations, respectively. The cyclopentane ring has an envelope conformation. Related literature The title compound was obtained as part of our studies on the synthesis of chlorinated steroids as antimalarial agents. For chlorination of 3-hydroxyl-5-Á steroids, see: Liu et al. (2005). For antimalarial steroids, see: Corrales et al. (2011); Sharma et al. (2008). For the emerging role of chlorinated lipids and fatty acids in pathology, see: Spickett (2007). For the use of steryl chlorides as synthetic intermediates, see: Ochi et al. (1977). For liquid crystal properties of steryl chlorides, see: Leder (1971). For chloroquine-resistant malaria, see: Wellems & Plowe (2001). For drug resistance in malaria, see: Bloland (2001). Experimental Crystal data C 26 H 42 ClNO 2 M r = 436.06 Orthorhombic, P2 1 2 1 2 1 a = 7.5263 (2) Å b = 16.2157 (4) Å c = 20.8850 (5) Å V = 2548.89 (11) Å 3 Z = 4 Mo K radiation = 0.17 mm À1 T = 296 K 0.31 Â 0.09 Â 0.08 mm Data collection Bruker APEXII CCD diffractometer Absorption correction: multi-scan (SADABS; Sheldrick, 2008a) T min = 0.949, T max = 0.987 23203 measured reflections 6244 independent reflections 3307 reflections with I > 2(I) R int = 0.035 Refinement R[F 2 > 2(F 2)] = 0.056 wR(F 2) = 0.157 S = 1.01 6244 reflections 276 parameters H-atom parameters constrained Á max = 0.19 e Å À3 Á min = À0.14 e Å À3 Absolute structure: Flack (1983), 2662 Friedel pairs Flack parameter: À0.04 (9) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: FY2071).
Angewandte Chemie, 2019
The P-and M-enantiomers of the octanuclear [Fe8(μ4-O)4(μ-4-Cl-pz)12Cl4]complex of T-symmetry were... more The P-and M-enantiomers of the octanuclear [Fe8(μ4-O)4(μ-4-Cl-pz)12Cl4]complex of T-symmetry were resolved by temporary substitution of chloride ligands by racemic 4-s Buphenolates and crystallization, where the Sand R-phenolates coordinate selectively to the M-and P-complexes, respectively, as shown by circular dichroism analysis and absolute X-ray structure determination. This constitutes a rare example of enantiomeric recognition resulting in spontaneous resolution upon crystallization.
The P and M enantiomers of the octanuclear [Fe 8-(m 4-O) 4 (m-4-Cl-pz) 12 Cl 4 ] complex, having ... more The P and M enantiomers of the octanuclear [Fe 8-(m 4-O) 4 (m-4-Cl-pz) 12 Cl 4 ] complex, having T symmetry, were resolved by temporary substitution of chloride ligands by racemic 4-s Bu-phenolates and subsequent crystallization, where the (S)-and (R)-phenolates coordinate selectively to the M and P complexes, respectively. The complexes were characterized by circular dichroism analysis and X-ray structure determination. This work constitutes a rare example of enantiomeric recognition resulting in spontaneous resolution upon crystallization. Interest in the resolution of racemic mixtures stems from the importance of enantiopure substances to biological processes and the pharmaceutical industry. [1] Enantiopure materials have also applications in magnetics and nonlinear optics. [2, 3] While synthetic asymmetric molecules abound, in the absence of a chiral initiator only their racemic mixtures are synthesized , with the notable exemption of asymmetric autocatal-ysis. [4] The latter may in some cases resolve spontaneously by crystallization, yielding enantiopure single crystals. Chiral stationary phase chromatographic separation and attrition-enhanced deracemization are currently the principal resolution methods. [5, 6] Enantioselective synthetic techniques employing chiral catalysts have been developed to circumvent the difficult problem of racemate resolution. [7] The 2001 Nobel prize was awarded for the development of chiral catalysts, [8] a field that remains active and vibrant to date. [9] Most homogeneous racemic catalysts are transition-metal complexes, which can undergo facile isomerization, because of the lability of metal-ligand bonds and flexibility of their coordination sphere (e.g., Berry pseudo-rotation, Bailar twist). In contrast, successful chiral transition-metal catalysts, such as the family of Chiralphos, [10] contain ligands whose steric bulk renders them inflexible, preventing racemization. However, ligand lability can still be a problem, and is further exacerbated for metal ions with low or no crystal field stabilization (e.g., high-spin d 5 centers). Unfortunately, this list includes Fe 3+ complexes whose extensive role in homogeneous catalysis has been recognized for a long time. [9d, 11] Clearly, the field of specialty chiral chemicals stands to benefit