Manuel A. Fernandes

University of the Witwatersrand, Johannesburg, Gauteng, South Africa

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Publications (174)301.67 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The kinetics of the substitution of H2O on Co(III) in aquacobalamin (H2OCbl+, vitamin B12a) and in a Co(III) corrole analogue of B12a, aqua-[10-(2-[[4-(1H-imidazol-1-yl-methyl)benzoyl]amino]phenyl)-5,15-diphenylcorrolato]-cobalt(III), [H2O-DPTC-Co], were determined in 80:20 MeOH/H2O and low ionic strength. The second order rate constant kII(25 °C) for the reaction of H2OCbl+ is 2720 M− 1 s− 1 (ΔH‡ = 82(5) kJ mol− 1 and ΔS‡ = 96(19) J K− 1 mol− 1) while for [H2O-DPTC-Co], kII(25 °C) = 990 M− 1 s− 1 (ΔH‡ = 41(1) kJ mol− 1 and ΔS‡ = − 50(3) J K− 1 mol− 1). It is argued that differences in ΔS‡ are due to differential solvent electrostriction, arising from the different charges at the metal center in the two complexes. A smaller ΔH‡ for the reaction with [H2O-DPTC-Co] suggests that the transition state occurs earlier along the reaction coordinate, consistent with the higher affinity of Co(III) for CN− in the corrole. On this basis only, Co(III) is more labile towards CN− in the corrole than in the corrin. However, because of differences in ΔS‡, H2OCbl+ is more labile towards CN− than [H2O-DPTC-Co] above the isokinetic temperature of 8 °C. The nature of the equatorial ligand in Co(III) macrocyclic complexes significantly affects the lability of the metal ion.
    Inorganic Chemistry Communications 07/2015; 57. DOI:10.1016/j.inoche.2015.04.013 · 2.06 Impact Factor
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    ABSTRACT: The chloride intracellular channel protein, CLIC1, is synthesised as a soluble monomer that can reversibly bind membranes. Soluble CLIC1 is proposed to respond to the low pH found at a membrane surface by partially unfolding and restructuring into a membrane-competent conformation. This transition is proposed to be controlled by strategically located "pH-sensor" residues that become protonated at acidic pH. In this study, we investigate the role of two conserved glutamate residues, Glu85 in the N-domain and Glu228 in the C-domain, as pH-sensors. E85L and E228L CLIC1 variants were created to reduce pH sensitivity by permanently breaking the bonds these residues form. The structure and stability of each variant was compared to the wild type at both pH 7.0 and pH 5.5. Neither substitution significantly altered the structure but both decreased the conformational stability. Furthermore, E85L CLIC1 formed a urea-induced unfolding intermediate state at both pH 7 and pH 5.5 compared to wild-type and E228L CLIC1 which only formed the intermediate at pH 5.5. We conclude that Glu85 and Glu228 are two of the five pH-sensor residues of CLIC1 and contribute to the pH-response in different ways. Glu228 lowers the stability of the native state at pH 5.5, while Glu85 contributes both to the stability of the native state and to the formation of the intermediate state. By putting these interactions into the context of the three previously described CLIC1 pH-sensor residues, we propose a mechanism for the conversion of CLIC1 from the soluble state to the pre-membrane form.
