Variety Of Other Ligands Research Articles

Ready-to-use room temperature one-pot synthesis of surface-decorated gold nanoparticles with targeting attributes

Gold nanoparticles (AuNPs) can be used in diagnostic and therapeutic applications. The development of facile and fast synthetic approaches is accordingly desirable towards ready-to-use biomedical materials. We report a practical one-pot method for the synthesis in aqueous media and room temperature of surface-decorated AuNPs with enhanced biological responses. The gold ions could be reduced using only polyethyleneimine (PEI) derivatives containing sugar and-or alkyl chains acting simultaneously as reducing and stabilizing agent, without the aid of any other mediator. The process is possibly potentialized by the presence of the amino groups in the polymer chains which further confer colloidal stability. The kinetics of AuNPs nucleation and growth depends on the chemical nature of the polymer chains. Particularly, the presence of lactose moieties conjugated to the PEI chains conducted to surface-decorated AuNPs with low cytotoxicity that are remarkably faster uptaken by HepG2 cells. These cells overexpress asialoglycoprotein (ASGP-R), a galactose receptor. These findings may kick off significant advances towards the practical and ready-to-use manufacturing of functionalized AuNPs towards cell-targeting since the methodology is applicable for a large variety of other ligands that can be conjugated to the same polymer chains.

Biophysical Basis of the Binding of WWOX Tumor Suppressor to WBP1 and WBP2 Adaptors

The WW-containing oxidoreductase (WWOX) tumor suppressor participates in a diverse array of cellular activities by virtue of its ability to recognize WW-binding protein 1 (WBP1) and WW-binding protein 2 (WBP2) signaling adaptors among a wide variety of other ligands. Herein, using a multitude of biophysical techniques, we provide evidence that while the WW1 domain of WWOX binds to PPXY motifs within WBP1 and WBP2 in a physiologically relevant manner, the WW2 domain exhibits no affinity toward any of these PPXY motifs. Importantly, our data suggest that while R25/W44 residues located within the binding pocket of a triple-stranded β-fold of WW1 domain are critical for the recognition of PPXY ligands, they are replaced by the chemically distinct E66/Y85 duo at structurally equivalent positions within the WW2 domain, thereby accounting for its failure to bind PPXY ligands. Predictably, not only does the introduction of E66R/Y85W double substitution within the WW2 domain result in gain of function but the resulting engineered domain, hereinafter referred to as WW2_RW, also appears to be a much stronger binding partner of WBP1 and WBP2 than the wild-type WW1 domain. We also show that while the WW1 domain is structurally disordered and folds upon ligand binding, the WW2 domain not only adopts a fully structured conformation but also aids stabilization and ligand binding to WW1 domain. This salient observation implies that the WW2 domain likely serves as a chaperone to augment the physiological function of WW1 domain within WWOX. Collectively, our study lays the groundwork for understanding the molecular basis of a key protein-protein interaction pertinent to human health and disease.

Biophysical Analysis of Binding of WW Domains of the YAP2 Transcriptional Regulator to PPXY Motifs within WBP1 and WBP2 Adaptors

The YAP2 transcriptional regulator mediates a plethora of cellular functions, including the newly discovered Hippo tumor suppressor pathway, by virtue of its ability to recognize WBP1 and WBP2 signaling adaptors among a wide variety of other ligands. Herein, using isothermal titration calorimery and circular dichroism in combination with molecular modeling and molecular dynamics, we provide evidence that the WW1 and WW2 domains of YAP2 recognize various PPXY motifs within WBP1 and WBP2 in a highly promiscuous and subtle manner. Thus, although both WW domains strictly require the integrity of the consensus PPXY sequence, nonconsensus residues within and flanking this motif are not critical for high-affinity binding, implying that they most likely play a role in stabilizing the polyproline type II helical conformation of the PPXY ligands. Of particular interest is the observation that both WW domains bind to a PPXYXG motif with highest affinity, implicating a preference for a nonbulky and flexible glycine one residue to the C-terminal side of the consensus tyrosine. Importantly, a large set of residues within both WW domains and the PPXY motifs appear to undergo rapid fluctuations on a nanosecond time scale, suggesting that WW-ligand interactions are highly dynamic and that such conformational entropy may be an integral part of the reversible and temporal nature of cellular signaling cascades. Collectively, our study sheds light on the molecular determinants of a key WW-ligand interaction pertinent to cellular functions in health and disease.

