Mino R. Caira

University of Cape Town, Kaapstad, Western Cape, South Africa

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Publications (247)456.94 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the study was to generate alternative solid forms of 2-methoxyestradiol (2ME) and its sulfamoylated derivative 2-methoxyestradiol-3,17-O,O-bis-sulfamate (2MES), both of which are potent anticancer agents with no significant history of solid-state investigation. Screening for polymorphs and solvates by a variety of procedures yielded four distinct species: a crystalline form of 2ME, an amorphous form of 2ME, a chloroform solvate 2ME·(CHCl3 )2 , and the hemihydrate of the bis-sulfamate, 2MES·(H2 O)0.5 . Hydrogen-bonded assembly of 2ME molecules into layers in both crystalline 2ME and its chloroform solvate was established using single-crystal X-ray diffraction. This technique also revealed disorder of the sulfamate group at position 17 in both molecules comprising the asymmetric unit in the crystal of 2MES·(H2 O)0.5 . The thermal stabilities of the crystalline phases were recorded using hot-stage microscopy, thermogravimetry, and differential scanning calorimetry, and the results were reconciled with the crystal structures. Aqueous dissolution rates measured at 37°C generally decreased in the order 2MES·(H2 O)0.5 > 2ME(amorphous) > 2ME(crystalline). © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.
    Journal of Pharmaceutical Sciences 06/2015; DOI:10.1002/jps.24545 · 3.01 Impact Factor
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    ABSTRACT: The three possible structural isomers of 4-(pyridyl)pyrimidine were employed for the synthesis of new pyrrolo[1,2-c]pyrimidines and new indolizines, by 1,3-dipolar cycloaddition reaction of their corresponding N-ylides generated in situ from their corresponding cycloimmonium bromides. In the case of 4-(3-pyridyl)pyrimidine and 4-(4-pyridyl)pyrimidine the quaternization reactions occur as expected at the pyridine nitrogen atom leading to pyridinium bromides and consequently to new indolizines via the corresponding pyridinium N-ylides. However, in the case of 4-(2-pyridyl)pyrimidine the steric hindrance directs the reaction to the pyrimidinium N-ylides and, subsequently, to the formation of the pyrrolo[1,2-c]pyrimidines. The new pyrrolo[1,2-c]pyrimidines and the new indolizines were structurally characterized through NMR spectroscopy. The X-ray structures of two of the starting materials, 4-(2-pyridyl)pyrimidine and 4-(4-pyridyl)pyrimidine, are also reported.
    Beilstein Journal of Organic Chemistry 01/2015; 11:1079-1088. · 2.80 Impact Factor
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    ABSTRACT: The phytoalexin trans-resveratrol, 5-[(1E)-2-(4-hydroxyphenyl)ethenyl]-1,3-benzenediol, is a well-known, potent antioxidant having a variety of possible biomedical applications. However, its adverse physicochemical properties (low stability, poor aqueous solubility) limit such applications and its inclusion in cyclodextrins (CDs) has potential for addressing these shortcomings. Here, various methods of the attempted synthesis of inclusion complexes between trans-resveratrol and three methylated cyclodextrins (permethylated α-CD, permethylated β-CD and 2,6-dimethylated β-CD) are described. Isolation of the corresponding crystalline 1:1 inclusion compounds enabled their full structure determination by X-ray analysis for the first time, revealing a variety of guest inclusion modes and unique supramolecular crystal packing motifs. The three crystalline inclusion complexes were also fully characterized by thermal analysis (hot stage microscopy, thermogravimetric analysis and differential scanning calorimetry). To complement the solid-state data, phase-solubility studies were conducted using a series of CDs (native and variously derivatised) to establish their effect on the aqueous solubility of trans-resveratrol and to estimate association constants for complex formation.
    Beilstein Journal of Organic Chemistry 12/2014; 10:3136-51. DOI:10.3762/bjoc.10.331 · 2.80 Impact Factor
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    ABSTRACT: 7,8,9,10-Tetrahydropyrrolo[2,1-a]isoquinolines were obtained by 1,3-dipolar cycloaddition reactions of their corresponding N-ylides with olefinic (acrylonitrile) and symmetrical or non-symmetrical acetylenic dipolarophiles (methyl/ethyl propiolate, dimethyl acetylenedicarboxylate). Also, stable 5,6,7,8-tetrahydroisoquinolinium dicyanomethylide was isolated and characterized by X-ray diffraction analysis.