    Molecular and Cellular Biochemistry 09/2014; 398(1-2). DOI:10.1007/s11010-014-2207-z · 2.39 Impact Factor
  • Richard M. Mampa, Manuel A. Fernandes, Laurence Carlton
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    ABSTRACT: The complexes [Fe(Cp)(SnPh3)(CO)(PR3)] (PR3 = PMe3 (1), PnBu3 (2), PCy3 (3), PMe2Ph (4), PMePh2 (5), P(CH2Ph)3 (6), PPh3 (7), P(4-MeC6H4)3 (8), P(4-MeOC6H4)3 (9), P(4-FC6H4)3 (10), P(4-CF3C6H4)3 (11), P(NMe2)3 (12), P(OMe)3 (13), P(OPh)3 (14)), which have been characterized by X-ray crystallography (except for 1 and 4), infrared spectroscopy (carbonyl stretching frequency, νCO), and NMR spectroscopy (13C, 31P, 57Fe, 119Sn) offer some insight into the response of the iron nucleus to changes in the electronic and steric properties of the PR3 ligand. A fairly good correlation is found between the 57Fe chemical shift and the Tolman cone angle θ for PR3 and a rather poorer correlation between δ(57Fe) and νCO. However, for the subseries of complexes 7-11 having PR3 = P(4-XC6H4)3 (X = H, Me, MeO, F, CF3), the correlation between δ(57Fe) and νCO is very good. Since the steric properties of these ligands, from the point of view of the metal, are identical (θ = 145°), this provides a means of separating the steric and electronic contributions of PR3 to δ(57Fe). The electronic contribution of PR3 to δ(57Fe) can be further separated into σ and π components by making use of the finding that the π component of the Fe-P bond has a negligible influence on δ(57Fe), unlike its influence on νCO. The ligands PMe3, PnBu3, PCy3, PMe2Ph, PMePh2, and P(NMe2)3 are found to be “pure” σ donors, P(OMe)3 and P(OPh)3 are found to be π acceptors of differing strength, and P(4-XC6H4)3 is found to show weak but clearly distinguishable π acceptor properties.
    Organometallics 06/2014; 33(13):140626113119005. DOI:10.1021/om4011593 · 4.25 Impact Factor
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    ABSTRACT: An acyclic amino alcohol compound (1) and its protonated form (2) are investigated as solid state synthons for the design of self-assembled columnar structures. Compound 1, C-16 H-33 N-3 O-2, crystallizes in double-stranded chains comprising ill-defined, collapsed central cavities. Chains in (1) are further linked by stereospecific O-H center dot center dot center dot N interactions to form porous sheets. Well-defined central cavities are observed in the columnar structure of compound 2, C-16 H-36 Cl-3 N-3 O-14. The larger cavities result from a reorientation of N-H center dot center dot center dot O and hydroxycyclohexyl O-H center dot center dot center dot O hydrogen-bonding interactions effected by protonation of nitrogen atoms. The nature and size of the central cavity observed for an amino alcohol compound (1), C-16 H-33 N-3 O-2, is modulated by altering the hydrogen bonding array. Heteroatom protonation and anion inclusion redirect hydrogen bonding interactions of amino alcohol moieties and their bridging trans dialkylammonium chains, that result in the formation of well-defined central cavities observed in compound (2), C-16 H-36 Cl-3 N-3 O-14.
    Journal of Chemical Crystallography 05/2014; 44(5):229-235. DOI:10.1007/s10870-014-0505-7 · 0.48 Impact Factor
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    ABSTRACT: The synthesis of a Co(III) corrole, [10-(2-[[4-(1H-imidazol-1-ylmethyl)benzoyl]amino]phenyl)-5,15-diphenylcorrolato]cobalt(III), DPTC-Co, bearing a tail motif terminating in an imidazole ligand that coordinates Co(III), is described. The corrole therefore places Co(III) in a similar environment to that in aquacobalamin (vitamin B12a, H2OCbl(+)) but with a different equatorial ligand. In coordinating solvents, DPTC-Co is a mixture of five- and six-coordinate species, with a solvent molecule occupying the axial coordination site trans to the proximal imidazole ligand. In an 80:20 MeOH/H2O solution, allowed to age for about 1 h, the predominant species is the six-coordinate aqua species [H2O-DPTC-Co]. It is monomeric at least up to concentrations of 60 μM. The coordinated H2O has a pKa = 9.76(6). Under the same conditions H2OCbl(+) has a pKa = 7.40(2). Equilibrium constants for the substitution of coordinated H2O by exogenous ligands are reported as log K values for neutral N-, P-, and S-donor ligands, and CN(-), NO2(-), N3(-), SCN(-), I(-), and Cys in 80:20 MeOH/H2O solution at low ionic strength. The log K values for [H2O-DPTC-Co] correlate reasonably well with those for H2OCbl(+); therefore, Co(III) displays a similar behavior toward these ligands irrespective of whether the equatorial ligand is a corrole or a corrin. Pyridine is an exception; it is poorly coordinated by H2OCbl(+) because of the sterically hindered coordination site of the corrin. With few exceptions, [H2O-DPTC-Co] has a higher affinity for neutral ligands than H2OCbl(+), but the converse is true for anionic ligands. Density functional theory (DFT) models (BP86/TZVP) show that the Co-ligand bonds tend to be longer in corrin than in corrole complexes, explaining the higher affinity of the latter for neutral ligands. It is argued that the residual charge at the metal center (+2 in corrin, 0 in corrole) increases the affinity of H2OCbl(+) for anionic ligands through an electrostatic attraction. The topological properties of the electron density in the DFT-modeled compounds are used to explore the nature of the bonding between the metal and the ligands.