Quadruplex DNA: A Promising Drug Target for the Medicinal Inorganic Chemist

Compounds that can bind to and stabilize quadruplex DNA structures in telomeres, or induce formation of such structures from ssDNA, represent an attractive general approach to the treatment of cancer. Until recently most effort in this area has been directed towards the synthesis of organic compounds for this purpose. More recently there has been growing recognition that metal complexes offer a number of potential advantages for the preparation of lead complexes that bind with high affinity and selectivity for quadruplex DNA. This review seeks to discuss the work that has been reported in this area to date. While most early studies focused on metal complexes of porphyrin ligands, during the past 4 years there has been a dramatic increase in the number of papers in the literature examining the potential of mononuclear complexes of a variety of other ligands, particularly Schiff base ligands and those based on phenanthroline, as quadruplex DNA binders and telomerase inhibitors. In addition, there has been growing interest in exploiting supramolecular chemistry to prepare novel multinuclear complexes that bind to this new drug target.

Highly Fluorescent Platinum(II) Organometallic Complexes of Perylene and Perylene Monoimide, with Pt σ-Bonded Directly to the Perylene Core

3-Bromoperylene (BrPer) or N-(2,5-di-tert-butylphenyl)-9-bromo-perylene-3,4-dicarboximide (BrPMI) react with [Pt(PEt(3))(4)] to yield trans-[PtR(PEt(3))(2)Br] (R = Per, 1a; R = PMI, 1b). Neutral and cationic perylenyl complexes containing a Pt(PEt(3))X group have been prepared from 1a,b by substitution of the Br ligand by a variety of other ligands (NCS, CN, NO(3), CN(t)Bu, PyMe). The X-ray structures of trans-[PtR(PEt(3))(2)X] (R = Per, X = NCS (2a); R = PMI, X = NO(3) (4b); R = Per, X = CN(t)Bu (5a)) show that the perylenyl fragment remains nearly planar and is arranged almost orthogonal to the coordination plane: The three molecules appear as individual entities in the solid state, with no π-π stacking of perylenyl rings. Each platinum complex exhibits fluorescence associated to the perylene or PMI fragments with emission quantum yields, in solution at room temperature, in the range 0.30-0.80 and emission lifetimes ∼4 ns, but with significantly different emission maxima, by influence of the X ligands on Pt. The similarity of the overall luminescence spectra of these metalated complexes with the perylene or PMI strongly suggests a perylene-dominated intraligand π-π*emissive state, metal-perturbed by interaction of the platinum fragment mostly via polarization of the Ar-Pt bond.

Halogenated Benzenes Bound within a Non-polar Cavity in T4 Lysozyme Provide Examples of I⋯S and I⋯Se Halogen-bonding

We showed earlier that the mutation of Leu99 to alanine in bacteriophage T4 lysozyme creates an internal cavity of volume ∼ 150 Å 3 that binds benzene and a variety of other ligands. As such, this cavity provides an excellent target to study protein-ligand interaction. Here, we use low-temperature crystallography and related techniques to analyze the binding of halogen-incorporated benzenes typified by C 6F 5X, where X = H, F, Cl, Br or I, and C 6H 5X, where X = H or I was also studied. Because of the increased electron density of fluorine relative to hydrogen, the geometry of binding of the fluoro compounds can often be determined more precisely than their hydrogen-containing analogs. All of the ligands bind in essentially the same plane but the center of the phenyl ring can translate by up to 1.2 Å. In no case does the ligand rotate freely within the cavity. The walls of the cavity consist predominantly of hydrocarbon atoms, and in several cases it appears that van der Waals interactions define the geometry of binding. In comparing the smallest with the largest ligand, the cavity volume increases from 181 Å 3 to 245 Å 3. This shows that the protein is flexible and adapts to the size and shape of the ligand. There is a remarkably close contact of 3.0 Å between the iodine atom on C 6F 5I and the sulfur or selenium atom of Met or SeMet102. This interaction is 1.0 Å less than the sum of the van der Waals radii and is a clear example of a so-called halogen bond. Notwithstanding this close approach, the increase in binding energy for the halogen bond relative to a van der Waals contact is estimated to be only about 0.5–0.7 kcal/mol.