from the availability of new, nonracemizable Fe 3+ enantiopure compounds. Examples of mononuclear transition-metal complex race-mates that have been successfully resolved are rare. For instance, monomeric ruthenium complexes containing the 1-Me-3PhCp ligand were resolved by temporary substitution of a terminal chloride ligand by (S)-a-methylbenzenemethane-thiol and subsequent fractional crystallization to isolate the two enantiomers of the complex. [12] A similar approach was used for the resolution of rhodium complexes with tripodal tetradentate ligands, employing (S)-phenylglycinato as the resolving agent. [9] Chromatographic methods have been also utilized for the resolution of metal complexes. [13] In contrast to mononuclear species, the racemization of polynuclear complexes, requiring the simultaneous rearrangement of the coordination spheres of every component metal center, adding up to a higher activation energy, is a more unlikely process. The resolution of tetrahedral M 4 L 6 metal-ligand hosts made of labile components (M = Ga III , Fe III , Al III , In III , Ti IV , Ge IV), including a water-soluble derivative, has been demonstrated. [14] It follows then that, conceptually, racemic poly-nuclear complexes may be an easier target for resolution, even if they involve somewhat labile metal cations. The area of chiral metal cluster and nanoparticle applications in catalysis has been recently reviewed and the need for further development of the field has been stressed. [15] We have characterized a family of octanuclear Fe 3+ complexes of the general formula [Fe 8 (m 4-O) 4 (m-4-R-pz) 12 X 4 ], [Fe 8 ] (Figure 1 a), where pz = pyrazolato anion
Acta Crystallographica Section E-structure Reports Online, Nov 28, 2012
The title compound, C 26 H 42 ClNO 2 , is a 3-chloro steroid with a Weinreb amide at the C-24 pos... more The title compound, C 26 H 42 ClNO 2 , is a 3-chloro steroid with a Weinreb amide at the C-24 position. The two cyclohexane and the cyclohexene rings adopt chair and boat conformations, respectively. The cyclopentane ring has an envelope conformation. Related literature The title compound was obtained as part of our studies on the synthesis of chlorinated steroids as antimalarial agents. For chlorination of 3-hydroxyl-5-Á steroids, see: Liu et al. (2005). For antimalarial steroids, see: Corrales et al. (2011); Sharma et al. (2008). For the emerging role of chlorinated lipids and fatty acids in pathology, see: Spickett (2007). For the use of steryl chlorides as synthetic intermediates, see: Ochi et al. (1977). For liquid crystal properties of steryl chlorides, see: Leder (1971). For chloroquine-resistant malaria, see: Wellems & Plowe (2001). For drug resistance in malaria, see: Bloland (2001).
Tetrahedron Letters, Dec 1, 2012
The Caribbean mollusc Dolabrifera dolabrifera from Puerto Rico contains two new propionatederived... more The Caribbean mollusc Dolabrifera dolabrifera from Puerto Rico contains two new propionatederived metabolites, dolabriferol B and C (2 and 3), in addition to the known compound dolabriferol (1). The structures of dolabriferol B (2) and C (3) were established by comparison of their spectral data with those of 1, and the absolute configuration of 2 was determined from chemical degradation studies. The structure of dolabriferol C (3) was confirmed by X-ray analysis.
Acta Crystallographica Section E Crystallographic Communications, 2020
The title compound, diaqua[tris(2-aminoethyl)amine]nickel(II) hexaaquanickel(II) bis(sulfate), [N... more The title compound, diaqua[tris(2-aminoethyl)amine]nickel(II) hexaaquanickel(II) bis(sulfate), [Ni(C6H18N4)(H2O)2][Ni(H2O)6](SO4)2 or [Ni(tren)(H2O)2][Ni(H2O)6](SO4)2, consists of two octahedral nickel complexes within the same unit cell. These metal complexes are formed from the reaction of [Ni(H2O)6](SO4) and the ligand tris(2-aminoethyl)amine (tren). The crystals of the title compound are purple, different from those of the starting complex [Ni(H2O)6](SO4), which are turquoise. The reaction was performed both in a 1:1 and 1:2 metal–ligand molar ratio, always yielding the co-precipitation of the two types of crystals. The asymmetric unit of the title compound, which crystallizes in the space group Pnma, consists of two half NiII complexes and a sulfate counter-anion. The mononuclear cationic complex [Ni(tren)(H2O)2]2+ comprises an Ni ion, the tren ligand and two water molecules, while the mononuclear complex [Ni(H2O)6]2+ consists of another Ni ion surrounded by six coordinated wat...
