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Jeremy K M Sanders

Publications and source records attributed to Jeremy K M Sanders.

18 recordsLinked to original sources
PubMed2003

Selection and amplification of mixed-metal porphyrin cages from dynamic combinatorial libraries.

Mixed metallo-porphyrin cages were selected and amplified from dynamic combinatorial libraries (DCLs) by using appropriate templates. The cages are composed of two bisphosphine substituted zinc(II) porphyrins as ligand donors and two rhodium(III) or ruthenium(II) porphyrins as ligand acceptors, and are connected through metal-phosphorus coordination. Ru and Rh porphyrins that display a large structural diversity were employed. The templating was achieved by using 4,4'-bpy, 3,3'-dimethyl-4,4'-bipyridine and benzo[lmn]-3,8-phenanthroline, and acts through zinc-nitrogen coordination. The absolute amount of amplification from the DCLs is strongly dependent on the combination of the Ru/Rh porphyrin and the template; cages with sterically demanding porphyrins can only form with smaller templates. In the case of tert-butyl-substituted TPP (TPP=tetraphenylporphyrin), cages are not formed at all. The formation of the cages is usually complete within 24 h at an ambient temperature; in the case of the cage containing Rh(III)OEP (OEP=octaethylporphyrin) and bpy, the pseudo-first-order rate constant of cage formation was determined to be 2.1+/-0.1x10(-4) s(-1) (CDCl(3), 25 degrees C). Alternatively, heating the mixtures to 65 degrees C and cooling to room temperature yields the cages within minutes. The (1)H NMR chemical shifts of several characteristic protons show large differences upon changing the identity of the Ru/Rh porphyrin and the central metal; this is most likely to arise from variations in the geometry of the cages. The X-ray crystal structure of a cage, which contains Rh(III)OEP as a porphyrin acceptor and bpy as template, demonstrates that the cages can adopt severely distorted conformations to accommodate the relatively short templates. An extension to mixed DCLs showed that only limited selectivity is displayed by the various templates. Formation of mixed cages that contain two different rhodium porphyrins prevents effective selection, although the kinetic lability of the systems allows for some amplification. This lability, however, also prevents isolation of the individual cages. Removal of the template leads to re-equilibration, thus the templates act as scaffolds to keep the structures intact.

Journal Article↗
PubMed2003

Synthesis and characterization of carboxylate complexes of Sn(IV) porphyrin monomers and oligomers.

Most of the porphyrin-recognition chemistry we have investigated previously has centred on kinetically labile metal-ligand interactions, such as Z-N and Ru-N. Our interest in the broader scope of molecular recognition required a metal with the ability to specifically recognise non-nitrogen-based ligands, with a significantly different binding interaction to distinguish it from nitrogen-based analogues. In this report we describe interactions of Sn(IV) porphyrins that bind oxygen-based ligands and for which the Sn(IV)bond;O bond is in slow exchange on the NMR timescale. A series of carboxylate complexes is employed to highlight the structural/geometric features of porphyrin monomers and cyclic oligomers. Where more than one porphyrin unit is present in a molecular scaffold, we report the effect of carboxylate binding on the complex when the two porphyrins contain different metals (typically Sn(IV) and Zn(II)). The unexpected spectroscopic and structural properties of the Sn(2)(9-anthroic acid)porphyrin dimer are also reported.

Journal Article↗
PubMed2003

Construction of multiporphyrin arrays using ruthenium and rhodium coordination to phosphines.

The synthesis of linear multiporphyrin arrays with mono- and bisphosphine-substituted porphyrins as ligand donors and ruthenium(II) or rhodium(III) porphyrins as ligand acceptors is described. With appropriate amounts of the building blocks mixed, linear dimeric and trimeric arrays have been synthesized and analyzed by (1)H NMR and (31)P NMR spectroscopy. The Ru/Rh acceptor porphyrins can be located either at the periphery or in the center of the array. Likewise, the monophosphine porphyrins can be positioned at the periphery, thus allowing a high degree of freedom in the overall composition of the arrays. This way, both donor and acceptor porphyrins can act as chain extenders or terminators. One of the trimeric complexes with two nickel and one ruthenium porphyrin has also been analyzed by X-ray crystallography. Attempts have also been made to synthesize higher order arrays by mixing appropriate amounts of the porphyrins; however, from the NMR data it cannot be concluded if monodisperse five, seven, or nine porphyrin arrays are present or if the solutions are composed of a statistical mixture of smaller and larger arrays.