Cu-Catalyzed [4+1] Cycloadditions of Enones with Diazo Compounds

This paper describes the enantio­selective synthesis of 2,3-dihydrofurans through a copper-catalyzed [4+1] cycloaddition of enones and diazo compounds. The use of bpy* (1) as chiral ligand gave the best results when compared to a variety of other ligands including bis(oxazolines), semicorrin and others. Enones containing unsaturated substituents (i.e., aryl and heteroaryl) provided high ee values (87-93% ee), while alkyl-substituted enones gave only modest selectivities (71-78% ee).

Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary-derived cells by protein kinase signaling pathways

Scavenger receptor, class B, type I (SR-BI) mediates binding and internalization of a variety of lipoprotein and nonlipoprotein ligands, including HDL. Studies in genetically engineered mice revealed that SR-BI plays an important role in HDL reverse cholesterol transport and protection against atherosclerosis. Understanding how SR-BI's function is regulated may reveal new approaches to therapeutic intervention in atherosclerosis and heart disease. We utilized a model cell system to explore pathways involved in SR-BI-mediated lipid uptake from and signaling in response to distinct lipoprotein ligands: the physiological ligand, HDL, and a model ligand, acetyl LDL (AcLDL). In Chinese hamster ovary-derived cells, murine SR-BI (mSR-BI) mediates lipid uptake via distinct pathways that are dependent on the lipoprotein ligand. Furthermore, HDL and AcLDL activate distinct signaling pathways. Finally, mSR-BI-mediated selective lipid uptake versus endocytic uptake are differentially regulated by protein kinase signaling pathways. The protein kinase C (PKC) activator PMA and the phosphatidyl inositol 3-kinase inhibitor wortmannin increase the degree of mSR-BI-mediated selective lipid uptake, whereas a PKC inhibitor has the opposite effect. These data demonstrate that SR-BI's selective lipid uptake activity can be acutely regulated by intracellular signaling cascades, some of which can originate from HDL binding to murine SR-BI itself.

Luminescent Complexes of Iridium(III) Containing N∧C∧N-Coordinating Terdentate Ligands

