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Simon Parsons

Publications and source records attributed to Simon Parsons.

At least 91 records · Page 5Linked to original sources
PubMed2004

Structures of piperazine, piperidine and morpholine.

The crystal structures of piperazine, piperidine and morpholine have been determined at 150 K. All three structures are characterized by the formation of NH...N hydrogen-bonded chains. In piperazine these are linked to form sheets, but the chains are shifted so that the molecules interleave. In morpholine there are in addition weak CH...O interactions. Topological analyses show that these three structures are closely related to that of cyclohexane-II, which can be described in terms of a pseudo-cubic close-packed array of molecules in a familiar ABC layered arrangement. While the positions of the molecules within each layer are similar, hydrogen bonding occurs between the ABC layers and in order to accommodate this the molecules are rotated relative to those in cyclohexane-II. Piperidine and morpholine also adopt layered structures, with hydrogen-bonding or CH...O interactions between the layers. In these cases, however, the layering more resembles a hexagonal close-packed arrangement.

Journal Article↗
PubMed2004

Isomeric eremophilane lactones from Senecio tsoongianus.

From the whole plant of Senecio tsoongianus, two pairs of epimers, tsoongianolides A (1) and B (2), and tsoongianolides C (3) and D (4), and two new sesquiterpene lactones, tsoongianolides E (5) and F (6), all of which possess the eremophilane skeleton, were isolated. Two known eremophilane dimers (7) and (8) were also obtained from this species. Their absolute structures were elucidated by 1D- and 2D-NMR techniques and by X-ray diffraction studies, along with chemical evidence.

Isomerism↗
PubMed2004

Configurations of metallocyclams and relevance to anti-HIV activity.

Antiviral cyclam macrocycles block viral entry into cells by binding to the CXCR4 co-receptor. Cyclams bind transition metal ions strongly and can potentially form a range of trans (I-V) and cis configurations which may be recognised differently by co-receptor proteins. A survey of the CSD (crystallographic structural database) shows that the trans-III configuration is the most common in the solid state for complexes of cyclam itself. Other configurations can be induced by N-substitution or ternary complexation and by interaction with solvents in solution. We report X-ray structures for the square-planar trans-III complexes [Pd(cyclam)]Cl(2).2MeOH and the C-C linked dimer [Pd(2)(2,2'-bi-(1,4,8,11-tetraazacyclotetradecane))](ClO4)(4), in which the planes of the two cyclam rings are close to perpendicular (100.1 degrees ), and for tetra-N-benzyl-cyclam and its 5-coordinate Ni(II) complex [Ni(Bz(4)-cyclam)Cl]Cl which has the unusual trans-I configuration.

Anti-HIV Agents↗
PubMed2003

A chiral alkyltris(pyrazolyl)borate ligand: synthesis of [(Ipc)B(pz)3Mn(CO)3] and [(Ipc)B(pz)3Ru(p-cymene)]PF6 (Ipc = Isopinocampheyl).

The application of the reagent (Ipc)BCl(2) (Ipc = isopinocampheyl) in the synthesis of a new tris(pyrazolyl)borate ligand having an Ipc substituent on boron is described. The sodium salt is a convenient precursor for the preparation of the complexes [(Ipc)tris(pyrazolyl)borato]tricarbonylmanganese and [[(Ipc)tris(pyrazolyl)borato](p-cymene)ruthenium](+), whose X-ray crystal structures are reported. While little distortion of the B(pz)(3)M unit is observed in these complexes, steric interaction between the Ipc group and the 3-positions of the pyrazolyl rings is noted to lead to distortion of the angles around the B-C bond.

Journal Article↗
PubMed2003

Kinetics of aquation and anation of ruthenium(II) arene anticancer complexes, acidity and X-ray structures of aqua adducts.