    Inorganic Chemistry 04/2014; 53(9). DOI:10.1021/ic5000793 · 4.79 Impact Factor
  • Terisha Rampersadh, Manuel A. Fernandes, Laurence Carlton
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    ABSTRACT: Abstract The X-ray structures of the complexes [Ir(8OQ)(1,5-cod)] (1), [Ir(8OQd)(1,5-cod)] (2) and [Ir2(μ-7AI)2(1,5-cod)2] (3) (where 8OQ, 8OQd and 7AI are anions derived from 8-hydroxyquinoline, 2-methyl-8-hydroxyquinoline (8-hydroxyquinaldine) and 7-azaindole, respectively) are mononuclear in the case of 1 and 2, with evidence of steric strain induced by the methyl group in 2 and dinuclear in the case of 3. The oxidative addition products [Ir(8OQd)(H)(EPh3)(1,5-cod)] [E = Si (4), Sn (5)], formed by the reaction of 2 with SiHPh3 and SnHPh3, respectively, show significant conformational differences in the solid state. Graphical Abstract The complex cyclooctadieneiridium(I) 2-methyl-8-oxyquinolinate shows conformational isomerism as do adducts formed by its reaction with triphenylsilane and triphenyltin hydride.
    Journal of Chemical Crystallography 03/2014; 44(3):151-160. DOI:10.1007/s10870-014-0495-5 · 0.48 Impact Factor
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    ABSTRACT: In order to investigate possible isostructural solid solutions of disubstituted N-phenylformamides and thioamides, we have studied the re-crystallization of pairs of compounds selected from 2,6-difluoro-N-phenylformamide (I), 2,6-dichloro-N-phenylformamide (II), 2,6-dimethyl-N-phenylformamide (III), 2,6-dichloro-N-phenylthioamide (IV), 2,6-dimethyl-N-phenylthioamide (V), 2,6-diisopropyl-N-phenylformamide (VI) and 2,6-diisopropyl-N-phenylthioamide (VII). For single-component 2,6-disubstituted-N-phenylformamides only the trans form occurs in the pure crystal, while for thioamides the cis form occurs, with only one exception. By forming solid solutions of pairs of these molecules the resulting structures all adopt similar N-H...O/S chains in the crystals. Solid solutions (1), (2) and (3), resulting from the mixing of (I) and (II), (II) and (III), and (IV) and (V), respectively, are all isostructural with each other (space group Pbca). Only co-crystal (1) is isostructural to both starting materials, while (2) is isostructural to only one of the starting pair, (II). Solid solution (3), which adopts the same Pbca structure as (1) and (2), is different to the monoclinic structures of both the reactants. Solid solution (4) is monoclinic, with similar hydrogen-bonded chains, and isostructural to the two components, resulting from the composition from the mixing of (VI) and (VII). Isostructural indices were used to quantify crystal-packing similarities and differences. Occupancy factors of the reactants in each co-crystal differ widely.