Tetrahedron Letters, 2012
Journal of Controlled Release, 2003
Protein inactivation and aggregation are serious drawbacks in the encapsulation of proteins in bi... more Protein inactivation and aggregation are serious drawbacks in the encapsulation of proteins in bioerodible polymers by water-in-oil-in-water (w/o/w) encapsulation. The model protein alpha-chymotrypsin was employed to investigate whether its stabilization towards the major stress factors in the w/o/w encapsulation procedure would allow for the encapsulation and release of non-aggregated and active protein. Due to the formation of amorphous aggregates alpha-chymotrypsin is an excellent sensor to probe unfolding events. Furthermore, its enzymatic activity is highly sensitive towards the presence of organic solvents. alpha-Chymotrypsin in aqueous solution showed substantial aggregation and activity loss when it was homogenized with CH(2)Cl(2) due to adsorption to the interface. Its w/o/w encapsulation in poly(lactic-co-glycolic)acid (PLGA) microspheres caused formation of 35% non-covalent aggregates and reduced the specific activity by 14%. Screening for efficient excipients revealed that co-dissolving the protein with maltose and polyethylene glycol (PEG, M(w) 5000) in the first aqueous phase reduced interface-induced protein aggregation and inactivation. Employing these excipients during encapsulation led to a reduction in alpha-chymotrypsin inactivation (10%) and aggregation (12%). Optimizing the effect of PEG by also dissolving the excipient in the organic phase prior to encapsulation further decreased the amount of non-covalent aggregates to 7% and loss in activity to 5%. The data obtained demonstrate that the w/o emulsification step is the main stress-factor in the w/o/w encapsulation procedure but subsequent encapsulation steps also cause some protein aggregation.
Acta Crystallographica Section E Structure Reports Online, 2012
The title compound, C 26 H 42 ClNO 2 , is a 3-chloro steroid with a Weinreb amide at the C-24 pos... more The title compound, C 26 H 42 ClNO 2 , is a 3-chloro steroid with a Weinreb amide at the C-24 position. The two cyclohexane and the cyclohexene rings adopt chair and boat conformations, respectively. The cyclopentane ring has an envelope conformation. Related literature The title compound was obtained as part of our studies on the synthesis of chlorinated steroids as antimalarial agents. For chlorination of 3-hydroxyl-5-Á steroids, see: Liu et al. (2005). For antimalarial steroids, see: Corrales et al. (2011); Sharma et al. (2008). For the emerging role of chlorinated lipids and fatty acids in pathology, see: Spickett (2007). For the use of steryl chlorides as synthetic intermediates, see: Ochi et al. (1977). For liquid crystal properties of steryl chlorides, see: Leder (1971). For chloroquine-resistant malaria, see: Wellems & Plowe (2001). For drug resistance in malaria, see: Bloland (2001). Experimental Crystal data C 26 H 42 ClNO 2 M r = 436.06 Orthorhombic, P2 1 2 1 2 1 a = 7.5263 (2) Å b = 16.2157 (4) Å c = 20.8850 (5) Å V = 2548.89 (11) Å 3 Z = 4 Mo K radiation = 0.17 mm À1 T = 296 K 0.31 Â 0.09 Â 0.08 mm Data collection Bruker APEXII CCD diffractometer Absorption correction: multi-scan (SADABS; Sheldrick, 2008a) T min = 0.949, T max = 0.987 23203 measured reflections 6244 independent reflections 3307 reflections with I > 2(I) R int = 0.035 Refinement R[F 2 > 2(F 2)] = 0.056 wR(F 2) = 0.157 S = 1.01 6244 reflections 276 parameters H-atom parameters constrained Á max = 0.19 e Å À3 Á min = À0.14 e Å À3 Absolute structure: Flack (1983), 2662 Friedel pairs Flack parameter: À0.04 (9) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: FY2071).