The aqua adducts of the anticancer complexes [(eta(6)-X)Ru(en)Cl][PF(6)] (X=biphenyl (Bip) 1, X=5,8,9,10-tetrahydroanthracene (THA) 2, X=9,10-dihydroanthracene (DHA) 3; en=ethylenediamime) were separated by HPLC and characterised by mass spectrometry as the products of hydrolysis in water. The X-ray structures of the aqua complexes [(eta(6)-X)Ru(en)Y][PF(6)](n), X=Bip, Y=0.5 H(2)O/0.5 OH, n=1.5 (4), X=THA, Y=0.5 H(2)O/0.5 OH, n=1.5 (5 A), X=THA, Y=H(2)O, n=2 (5 B), and X=DHA, Y=H(2)O, n=2 (6), are reported. In complex 4 there is a large propeller twist of 45 degrees of the pendant phenyl ring with respect to the coordinated phenyl ring. Although the THA ligand in 5 A and 5 B is relatively flat, the DHA ring system in 6 is markedly bent (hinge bend ca. 35 degrees ) as in the chloro complex 3 (41 degrees ). The rates of aquation of 1-3 determined by UV/Vis spectroscopy at various ionic strengths and temperatures (1.23-2.59x10(-3) s(-1) at 298 K, I=0.1 M) are >20x faster than that of cisplatin. The reverse, anation reactions were very rapid on addition of 100 mM NaCl (a similar concentration to that in blood plasma). The aquation and anation reactions were about two times faster for the DHA and THA complexes compared to the biphenyl complex. The hydrolysis reactions appear to occur by an associative pathway. The pK(a) values of the aqua adducts were determined by (1)H NMR spectroscopy as 7.71 for 4, 8.01 for 5 and 7.89 for 6. At physiologically-relevant concentrations (0.5-5 microM) and temperature (310 K), the complexes will exist in blood plasma as >89 % chloro complex, whereas in the cell nucleus significant amounts (45-65 %) of the more reactive aqua adducts would be formed together with smaller amounts of the hydroxo complexes (9-25 %, pH 7.4, [Cl(-)]=4 mM).

Animals↗
PubMed2003

New lupane derived compounds with pro-apoptotic activity in cancer cells: synthesis and structure-activity relationships.

Cellular screening of various synthetic triterpenoid compounds formally derived from lupane has identified a number of analogues as potential anticancer drug candidates. Here we describe the synthesis and structure-activity relationships of betulin and betulinic acid derivatives containing an E-ring modified with different oxygen functions. Thus compounds containing the lup-18-en-21-one, lup-18-ene-21,22-dione, 18,19-secolupane, and the highly oxygenated 18,19-secolupane systems, as well as des-E-lupane derivatives, were prepared from the readily available natural pentacyclic triterpene betulin using oxidative procedures. These compounds were named betulinines. We demonstrate that only selected compounds, particularly those containing a lupane E-ring-derived unsaturated ketone or diketone function, possessed in vitro cytotoxic activity against tumor cell lines, suggesting a structure-activity relationship.

Animals↗
PubMed2003

Induced-fit recognition of DNA by organometallic complexes with dynamic stereogenic centers.

Organometallic chemistry offers novel concepts in structural diversity and molecular recognition that can be used in drug design. Here, we consider DNA recognition by eta 6-arene Ru(II) anticancer complexes by an induced-fit mechanism. The stereochemistry of the dinuclear complex [((eta 6-biphenyl)RuCl(en))2-(CH2)6]2 + (3, en = ethylenediamine) was elucidated by studies of the half unit [(eta 6-biphenyl)RuCl(Et-en)]+ (2, where Et-en is Et(H)NCH2CH2NH2). The structures of the separated RRu*RN* and SRu*RN* diastereomers of 2 were determined by x-ray crystallography; their slow interconversion in water (t(1/2) approximately 2 h, 298 K, pH 6.2) was observed by NMR spectroscopy. For 2 and 3 the RRu*RN* configurations are more stable than SRu*RN* (73:27). X-ray and NMR studies showed that reactions of 2 and 3 with 9-ethylguanine gave rise selectively to SRu*RN* diastereomers. Dynamic chiral recognition of guanine can lead to high diastereoselectivity of DNA binding. The dinuclear complex 3 induced a large unwinding (31 degrees) of plasmid DNA, twice that of mononuclear 2 (14 degrees), and effectively inhibited DNA-directed RNA synthesis in vitro. This dinuclear complex gave rise to interstrand cross-links on a 213-bp plasmid fragment with efficiency similar to bifunctional cisplatin, and to 1,3-GG interstrand and 1,2-GG and 1,3-GTG intrastrand cross-links on site-specifically ruthenated 20-mers. Complex 3 blocked intercalation of ethidium considerably more than mononuclear 2. The concept of induced-fit recognition of DNA by organometallic complexes containing dynamic stereogenic centers via dynamic epimerization, intercalation, and cross-linking may be useful in the design of anticancer drugs.