    Tetrahedron Letters 10/2014; 55(41):5635–5638. · 2.39 Impact Factor
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    ABSTRACT: (+)-(2R,3R)-1,1,4,4-Tetraphenylbutane-1,2,3,4-tetraol (TETROL) functions as a highly efficient host for the inclusion of cyclohexanone and 2-, 3- and 4-methylcyclohexanone, all with 1:1 host:guest ratios. Most extraordinarily, the 3- and 4-methyl isomers are uniquely included in their higher energy axial methyl conformations rather than as their more energetically favorable equatorial analogues. In contrast, 2-methylcyclohexanone is included more conventionally in the equatorial methyl conformation. During recrystallization of TETROL from racemic 2- and 3-methylcyclohexanone, some preference is shown by the host for the (R)-enantiomer. In the latter case, this is attributed to a much stronger H-bond between a hydroxyl group of TETROL and the carbonyl group of the (R)-enantiomer (O...O 2.621(2) angstroms) compared with a significantly weaker H-bond to the (S)-enantiomer (3.125(8) angrstroms). In the former instance, hydrogen bond strengths to both enantiomers are similar but the (R)-enantiomer engages in three (guest)CH...pi(host) and three (guest)H...Car(host) contacts while fewer interactions of these types are observed for the (S)-enantiomer. Calculations of geometries of the guest cyclohexanones were determined at the MP2/6-311++G(2df,2p) level and compared with those obtained at the G3(MP2) level. Finally, an interesting correlation between crystal packing indices for the three methylcyclohexanone clathrates and their respective desolvation onset temperatures was identified.
    Chemical Communications 09/2014; 50:13353-13355. DOI:10.1039/c4cc06826b · 6.72 Impact Factor
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    ABSTRACT: 7,8,9,10-Tetrahydropyrrolo[2,1-a]isoquinolines were obtained by 1,3-dipolar cycloaddition reactions of their corresponding N-ylides with olefinic (acrylonitrile) and symmetrical or non-symmetrical acetylenic dipolarophiles (methyl/ethyl propiolate, dimethyl acetylenedicarboxylate). Also, stable 5,6,7,8-tetrahydroisoquinolinium dicyanomethylide was isolated and characterized by X-ray diffraction analysis.
    Tetrahedron Letters 09/2014; 55(41):5635–5638. DOI:10.1016/j.tetlet.2014.08.054 · 2.39 Impact Factor
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    ABSTRACT: 3-(6-Methoxypyridin-3-yl)-5-(4-methylsulfonyl phenyl)-pyridin-2-amine (MMP) is a member of a novel class of orally active antimalarial drugs. This aminopyridine molecule has shown potent in vitro antiplasmodial activity and in vivo antimalarial activity in Plasmodium berghei-infected mice. The aqueous solubility of this molecule is, however, limited. Thus investigations aimed at improving the physicochemical properties, including solubility, of MMP were accordingly conducted. Five salts of MMP were formed with co-former molecules saccharin, salicylic acid, fumaric acid, oxalic acid and suberic acid, but a cocrystal was obtained when the co-former adipic acid was employed. All these new multicomponent systems have been fully characterised using X-ray diffraction and thermal methods. Semiquantitative, turbidimetric solubility tests in a phosphate-buffered saline solution at a pH of 7.4 were performed on the salts and the cocrystal of MMP. The saccharinate salt, fumarate salt and the cocrystal of MMP proved to have greater solubility than MMP itself. This work illustrates the importance of screening and modifying candidate drug compounds in their preliminary stages of development.