    02/2014; 70(Pt 1):106-114. DOI:10.1107/S2052520613022129
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    ABSTRACT: In this work, 2-((2-((2-hydroxyethyl)amino)ethyl)amino)cyclohexanol, HEAC, was prepared in solvent by the ring opening of cyclohexene oxide with 2-(2-amino-ethylamino)ethanol. Four complexes of HEAC, including [Pd(HEAC)Cl2] (1), [Cd2(HEAC)2(μ-Br)2Br2] (2), [Cd(HEAC)(OAc)2] (3) and [Hg(HEAC)Cl2] (4), were prepared and identified by elemental analysis, FT-IR, Raman, 1H NMR spectroscopy and single-crystal X-ray diffraction. Redox properties of HEAC before and after complexation were investigated in DMSO. In the crystal structure of HEAC, the two hydroxyl arms are trans to each other and the cyclohexane ring has a chair conformation with two C-chiral centers. Two new N-chiral centers are produced during the complexation process. In the crystal structure of 1, the palladium atom has a distorted square planar PdN2Cl2 environment. X-ray analysis of 2 reveals a dimer structure containing two bromide bridges. Each cadmium atom in 2 is found to be in a CdN2OBr3 distorted octahedral environment. The Cd2(μ-Br)2 moiety is placed on a plane and forms a parallelogram. The complex has a center of inversion at the center of the parallelogram and Ci symmetry. In the crystal structure of 3, the cadmium atom with a CdN2O5 environment has a distorted capped trigonal prismatic geometry. Complex 4 also has a distorted square-pyramidal geometry (HgN2OCl2). In the networks of HEAC and the complexes 1–4, intermolecular hydrogen bonds form different types of hydrogen bond motifs between adjacent molecules.
    Polyhedron 01/2014; 67:27–35. DOI:10.1016/j.poly.2013.08.065 · 2.05 Impact Factor
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    ABSTRACT: An octadentate cyclen-based europium complex with amidic and hydroxyalkyl pendent moieties exhibits pH dependent ligand denticity associated with anion recognition. Unusually high hydration numbers are determined for ortho-phthalate ternary outer-sphere complexes for which modulation of lanthanide-based luminescence is observed.
    Chemical Communications 01/2014; 50(13). DOI:10.1039/c3cc48628a · 6.72 Impact Factor
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    ABSTRACT: In order to investigate possible isostructural solid solutions of disubstituted N-phenylformamides and thioamides, we have studied the re-crystallization of pairs of compounds selected from 2,6-difluoro-N-phenylformamide (I), 2,6-dichloro-Nphenylformamide (II), 2,6-dimethyl-N-phenylformamide (III), 2,6-dichloro-N-phenylthioamide (IV), 2,6-dimethyl-Nphenylthioamide (V), 2,6-diisopropyl-N-phenylformamide (VI) and 2,6-diisopropyl-N-phenylthioamide (VII). For single-component 2,6-disubstituted--phenylformamides only the trans form occurs in the pure crystal, while for thioamides the cis form occurs, with only one exception. By forming solid solutions of pairs of these molecules the resulting structures all adopt similar N—H� � �O/S chains in the crystals. Solid solutions (1), (2) and (3), resulting from the mixing of (I) and (II), (II) and (III), and (IV) and (V), respectively, are all isostructural with each other (space group Pbca). Only cocrystal (1) is isostructural to both starting materials, while (2) is isostructural to only one of the starting pair, (II). Solid solution (3), which adopts the same Pbca structure as (1) and (2), is different to the monoclinic structures of both the reactants. Solid solution (4) is monoclinic, with similar hydrogen-bonded chains, and isostructural to the two components, resulting from the composition from the mixing of (VI) and (VII). Isostructural indices were used to quantify crystal-packing similarities and differences. Occupancy factors of the reactants in each co-crystal differ widely.
    Acta Crystallographica Section B 01/2014; B70:106-114.