Journal Article↗
PubMed2003

A self-assembling polymer-bound rotaxane under thermodynamic control.

The thermodynamically controlled self-assembly of a neutral donor-acceptor rotaxane, stoppered via porphyrin coordination and bound to polystyrene beads is described, and the dynamic equilibrium between solid and solution phases has been examined by HR MAS nmr spectroscopy.

Journal Article↗
PubMed2003

Metal-ion induced amplification of three receptors from dynamic combinatorial libraries of peptide-hydrazones.

Three building blocks of general structure (MeO)2 CH-aromatic linker-Pro-amino acid-NHNH2 have been prepared and tested in acid-catalysed dynamic combinatorial libraries. Exposure of these libraries to LiI and NaI led to the amplification of three macrocyclic pseudopeptide receptors. The receptors were isolated and their interactions with LiI and NaI were analysed using NMR, IR and ITC. Binding of the metal ions to the receptors is invariably entropy-driven. Nevertheless, all receptors were found to be flexible with substantial conformational rearrangements accompanying guest binding. This type of receptor is extremely difficult to access through rational design and the fact that dynamic combinatorial chemistry allows facile access to these challenging molecules underlines the power of the dynamic approach.

Combinatorial Chemistry Techniques↗
PubMed2003

Complexation of diphenyl(phenylacetenyl)phosphine to rhodium(III) tetraphenyl porphyrins: synthesis and structural, spectroscopic, and thermodynamic studies.

The coordination of diphenyl(phenylacetenyl)phosphine (DPAP, 1) to (X)Rh(III)TPP (X = I (2) or Me (3); TPP = tetraphenyl porphyrin) was studied in solution and in the solid state. The iodide is readily displaced by the phosphine, leading to the bis-phosphine complex [(DPAP)(2)Rh(TPP)](I) (4). The methylide on rhodium in 3 is not displaced, leading selectively to the mono-phosphine complex (DPAP)(Me)Rh(TPP) (5). The first and second association constants, as determined by isothermal titration calorimetry and UV-vis titrations, are in the range 10(4)-10(7) M(-1) (in CH(2)Cl(2)). Using LDI-TOF mass spectrometry, the mono-phosphine complexes can be detected but not the bis-phosphine complexes. The electronic spectrum of 4 is similar to those previously reported with other tertiary phosphine ligands, whereas (DPAP)(I)Rh(TPP) (6) displays a low energy B-band absorption and a high energy Q-band absorption. In contrast to earlier reports, displacement of the methylide on rhodium in 5 could not be observed at any concentration, and the electronic spectra of 4 and 5 are almost identical. Isothermal titration calorimetry experiments showed that all binding events are exothermic, and all are enthalpy driven. The largest values of DeltaG degrees are found for 6. The thermodynamic and UV-vis data reveal that the methylide and the phosphine ligand have an almost identical electronic trans-influence on the sixth ligand.

Journal Article↗
PubMed2002

Phosphine and phosphonite complexes of a ruthenium(II) porphyrin. 1. Synthesis, structure, and solution state studies.