    CrystEngComm 06/2014; 2014(16):5781-5792. DOI:10.1039/C3CE41798K · 3.86 Impact Factor
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    ABSTRACT: In this article we present a detailed structural investigation of novel polycyclic pentacyclo[5.4.1.0(2,6).0(3,10).0(5,9)]undecane and adamantane propargylamine hybrid molecules. The structural characterization of these compounds was performed using MS, FT-IR and NMR spectroscopy in combination with X-ray diffraction analysis. The single crystal X-ray analyses of four synthons (6, 8-10) are presented; 8-(N)-propargylamino-8,11-oxapentacyclo-[5.4.1.0(2,6).0(3,10).0(5.9)]undecane (compound 6 crystallized in the monoclinic system, unit cell parameters: a = 20.737(2) angstrom; b = 8.127(1) angstrom; c = 12.606 (1) ; beta = 92.360(2)degrees; V = 2122.8(3) angstrom(3); Z = 8); 11-hydroxy-(N)-propargyl-8,11-azapentacyclo[5.4.1.0(2,6).0(3,10).0(5.9)]undecane (compound 8 crystallized in the monoclinic system, unit cell parameters: a = 7.9624(6) angstrom; b = 14.9332(6) angstrom; c = 9.6162(7) angstrom; beta = 109.029(3); V = 1080.9(2) angstrom(3); Z = 4); 1-methyl-11-hydroxy-(N)-propargyl-8,11-azapentacyclo[5.4.1.0(2,6).0(3,10).0(5.9)]undecane (compound 9 crystallized in the monoclinic system, unit cell parameters: a = 7.732(1) angstrom; b = 15.148(2) angstrom; c = 9.864(1) ; beta = 101.728(3)angstrom; V = 1131.3 (2) angstrom(3); Z = 4); and an adamantane derivative, N,N-dipropargyl-adamantan-1-amine (compound 10 crystallized in the orthorhombic system, unit cell parameters: a = 34.098(4) angstrom; b = 6.825(1) angstrom; c = 10.979(1) angstrom; V = 2555.0(5) angstrom(3); Z = 8). From the X-ray analyses it is clear that the polycyclic structures had different modes of intermolecular interaction and molecular stacking. Compound 9 exhibited a cis configuration between the OH and CH3 moieties as expected in view of potential steric hindrance and the electron density effects of the methyl moiety on the initial amination reaction. These hybrid molecules exhibited significant anti-apoptotic activity and could thus find application as neuroprotective agents.
    Journal of Chemical Crystallography 04/2014; 44(4). DOI:10.1007/s10870-014-0501-y · 0.48 Impact Factor
  • Susan A. Bourne, Mino R. Caira
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    ABSTRACT: 1.Introduction2.General Classification and Description2.1.Inorganic Hosts and Their Inclusion Compounds2.2.Applications of Inorganic Systems2.3.Organic Hosts and Their Inclusion Compounds2.4.Applications of Organic Systems3.Methods of Characterization
    Ullmann's Encyclopedia of Industrial Chemistry, 03/2014: pages 1-20; , ISBN: 9783527306732
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    ABSTRACT: 7,8,9,10-Tetrahydropyrrolo[2,1-a]isoquinolines were obtained by 1,3-dipolar cycloaddition reactions of their corresponding N-ylides with olefinic (acrylonitrile) and symmetrical or non-symmetrical acetylenic dipolarophiles (methyl/ethyl propiolate, dimethyl acetylenedicarboxylate). Also, stable 5,6,7,8-tetrahydroisoquinolinium dicyanomethylide was isolated and characterized by X-ray diffraction analysis.
    Tetrahedron Letters 01/2014; 55(41):5635–5638. · 2.39 Impact Factor
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    ABSTRACT: The identification and application of (+)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetrol (TETROL) as an efficient and selective host compound is described. Computational and single crystal X-ray diffraction analyses revealed that the butane backbone of TETROL adopts a relatively rigid anti-conformation, with the hydroxy groups oriented syn and connected through a cyclic, homodromic arrangement of their O-H bonds. This structure is stabilised through a pair of 1,3-hydrogen bonding interactions. TETROL forms inclusion complexes with pyridine and 3- and 4-methylpyridine, and does so selectively from mixtures of the pyridines. X-ray diffraction (single crystal and powder) and thermal analyses of the inclusion compounds are described.