A family of bis-terdentate iridium(III) complexes is reported which contain a cyclometalated, N/\C[wedge]N-coordinating 1,3-di(2-pyridyl)benzene derivative. This coordination mode is favored by blocking competitive cyclometalation at the C4 and C6 positions of the ligand. Thus, 1,3-di(2-pyridyl)-4,6-dimethylbenzene (dpyxH) reacts with IrCl3 x 3H2O to generate a dichlorobridged dimer [Ir(dpyx-N,C,N)Cl(mu-Cl)]2, 1. This dimer is cleaved by DMSO to give [Ir(dpyx)(DMSO)Cl2], the X-ray crystal structure of which is reported here, confirming the N/\C/\N coordination mode of dpyx. The dimer 1 can also be cleaved by a variety of other ligands to generate novel classes of mononuclear complexes. These include charge-neutral bis-terdentate complexes of the form [Ir(N/\C/\N)(C/\N/\C)] and [Ir(N/\C/\N)(C/\N/\O)], by reaction of 1 with C/\N/\C-coordinating ligands (e.g., 2,6-diphenylpyridine and derivatives) and C/\N/\O-coordinating ligands (based on 6-phenylpicolinate), respectively. Treatment of 1 with terpyridines leads to dicationic complexes of the type [Ir(N/\C/\N)(N/\N/\N)]2+, while 2-phenylpyridine gives [Ir(dpyx-N/\C/\N)(ppy-C,N)Cl]. All of the charge-neutral complexes are luminescent in fluid solution at room temperature. Assignment of the emission to charge-transfer excited states with significant MLCT character is supported by DFT calculations. In the [Ir(N/\C/\N)(C/\N/\C)] class, fluorination of the C/\N/\C ligand at the phenyl 2' and 4' positions leads to a blue-shift in the emission and to an increase in the quantum yield (lambda(max) = 547 nm, phi = 0.41 in degassed CH(3)CN at 295 K) compared to the nonfluorinated parent complex (lambda(max) = 585 nm, phi = 0.21), as well as to a stabilization of the compound with respect to photodissociation through cleavage of mutually trans Ir-C bonds. [Ir(dpyx-N/\C/\N)(ppy-C,N)Cl] is an exceptionally bright emitter: phi = 0.76, lambda(max) = 508 nm, in CH(3)CN at 295 K. In contrast, the [Ir(N/\C/\N)(C/\N/\O)] complexes are much less emissive, shown to be due to fast nonradiative decay of the excited state, probably involving reversible Ir-O bond cleavage. The [Ir(N/\C/\N)(N/\N/\N)]2+ complexes are very feeble emitters even at 77 K, probably due to the almost exclusively interligand charge-transfer nature of the lowest-energy excited state in these complexes.

Base-Free Asymmetric Transfer Hydrogenation of Aromatic Ketones

A highly enantioselective hydrogenation of aromatic ketones using IrH(CO)(PPh3)3 and a tetradentate PNNP-type ligand is described. The ability to perform the reaction in the absence of base allows a wider substrate scope. A variety of other ligands (binary and PNNP-type) and metal hydride complexes were investigated.

α2-macroglobulin: an evolutionarily conserved arm of the innate immune system

All animals and plants have immune systems that protect them from the diversity of pathogens that would otherwise threaten their survival. The different components of the immune system may inactivate the pathogens themselves or promote the inactivation and clearance of toxic products produced by the pathogens. An important category of virulence factors of bacterial and prokaryotic pathogens are the proteases, which act to facilitate the invasion of the pathogens and to promote their destructive growth in the host organism. The present review concentrates on the comparative biology of an evolutionarily conserved arm of the immune system, the protein, α2-macroglobulin. α2-Macroglobulin is an abundant protein of the plasma of vertebrates and members of several invertebrate phyla and functions as a broad-spectrum protease-binding protein. Protease-conjugated α2-macroglobulin is selectively bound by cells contacting the body fluids and α2-macroglobulin and its protease cargo are then internalized and degraded in secondary lysosomes of those cells. In addition to this function as an agent for protease clearance, α2-macroglobulin binds a variety of other ligands, including several peptide growth factors and modulates the activity of a lectin-dependent cytolytic pathway in arthropods.

Carboxylate-Bridged Diiron(II) Complexes: Synthesis, Characterization, and O2-Reactivity of Models for the Reduced Diiron Centers in Methane Monooxygenase and Ribonucleotide Reductase