We have investigated the effect of complexation of different phosphorus ligands on the stability, solid state structure, and spectroscopic properties (NMR, IR, UV-vis) of a 5,15-diphenyl-substituted ruthenium porphyrin, (MeOH)Ru(II)(CO)(DPP) 2 [DPP = 5,15-bis(3',5'-di-tert-butyl)phenyl-2,8,12,18-tetraethyl-3,7,13,17-tetramethylporphyrin]. The ligands used are PPh(3), diphenyl(phenylacetenyl)phosphine (DPAP), bis(diphenylphosphino)acetylene (DPPA), tris(phenylacetenyl)phosphine [(PA)(3)P], and diethyl (phenylacetenyl)phosphonite [PAP(OEt)(2)]. The mono-phosphine complexes (PR(3))Ru(II)(CO)(DPP) are readily formed in solution in quantitative yields. The complexes display association constants ranging from 1.2 x 10(4) M(-1) for PPh(3) to 4.8 x 10(6) M(-1) for PAP(OEt)(2). The weak association of PPh(3) does not correlate with its pK(a), delta((31)P), or cone angle value and is attributed to steric effects. Due to their kinetic lability, which is shown by 2D NMR spectroscopy, and the weakening of the carbonyl ligand via a trans effect, the mono-phosphine complexes could not be isolated. IR spectroscopy gives the relative order of pi-acceptor strength as PPh(3) < DPAP, DPPA < (PA)(3)P < PAP(OEt)(2), whereas the relative order of the sigma-donor strength is PPh(3) < (PA)(3)P < DPAP, DPPA < PAP(OEt)(2), based on the calculated pK(a) values and on the (31)P((1)H) NMR chemical shifts of the ligands. The chemical shift differences in the (31)P9(1)H)) NMR spectra upon ligand binding display a linear correlation with the calculated pK(a) values of the protonated ligands HPR(3)(+); we propose that the pK(a), and probably other electronic properties, of a specific phosphorus ligand can be estimated on the basis of the chemical shift difference Deltadelta((31)P) upon complexation to a metalloporphyrin. The bis-phosphine complexes can be isolated in pure form by crystallization from CHCl(3)-MeOH solutions using excess ligand. Association of the second ligand is in the same order of magnitude as the first binding for the phosphines, but the second phosphonite binding is decreased by a factor of about 100. The solid state structures show only marginal differences in the geometrical parameters. The calculated and the crystallographic cone angles of the ligands generally do not match, apart from the values obtained for PAP(OEt)(2).

Journal Article↗
PubMed2002

Phosphine and phosphonite complexes of a Ru(II) porphyrin. 2. Photophysical and electrochemical studies.

The photophysical and electrochemical properties of a series of mono- and bis-phosphine complexes of a 5,15-diphenyl-substituted ruthenium porphyrin, (MeOH)Ru(II)(CO)(DPP) 1, were investigated. The ligands used were diphenyl(phenylacetenyl)phosphine (DPAP), diethyl (phenylacetenyl)phosphonite [PAP(OEt)(2)], tris(phenylacetenyl)phosphine [(PA)(3)P], and bis(diphenylphosphino)acetylene (DPPA). All complexes display two reversible one-electron oxidations at: 0.61 and 1.0 V vs SCE (1), 0.42-0.51 and 0.97-1.05 V [(PR(3))Ru(II)(CO)(DPP)], and 0.06-0.25 and 0.82-0.95 V [(PR(3))(2)Ru(II)(DPP)]. As predicted by EHMO calculations, the first oxidation is porphyrin or phosphorus centered, whereas the second one is ruthenium centered. Bulk electrolysis at the first oxidation potential yields stable monocations. Simulation of the cyclic voltammogram of (DPAP)Ru(II)(CO)(DPP) in CH(2)Cl(2) demonstrates the kinetic lability of the complex, and the association constant found (K = 1.27 x 10(6) M(-1)) is in accordance with the value determined by UV-vis titration (K = 1.2 +/- 0.3 x 10(6) M(-1)). Coordination of one phosphine ligand to Ru(II)(CO)(DPP) leads to a red shift in both the absorption and luminescence spectra. Shifts are typically 10 nm for the B- and Q-band absorptions and are not affected by the nature of the phosphorus ligand. The intense luminescence of (PR(3))Ru(II)(CO)(DPP), red-shifted by 21-28 nm compared to 1, can be attributed to originate from a (3)(pi,pi) excited state, and it exhibits lifetimes from 150 to 240 micros. In the bis-phosphine complexes (PR(3))(2)Ru(II)(DPP), the Q-band absorption is broadened and does not show any distinct peak. Judged from EHMO calculation, this could arise from a low-energy charge-transfer state involving the phosphorus ligand. The luminescence is efficiently quenched due to radiationless decay from a charge-transfer excited state, involving either the metal center or the phosphorus ligand; an unambiguous assignment could not be made.