  • Sanaz Khorasani, Manuel A. Fernandes
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    ABSTRACT: Electron donor-to-acceptor interactions between 9-methylanthracene and bis(N-cyclobutylimino)-1,4-dithiin lead to the formation of chiral charge-transfer (CT) crystals. The structure consists of charge-transfer stacks where these two molecules arrange in a 1:1 alternating arrangement. These undergo a topochemical thermal single-crystal-to-single-crystal (SCSC) [2 + 4] Diels–Alder reaction in the solid state. CT crystals were reacted at 40 °C, their structures were determined by X-ray diffraction at various degrees of conversion, and they were examined using Hirshfeld surfaces and lattice energy calculations to find evidence of reaction cooperativity and feedback mechanisms. The results show that steric effects between product molecules and reactant molecules during the SCSC reaction influence the formation of products along the b axis, resulting in a more ordered structure than initially suggested by the crystal structure analysis. A maximum reaction conversion of around 96% was obtained, which indicates that the reaction is also nonrandom within the charge-transfer stacks. Lattice and intramolecular energy calculations show that the energy of an inherently metastable crystal obtained via the SCSC reaction is slightly higher compared to that of the recrystallized product crystal. Finally, structural analysis using CrystalExplorer shows that the shape, size, and surface curvature of the Hirshfeld surface are not much changed by the reaction, indicating that the reaction cavity remains relatively constant and that the reaction is under topochemical control.
    Crystal Growth & Design 11/2013; 13(12):5499–5505. DOI:10.1021/cg401474f · 4.56 Impact Factor
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    ABSTRACT: Preliminary results towards the synthesis of a corrole-based vitamin B12 analogue are reported. The synthesis of three simple corroles, 5,10,15-triphenylcorrole (TPCrl), 5,10,15-tri(2-nitrophenyl)corrole and 10-(4-methoxyphenyl)-5,15-diphenylcorrole is described. The synthesis of 10-[2-(benzoylamino)phenyl]-5,15-diphenylcorrole (DPAPCrl) suggests that a large, bulky meso substituent can be incorporated into the corrole with no loss of stability or significant decrease in yield. Both TPCrl and DPAPCrl were crystallized and their crystal structure is reported.
    South African journal of chemistry. Suid-Afrikaanse tydskrif vir chemie 08/2013; 66. · 0.53 Impact Factor
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    ABSTRACT: In this work, we identify and describe a moiety that may be capable of encouraging the formation of polymorphs. Four new N-phenylbenzamide-based compounds have been synthesized yielding four pairs of polymorphs upon recrystallization. The structures of these have been discussed and compared with the previously reported polymorphs of N-[2-(hydroxymethyl)phenyl]benzamide. The results indicate that the conformation of the N-phenylbenzamide group is generally constant but is sometimes altered by the crystal packing. The N-phenylbenzamide group is capable of intermolecular N–H···O hydrogen bonding but requires a change in conformation which is generally resisted by the molecule. As a consequence, weak forces such as C–H···O, C–H···N, C–H···π, and π···π interactions play significant but varying roles in these structures. One possible reason for the varying nature of the π···π interactions may be due to the variation of the electrostatic potential across the N-phenylbenzamide group in which negative and positive regions alternate across the face of the molecule. It is the combination of all these attributes that possibly leads to polymorphism being observed in the structures reported here.
    Crystal Growth & Design 07/2013; 13(8):3463–3474. DOI:10.1021/cg400356s · 4.56 Impact Factor
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    ABSTRACT: Cob(i)alamin reacts with phenylacetylene to produce two diastereomers in which the organic ligand is coordinated to the upper (β) and lower (α) face of the corrin ring, respectively. The isomers were separated chromatographically and characterised by ESI-MS and, in the case of the β isomer, by (1)H and (13)C NMR. Only the β isomer crystallised and its molecular structure, determined by X-ray diffraction, shows that the organic ligand coordinates Co(iii) through the β carbon of the phenylvinyl ligand. The Co-C bond length is 2.004(8) Å while the Co-N bond length to the trans 5,6-dimethylbenzimidazole (dmbzm) base is 2.217(8) Å, one of the longest Co-Ndmbzm bond lengths known in an organocobalamin. Unlike benzylcobalamin (BzCbl), phenylvinylcobalamin (PhVnCbl) is stable towards homolysis. DFT calculations (BP86/TZVP) on model compounds of BzCbl and PhVnCbl show that the Co-C bond dissociation energy for homolysis to Co(ii) and an organic radical in the former is 8 kcal mol(-1) lower than in the latter. An analysis of the electron density at the Co-C bond critical point using Bader's QTAIM approach shows that the Co-C bond in PhVnCbl is shorter, stronger and somewhat more covalent than that in BzCbl, and has some multiple bond character. Together with calculations that show that the benzyl radical is more stable than the phenylvinyl radical, this rationalises the stability of PhVnCbl compared to BzCbl. The phenylvinyl ligand has a large trans influence. The pKa for deprotonation of dmbzm and its coordination by the metal in β-PhVnCbl is 4.60 ± 0.01, one of the highest values reported to date in cobalamin chemistry. The displacement of dmbzm ligand by CN(-) in β-PhVnCbl occurs with log K = 0.7 ± 0.1; the trans influence order of C-donor ligands is therefore CN(-) < CCH < CHCH2 = PhVn < Me < Et.