    Tetrahedron 10/2013; 69(41):8713. DOI:10.1016/j.tet.2013.07.094 · 2.82 Impact Factor
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    ABSTRACT: Screening for new solid forms of the antihypertensive lisinopril was performed by recrystallization of the commercial form, lisinopril dihydrate, from various solvents and by exposing the product of its dehydration to a series of vapors under controlled conditions. Modifications other than the dihydrate encountered in the study included new anhydrous and amorphous forms, with intrinsic dissolution rates significantly greater than that of the dihydrate. Further physicochemical characterization included constant and programmed temperature powder X-ray diffraction, differential scanning calorimetry, thermogravimetry, and Fourier transform infrared spectroscopy. In the course of this study, the single-crystal X-ray structure of lisinopril dihydrate, [a = 14.550(2), b = 5.8917(8), c = 14.238(2) Å, β = 112.832(3)° at T = 173(2) K, space group P21 , Z = 2], was determined for the first time, revealing its double zwitterionic character in the solid state. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 10/2013; 102(10). DOI:10.1002/jps.23660 · 3.01 Impact Factor
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    ABSTRACT: The new chiral bis(arsine) ligand N,N'-bis[2'(diphenylarsino)benzoyl]-(1R,2R)-cyclohexanediamine (BiAsBA, 3), based on the backbone of the Trost modular ligand (TML), was synthesized in three steps. A useful approach to introduce the -AsPh2 group on arsine ligands by Pd-catalyzed arsination was used. The molecular structure and configuration of the BiAsBA ligand was determined by single-crystal X-ray crystallography. In the asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate very high to complete conversion and modest enantioselectivity were achieved. Despite the low enantioselectivity obtained, the bis(arsine) ligand BiAsBA showed significant potential, since it provided a higher ee value than the phosphorus-containing homologous "Trost standard ligand" (TSL) with the same substrate.
    Organometallics 06/2013; 32(11):3220-3226. DOI:10.1021/om400144s · 4.25 Impact Factor
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    ABSTRACT: The interaction in the solid state between ciprofloxacin (CIP) and norfloxacin (NOR) was investigated and a new multicomponent molecular complex (COP) was obtained and characterized. It is composed of equimolar quantities of both compounds, according to TLC and 1H NMR data. As single-crystal X-ray analysis showed, COP crystallizes in the triclinic system, space group P(1̅). The asymmetric unit comprises three independent zwitterions (A, B, and C) with contributions of both CIP and NOR, as well as 14.6 water molecules. At the zwitterion A site, the occurrence is about 37% (CIP), 63% (NOR); at the B site, there is predominantly CIP (70%); and at the C site the occurrence is about 43% (CIP) and 57% (NOR), yielding an overall 1:1 CIP-NOR ratio in the crystal. TG data evidenced a one-step loss of solvent (about 18% per COP zwitterion) below 110 °C, confirming the presence of water molecules. The propensity for heteroassociation between CIP and NOR, under the conditions described herein, originated a co-crystal reported for the first time between FQs, and became one of the most interesting aspects of this research.
    Crystal Growth & Design 03/2013; 13(3). DOI:10.1021/cg301299e · 4.56 Impact Factor
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    ABSTRACT: Tizoxanide [2-(hydroxy)-N-(5-nitro-2-thiazolyl)benzamide, TIZ] is a new potent anti-infective agent which may enhance current therapies for leishmaniasis, Chagas disease and viral hepatitis. The aim of this study was to identify the conformational preferences that may be related to the biological activity of TIZ by resolving its crystal structure and characterizing various physicochemical properties, including its experimental vibrational and 13C nuclear magnetic resonance properties, behavior on heating and solubility in several solvents at 25 °C. TIZ crystallizes from dimethylformamide as the carboxamide tautomer in the triclinic system, space group P(−1) (No. 2) with the following unit cell parameters at 173(2) K: a = 5.4110(3) Å, b = 7.3315(6) Å, c = 13.5293(9) Å, α = 97.528(3), β = 95.390(4), γ = 97.316(5), V = 524.41(6) Å3, Z = 2, Dc = 1.680 g/cm3, R1 = 0.0482 and wR2 = 0.0911 for 2374 reflections. This modification of TIZ has a ‘graphitic’ structure and is composed of tightly packed layers of extensively hydrogen-bonded molecules. The various spectroscopic data [Diffuse Fourier transform infrared (DRIFT) and FT-Raman, recorded in the range 3600–500 and 4000–200 cm−1 respectively, and solid-state 13C NMR] were consistent with the structure determined by X-ray crystallography. From DSC, TG and thermomicroscopy, it was concluded that TIZ is thermally stable as a solid and that melting is not an isolated event from the one-step thermal decomposition that it undergoes above 270 °C. This modification of TIZ is practically insoluble in water and slightly soluble in polar aprotic solvents such as dimethylsulfoxide, dimethylformamide and dioxane.