Antineoplastic Agents↗
PubMed2003

Zinc(II) complexes with intramolecular amide oxygen coordination as models of metalloamidases.

Polydentate ligands (6-R1-2-pyridylmethyl)-R2(R1= NHCOtBu, R2= bis(2-pyridylmethyl)amine L1, bis(2-(methylthio)ethyl)amine L2 and N(CH2CH2)2S L3) form mononuclear zinc(II) complexes with intramolecular amide oxygen coordination and a range of coordination environments. Thus, the reaction of Zn(ClO4)2.6H2O with L1-3 in acetonitrile affords [(L)Zn](ClO4)2(L=L1, 1; L2, 2) and [(L3)Zn(H2O)(NCCH3)](ClO4)2 3. The simultaneous amide/water binding in resembles the motif that has been proposed to be involved in the double substrate/nucleophile Lewis acidic activation and positioning mechanism of amide bond hydrolysis in metallopeptidases. X-ray diffraction, 1H and 13C NMR and IR data suggests that the strength of amide oxygen coordination follows the trend 1>2 >3. L1-3 and undergo cleavage of the tert-butylamide upon addition of Me4NOH.5H2O (1 equiv.) in methanol at 50(1)degrees C. The rate of amide cleavage follows the order 1> 2>> 3, L1-3. The extent by which the amide cleavage reaction is accelerated in 1-3 relative to the free ligands, L1-3, is correlated with the strength of amide oxygen binding and Lewis acidity of the zinc(II) centre in deduced from the X-ray, NMR and IR studies.

Amides↗
PubMed2003

Introduction to twinning.

A twinned crystal is an aggregate in which different domains are joined together according to a specific symmetry operation: the twin law. The diffraction patterns derived from different domains are rotated, reflected or inverted with respect to each other, depending on the nature of the relationship between the different domains, and weighted according to the quantity of a particular domain present in the crystal. The diffraction pattern measured during data collection is a superposition of all of these. Reflections from different domains may overlap and twinned crystals fall broadly into two categories in which either all reflections or only certain zones of reflections are affected by overlap. The former occurs when a crystal lattice belongs to a higher point group than the crystal structure itself; the latter frequently occurs when the twin law is a symmetry operation belonging to a higher symmetry supercell.

Crystallization↗
PubMed2003

Synthetic and structural studies of cobalt-pivalate complexes.

The synthesis and characterisation of a range of cobalt pivalate cage complexes are reported. The cages include: a dinuclear Co(II) complex; an oxo-centred Co(III) triangle; tetranuclear Co(II) heterocubanes and butterflies; tetranuclear heterovalent cobalt butterflies and hexanuclear edge-sharing bitetrahedra; heterovalent penta-, hexa- and hepta-nuclear cages based on [M(4)O(4)] heterocubane cores; and a tetradecanuclear cage based on heterocubanes sharing edges and vertices. Spectroscopic studies suggest that some of these cores are retained in solution, but that only in the Co(III) triangle is the structure including ligands retained. A scheme is proposed to account for the many structures observed, which may be applicable to other polymetallic cage complexes.

Journal Article↗
PubMed2003

Selective recognition of configurational substates of zinc cyclam by carboxylates: implications for the design and mechanism of action of anti-HIV agents.