    Dalton Transactions 03/2013; 42(21). DOI:10.1039/c3dt50336d · 4.10 Impact Factor
  • Richard M. Mampa, Manuel A. Fernandes, Laurence Carlton
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    ABSTRACT: The complexes [(dppp)Pt{(μ-C2C5H4N)W(CO)4(PR3)}2] (dppp = Ph2P(CH2)3PPh2; PR3 = PPh3 (1), P(4-XC6H4)3 (X = Me (2), OMe (3), F (4)) P(NMe2)3 (5)) were prepared from [(dppp)Pt(C2C5H4N)2] and cis-[W(CO)4(PR3)(CH3CN)] and were characterized by 1H, 13C, 15N, 31P, 183W and 195Pt NMR spectroscopy. The complex [(Ph3P)2Rh(H)2(μ-PTC)W(CO)4(P(4-MeC6H4)3)] (6) was prepared similarly, from [(Ph3P)2Rh(H)2(PTC)] (thiazole nitrogen and carboxylate oxygen attached to the metal) and cis-[W(CO)4(P(4-MeC6H4)3)(CH3CN)] and was characterized by NMR (1H, 13C, 15N, 31P, 103Rh and 183W) and by X-ray crystallography, which shows π–π interactions between the bridging pyridyl and a phenyl group from a phosphine on each metal. In complexes 1–5, there is little variation in the platinum chemical shift, indicating that electronic influences through the pyridylacetylide bridge are minimal. Graphical Abstract A bimetallic complex of rhodium and tungsten bridged by 2-(4-pyridyl)-thiazole-4-carboxylate is reported together with an NMR spectroscopic study of a series of trinuclear complexes of platinum and tungsten bridged by 4-pyridylacetylide.
    Transition Metal Chemistry 03/2013; 38(2). DOI:10.1007/s11243-012-9681-5 · 1.40 Impact Factor
  • Laurence Carlton, Lebohang V Mokoena, Manuel A Fernandes
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    ABSTRACT: Tungsten-183 NMR data are reported for the complexes cis-[W(CO)(4) (PPh(3) )(4-RC(5) H(4) N)] (R = H, Me, Ph, COMe, COPh, OMe, NMe(2) , Cl, NO(2) ). The (183) W chemical shift (obtained by indirect detection using (31) P) is found to correlate with the Hammett σ function for the group R, with (183) W shielding increasing approximately linearly with the donor strength of the pyridine over a range of 93 ppm. The X-ray structures of cis-[W(CO)(4) (PPh(3) )(4-MeOC(5) H(4) N)] and cis-[W(CO)(4) (PPh(3) )(4-PhCOC(5) H(4) N)] are also reported. Copyright © 2013 John Wiley & Sons, Ltd.
    Magnetic Resonance in Chemistry 02/2013; 51(4). DOI:10.1002/mrc.3925 · 1.56 Impact Factor
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    ABSTRACT: The title indole derivative, C(17)H(15)NO(3)S, crystallizes with two independent mol-ecules in the asymmetric unit. The benzene ring of the tosyl group is almost perpedicular to the indole ring in both mol-ecules, with inter-planar angles of 82.60 (5)° and 81.82 (6)°. The two mol-ecules are, as a consequence, able to form an almost centrosymmetric non-bonded dimer, in which the molecules are linked by pairs of C-H⋯π inter-actions. The crystal structure displays a three-dimensional network of C-H⋯O inter-actions. A π-π inter-action occurs between inversion-related indole rings with a centroid-centroid distance of 3.6774 (16) Å and an inter-planar angle of 1.53 (15)°. This inter-action leads to a stacking of mol-ecules along the a axis.