    Journal of Molecular Structure 03/2013; 1036:318–325. DOI:10.1016/j.molstruc.2012.12.004 · 1.60 Impact Factor
  • Mino R. Caira
    ChemInform 02/2013; 44(8). DOI:10.1002/chin.201308247
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    ABSTRACT: A series of oligomeric lactones, namely tetra- and hexasalicylides 1 and 2, was synthesized from various halogenated salicylic acids by a cyclocondensation reaction using POCl3. The clathrate inclusion properties of the macrocycles for some organic solvents were investigated. X-ray structures of several representative clathrates in this series were determined and the results were used to explain various features of their thermal desolvation. Halogen bonding (in particular C–I⋯OC) was found to play a significant role in the thermal stabilization of these crystalline clathrates.
    Tetrahedron 01/2013; 69(3):1120–1127. DOI:10.1016/j.tet.2012.11.057 · 2.82 Impact Factor
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    ABSTRACT: Naphthoquinones have been found to have a wide range of biological activities, including cytotoxicity to cancer cells. The secondary metabolites lapachol, α- and β-lapachone and a series of 25 related synthetic 1,4-naphthoquinones were screened against the oesophageal cancer cell line (WHCO1). Most of the compounds exhibited enhanced cytotoxicity (IC(50) 1.6-11.7 μM) compared to the current drug of choice cisplatin (IC(50) = 16.5 μM). This study also established that the two new synthetic halogenated compounds 12a and 16a (IC(50) = 3.0 and 7.3 μM) and the previously reported compound 11a (IC(50) = 3.9 μM), were non-toxic to NIH3T3 normal fibroblast cells. Cell death of oesophageal cancer cells by processes involving PARP cleavage caused by 11a was shown to be associated with elevated c-Jun levels, suggesting a role for this pathway in the mechanism of action of this cohort of naphthoquinone compounds.
    European Journal of Medicinal Chemistry 01/2013; 62C:98-110. DOI:10.1016/j.ejmech.2012.12.048 · 3.43 Impact Factor
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    ABSTRACT: The hydrolysis reaction of fenitrothion was studied in water containing 2% dioxane and in the presence of native cyclodextrins (α-, β- and γ-CD) and two commercially available modified derivatives, namely, permethylated β- and α-cyclodextrin (TRIMEB and TRIMEA, respectively). The kinetics of the reaction in the presence of TRIMEA could not be measured because the complex formed is insoluble and precipitated even at low concentration. On the other hand, the reaction is only weakly affected by the presence of α-CD. The hydrolysis reaction is inhibited by all the other cyclodextrins. From the kinetic data the association equilibrium constants for the formation of the 1:1 inclusion complexes were determined as 417, 511 and 99M−1 for β-CD, TRIMEB and γ-CD, respectively. Despite the differences in the association constants for β- and γ-CD, the observed inhibition effect is about the same and this is due to the fact that the rate of hydrolysis in the cavity of γ-CD is smaller than that in the cavity of β-CD. The strongest inhibitor is TRIMEB and this result is consistent with the known structure of the complex in the solid state.

Publication Stats

2k Citations
456.94 Total Impact Points

Institutions

  • 1972–2015
    • University of Cape Town
      • Department of Chemistry
      Kaapstad, Western Cape, South Africa
  • 2007–2011
    • Rhodes University
      • Department of Chemistry
      Grahamstad, Eastern Cape, South Africa
  • 2005
    • University of Louisiana at Monroe
      • Department of Basic Pharmaceutical Sciences
      Monroe, LA, United States
    • Port Elizabeth Museum
      Port Elizabeth, Eastern Cape, South Africa
  • 2004
    • Academia Romana
      • Department of Organic Chemistry
      Bucureşti, Hunedoara, Romania
  • 2000
    • Okayama University
      • Faculty of Science
      Okayama, Okayama, Japan