The interaction of metal cyclams with carboxylate groups is thought to play an important role in their binding to the CXCR4 chemokine receptor and in their anti-HIV activity. Here we report the synthesis of acetate, phthalate, perchlorate and chloride complexes of Zn(II) cyclam (1,4,8,11-tetraazacyclotetradecane). The X-ray crystal structures of [Zn(cyclam)(phthalate)](n)(CH(3)OH)(2n) and [Zn(cyclam)(H(2)O)(2)](OAc)(2) contain octahedral Zn(II) centres. Phthalate acts as a bridging ligand in the former complex, binding through monodentate carboxylate groups, and giving rise to infinite chains in the lattice together with extensive hydrogen bonding between carboxylate donor oxygen atoms and amine and methanol acceptor atoms. The uncoordinated acetate groups and the aqua ligand in the acetate complex are also involved in a rich network of hydrogen bonds and this may account for the unusually long Zn[bond]O distance (2.27 A). In both crystalline complexes, the macrocycle adopts the trans-III (S,S,R,R) configuration. 1D (1)H NMR spectra of all four complexes have been fully assigned by a combination of 2D [(1)H, (1)H] COSY and TOCSY, and [(1)H, (13)C] and [(1 )H, (15)N] HSQC NMR data. In aqueous solution, the stable trans-III configuration found in the solid-state equilibrates slowly (hours at 298 K) with trans-I (R,S,R,S) and cis-V (R,R,R,R) configurations. The trans-III configuration is predominant in aqueous solution for both the chloride and perchlorate complexes, but for the acetate and phthalate complexes, the cis-V configuration dominates. Carboxylate groups appear to stabilize the cis-V configuration in solution through Zn(II) coordination and hydrogen bonding. Titration of the chloride Zn(II)-cyclam complex with acetate confirmed that carboxylates strongly induce formation of the cis-V configuration. This implies that carboxylates can exert a strong influence over configurational selectivity. Cyclam NH hydrogen bonding is prevalent both in the solid state and in solution, and is relevant to the anti-HIV activity of Zn(II) and other metal cyclam complexes and to their ability to recognize the CXCR4 transmembrane co-receptor.

Anti-HIV Agents↗
PubMed2003

The first structural characterisation of a group 2 metal alkylperoxide complex: comments on the cleavage of dioxygen by magnesium alkyl complexes.

A new high-yield synthesis of [(PhCH(2))(2)Mg(thf)(2)] and [[(PhCH(2))CH(3)Mg(thf)](2)] via benzylpotassium has allowed a simple entry into benzylmagnesium coordination chemistry. The syntheses and X-ray crystal structures of both [(eta(2)-Me(2)NCH(2)CH(2)NMe(2))Mg(CH(2)Ph)(2)] and [eta(2)-HC[C(CH(3))NAr'](2)Mg(CH(2)Ph)(thf)] (Ar'=2,6-diisopropylphenyl) are reported. The latter beta-diketiminate complex reacts with dioxygen to provide a 1:2 mixture of dimeric benzylperoxo and benzyloxo complexes. The benzylperoxo complex [[eta(2)-HC[C(CH(3))NAr'](2)Mg(mu-eta(2):eta(1)-OOCH(2)Ph)](2)] is the first example of a structurally characterised Group 2 metal-alkylperoxo complex and contains the benzylperoxo ligands in an unusual mu-eta(2):eta(1)-coordination mode, linking the two five-coordinate magnesium centres. The O[bond]O separation in the benzylperoxo ligands is 1.44(2) A. Reaction of the benzylperoxo/benzyloxo complex mixture with further [eta(2)-HC[C(CH(3))NAr'](2)Mg(CH(2)Ph)(thf)] results in complete conversion of the benzylperoxo species into the benzyloxo complex. This reaction, therefore, establishes the cleavage of dioxygen by this system as a two-step process that involves initial oxygen insertion into the Mg[bond]CH(2)Ph bond followed by O[bond]O/Mg[bond]C sigma-bond metathesis of the resulting benzylperoxo ligand with a second Mg[bond]CH(2)Ph bond. The formation of a 1:2 mixture of the benzylperoxo and benzyloxo species indicates that the rate of the insertion is faster than that of the metathesis, and this is shown to be consistent with a radical mechanism for the insertion process.

Journal Article↗