Journal Article↗
PubMed2002

Selection and amplification of hosts from dynamic combinatorial libraries of macrocyclic disulfides.

We have discovered two receptors for two different guests from a single dynamic combinatorial library. Each of the two guests amplifies the formation of a tightly binding host at the expense of unfit library members. Small differences in host-guest binding translate into useful differences in amplification. The selected hosts could be readily synthesized using biased dynamic libraries that contain only the right ratio of those building blocks that were selected by the guests. These results establish dynamic combinatorial chemistry as a practical method not only for the discovery but also for the synthesis of new receptors.

Journal Article↗
PubMed2002

Dynamic covalent chemistry.

Dynamic covalent chemistry relates to chemical reactions carried out reversibly under conditions of equilibrium control. The reversible nature of the reactions introduces the prospects of "error checking" and "proof-reading" into synthetic processes where dynamic covalent chemistry operates. Since the formation of products occurs under thermodynamic control, product distributions depend only on the relative stabilities of the final products. In kinetically controlled reactions, however, it is the free energy differences between the transition states leading to the products that determines their relative proportions. Supramolecular chemistry has had a huge impact on synthesis at two levels: one is noncovalent synthesis, or strict self-assembly, and the other is supramolecular assistance to molecular synthesis, also referred to as self-assembly followed by covalent modification. Noncovalent synthesis has given us access to finite supermolecules and infinite supramolecular arrays. Supramolecular assistance to covalent synthesis has been exploited in the construction of more-complex systems, such as interlocked molecular compounds (for example, catenanes and rotaxanes) as well as container molecules (molecular capsules). The appealing prospect of also synthesizing these types of compounds with complex molecular architectures using reversible covalent bond forming chemistry has led to the development of dynamic covalent chemistry. Historically, dynamic covalent chemistry has played a central role in the development of conformational analysis by opening up the possibility to be able to equilibrate configurational isomers, sometimes with base (for example, esters) and sometimes with acid (for example, acetals). These stereochemical "balancing acts" revealed another major advantage that dynamic covalent chemistry offers the chemist, which is not so easily accessible in the kinetically controlled regime: the ability to re-adjust the product distribution of a reaction, even once the initial products have been formed, by changing the reaction's environment (for example, concentration, temperature, presence or absence of a template). This highly transparent, yet tremendously subtle, characteristic of dynamic covalent chemistry has led to key discoveries in polymer chemistry. In this review, some recent examples where dynamic covalent chemistry has been demonstrated are shown to emphasise the basic concepts of this area of science.

Combinatorial Chemistry Techniques↗
PubMed2002

Dynamic combinatorial chemistry.

A combinatorial library that responds to its target by increasing the concentration of strong binders at the expense of weak binders sounds ideal. Dynamic combinatorial chemistry has the potential to achieve exactly this. In this review, we will highlight the unique features that distinguish dynamic combinatorial chemistry from traditional combinatorial chemistry, and that could make a useful addition to the set of combinatorial techniques used in drug discovery.

Combinatorial Chemistry Techniques↗
PubMed2002

Recent developments in dynamic combinatorial chemistry.

Generating combinatorial libraries under equilibrium conditions has the important advantage that the libraries are adaptive (i.e. they can respond to exterior influences in the form of molecular recognition events). Thus, a ligand will direct and amplify the formation of its ideal receptor and vice versa. Proof of principle of this approach has been established using small libraries showing highly efficient amplification of selected receptors. The approach has recently been extended to address folding of macromolecules, including peptides.

Combinatorial Chemistry Techniques↗