Angewandte Chemie, 2019
The P-and M-enantiomers of the octanuclear [Fe8(μ4-O)4(μ-4-Cl-pz)12Cl4]complex of T-symmetry were... more The P-and M-enantiomers of the octanuclear [Fe8(μ4-O)4(μ-4-Cl-pz)12Cl4]complex of T-symmetry were resolved by temporary substitution of chloride ligands by racemic 4-s Buphenolates and crystallization, where the Sand R-phenolates coordinate selectively to the M-and P-complexes, respectively, as shown by circular dichroism analysis and absolute X-ray structure determination. This constitutes a rare example of enantiomeric recognition resulting in spontaneous resolution upon crystallization.
The P and M enantiomers of the octanuclear [Fe 8-(m 4-O) 4 (m-4-Cl-pz) 12 Cl 4 ] complex, having ... more The P and M enantiomers of the octanuclear [Fe 8-(m 4-O) 4 (m-4-Cl-pz) 12 Cl 4 ] complex, having T symmetry, were resolved by temporary substitution of chloride ligands by racemic 4-s Bu-phenolates and subsequent crystallization, where the (S)-and (R)-phenolates coordinate selectively to the M and P complexes, respectively. The complexes were characterized by circular dichroism analysis and X-ray structure determination. This work constitutes a rare example of enantiomeric recognition resulting in spontaneous resolution upon crystallization. Interest in the resolution of racemic mixtures stems from the importance of enantiopure substances to biological processes and the pharmaceutical industry. [1] Enantiopure materials have also applications in magnetics and nonlinear optics. [2, 3] While synthetic asymmetric molecules abound, in the absence of a chiral initiator only their racemic mixtures are synthesized , with the notable exemption of asymmetric autocatal-ysis. [4] The latter may in some cases resolve spontaneously by crystallization, yielding enantiopure single crystals. Chiral stationary phase chromatographic separation and attrition-enhanced deracemization are currently the principal resolution methods. [5, 6] Enantioselective synthetic techniques employing chiral catalysts have been developed to circumvent the difficult problem of racemate resolution. [7] The 2001 Nobel prize was awarded for the development of chiral catalysts, [8] a field that remains active and vibrant to date. [9] Most homogeneous racemic catalysts are transition-metal complexes, which can undergo facile isomerization, because of the lability of metal-ligand bonds and flexibility of their coordination sphere (e.g., Berry pseudo-rotation, Bailar twist). In contrast, successful chiral transition-metal catalysts, such as the family of Chiralphos, [10] contain ligands whose steric bulk renders them inflexible, preventing racemization. However, ligand lability can still be a problem, and is further exacerbated for metal ions with low or no crystal field stabilization (e.g., high-spin d 5 centers). Unfortunately, this list includes Fe 3+ complexes whose extensive role in homogeneous catalysis has been recognized for a long time. [9d, 11] Clearly, the field of specialty chiral chemicals stands to benefit from the availability of new, nonracemizable Fe 3+ enantiopure compounds. Examples of mononuclear transition-metal complex race-mates that have been successfully resolved are rare. For instance, monomeric ruthenium complexes containing the 1-Me-3PhCp ligand were resolved by temporary substitution of a terminal chloride ligand by (S)-a-methylbenzenemethane-thiol and subsequent fractional crystallization to isolate the two enantiomers of the complex. [12] A similar approach was used for the resolution of rhodium complexes with tripodal tetradentate ligands, employing (S)-phenylglycinato as the resolving agent. [9] Chromatographic methods have been also utilized for the resolution of metal complexes. [13] In contrast to mononuclear species, the racemization of polynuclear complexes, requiring the simultaneous rearrangement of the coordination spheres of every component metal center, adding up to a higher activation energy, is a more unlikely process. The resolution of tetrahedral M 4 L 6 metal-ligand hosts made of labile components (M = Ga III , Fe III , Al III , In III , Ti IV , Ge IV), including a water-soluble derivative, has been demonstrated. [14] It follows then that, conceptually, racemic poly-nuclear complexes may be an easier target for resolution, even if they involve somewhat labile metal cations. The area of chiral metal cluster and nanoparticle applications in catalysis has been recently reviewed and the need for further development of the field has been stressed. [15] We have characterized a family of octanuclear Fe 3+ complexes of the general formula [Fe 8 (m 4-O) 4 (m-4-R-pz) 12 X 4 ], [Fe 8 ] (Figure 1 a), where pz = pyrazolato anion