    Acta Crystallographica Section E Structure Reports Online 02/2013; 69(Pt 2):o219. DOI:10.1107/S160053681205180X · 0.35 Impact Factor
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    ABSTRACT: The HIV protease plays a major role in the life cycle of the virus and has long been a target in antiviral therapy. Resistance of HIV protease to protease inhibitors (PIs) is problematic for the effective treatment of HIV infection. The South African HIV-1 subtype C protease (C-SA PR), which contains eight polymorphisms relative to the consensus HIV-1 subtype B protease, was expressed in Escherichia coli, purified, and crystallized. The crystal structure of the C-SA PR was resolved at 2.7 Å, which is the first crystal structure of a HIV-1 subtype C protease that predominates in Africa. Structural analyses of the C-SA PR in comparison to HIV-1 subtype B proteases indicated that polymorphisms at position 36 of the homodimeric HIV-1 protease may impact on the stability of the hinge region of the protease, and hence the dynamics of the flap region. Molecular dynamics simulations showed that the flap region of the C-SA PR displays a wider range of movements over time as compared to the subtype B proteases. Reduced stability in the hinge region resulting from the absent E35-R57 salt bridge in the C-SA PR, most likely contributes to the increased flexibility of the flaps which may be associated with reduced susceptibility to PIs. An animated interactive 3D complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:36.
    Journal of biomolecular Structure & Dynamics 11/2012; 31(12). DOI:10.1080/07391102.2012.736774 · 2.98 Impact Factor
  • Sanaz Khorasani, Manuel A. Fernandes, Christopher B. Perry
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    ABSTRACT: Conformational flexibility in molecules plays a key role in many chemical and biological processes. It is a common belief that the larger the cycloalkane the more flexible it will be, and the more conformations it will adopt. While theoretical studies have shown that cyclododecane has many possible conformations, they have also consistently shown that one conformation is slightly more stable. In this work, we examine the effect of substitution and crystal packing on the conformation of singly substituted cyclododecane rings. This has been done by exploiting polymorphism in an attempt to induce new conformations in a specific molecule, as well as by examining structures reported in the Cambridge Structural Database (CSD). To this end, three polymorphs of N,N′-biscyclododecyl pyromellitic diimide (PMDI-12) have been identified and their structures elucidated. To rationalize the differences between the various polymorphs, molecule···molecule interaction energies have been calculated using atom–atom potential methods. Though the conformation of the PMDI-12 molecules as a whole may differ, examination of the conformation of the 12-membered ring indicates that it is conformationally identical in all three polymorphs. Examination of 20 other organic and organometallic structures containing this group in the CSD, indicates that they have the same conformation (only one possible exception in the 34 rings examined in this work), which suggests that the 12-membered ring adopts a single conformation ([3333] with D2 symmetry) in the solid-state that is relatively unaffected by crystal packing.
    Crystal Growth & Design 11/2012; 12(12):5908–5916. DOI:10.1021/cg300765b · 4.56 Impact Factor
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    ABSTRACT: The title macrocyclic amino alcohol compound, C14H30N4O, is investigated as a solid-state synthon for the design of a self-assembled tubular structure. It crystallizes in a helical column constructed by stereospecific O—H- - - -N and N—H- - - -N interactions. The hydrogen-bonding interactions, dependent upon macrocyclic ring helicity and molecular conformation, link R,R and S,S enantiomers in a head-to-tail fashion, forming a continuous hydrophilic inner core.

Publication Stats

673 Citations
301.67 Total Impact Points

Institutions

  • 2001–2015
    • University of the Witwatersrand
      • School of Chemistry
      Johannesburg, Gauteng, South Africa
  • 2012
    • University of KwaZulu-Natal
      • Department of Chemistry
      Port Natal, KwaZulu-Natal, South Africa
    • Rhodes University
      • Department of Chemistry
      Grahamstad, Eastern Cape, South Africa
  • 2007
    • University of Cologne
      • Institute of Organic Chemistry
      Köln, North Rhine-Westphalia, Germany