Diiron(II) complexes with an oxygen-rich coordination environment were assembled with the dinucleating dicarboxylate ligands m-xylylenediamine bis(Kemp's triacid)imide (H2XDK) and the more soluble analogue m-xylylenediamine bis(propyl Kemp's triacid)imide (H2PXDK). X-ray crystallographic analysis revealed that, in most of the complexes, only one monodentate N-donor ligand is bound to each iron(II) ion. In addition to XDK and PXDK, a variety of other ligands bridge the dimetallic core including chloride, fluoride, triflate, or carboxylate. The tris(carboxylate-bridged) complexes [Fe2(μ-XDK)(μ-O2CPh)(ImH)2(O2CPh)(MeOH)] (3) and [Fe2(μ-O2CC(CH3)3)(μ-PXDK)(N-MeIm)2(O2CC(CH3)3)] (4) have the same ligand composition as the diiron(II) cores in the hydroxylase component of methane monooxygenase (MMO) and in the R2 protein of ribonucleotide reductase (RNR). The coordination environments of the two iron centers in 3 and 4 are inequivalent, with one iron being 6-coordinate and the other being 4-coordinate. The bridging benzoate and pivalate ligands have an unusual coordination mode with a Fe−O−C bond angle close to 180°. Fits of magnetic susceptibility data collected for several of the complexes between 300 and 4 K indicated that the two iron(II) centers are weakly antiferromagnetically coupled with a coupling constant which does not depend on the nature of the bridging ligands. Mössbauer spectra of polycrystalline and frozen THF solution samples of 4 exhibited two overlapping doublets of equal intensity, reflecting the different coordination environments of the two iron(II) ions. The nearly identical Mössbauer parameters for the solid and frozen solution samples indicate that the dinuclear core remains intact upon dissolution. Stopped-flow studies of the reaction of 3 and 4 with O2 in THF showed the rapid formation (kψ ≈ 74 s-1 for 3 at 202.5 K and kψ ≈ 300 s-1 for 4 at 197 K) of colored intermediates with broad absorption maxima near 660 and 670 nm, respectively. These values are characteristic of peroxo-to-iron charge-transfer bands and similar to that observed for the (μ-peroxo)diiron(III) intermediate (Hperoxo) in the MMO reaction cycle.

Investigation of enantioselective ligand–protein binding and displacement interactions using capillary electrophoresis

AbstractWhen a protein such as human serum albumin is added to the separation buffer in capillary electrophoresis, the mobility of solutes which bind to that protein may be altered. The change in mobility of the solute is a function both of the strength of the binding interaction, and the difference in mobility between the free solute and protein additive. By adding other ligands which themselves bind to the protein, the strength of the solute–protein binding may be modified, leading to a measurable change in the mobility of the solute. These effects are particularly striking for chiral compounds, where enantioselectivity may be completely lost on addition of a competitive ligand. Capillary electrophoresis with human serum ablumin as a buffer additive was used to separate the enantiomers of benzoin and three phenothiazine derivatives. A comparison of the binding of (S)‐benzoin to human serum albumin as determined by capillary electrophoresis and by ultrafiltration was made. A variety of other ligands were then added to the buffer along with the protein, and the effects on mobility and enantioselectivity were studied. The displacers included (R)‐ and (S)‐oxazepam hemisuccinate, (R)‐ and (S)‐warfarin, nitrazepam, phenylbutazone, and octanoic acid. From the results obtained, it seems that capillary electrophoresis may be a useful, rapid method to screen for drug–drug interactions. There are some advantages of using this technique to study protein–ligand interactions: Only very small amounts of ligand are needed (useful when dealing with metabolites); for chiral compounds, if protein binding is stereoselective, then the method is also stereoselective, so single enantiomers are not needed; finally, measurements are obtained in solution, without the need for immobilization of the protein. A disadvantage is that the ligand and protein must have significantly different electrophoretic mobilities. © 1994 Wiley‐Liss, Inc.

Role of protein conformation changes and transphosphorylations in the function of Na+/K(+)-transporting adenosine triphosphatase: an attempt at an integration into the Na+/K+ pump mechanism.

The particular aim of the review on some basic facets of the mechanism of Na+/K(+)-transporting ATPase (Na/K-ATPase) has been to integrate the experimental findings concerning the Na(+)- and K(+)-elicited protein conformation changes and transphosphorylations into the perspective of an allosterically regulated, phosphoryl energy transferring enzyme. This has led the authors to the following summarizing evaluations. 1. The currently dominating hypothesis on a link between protein conformation changes ('E1 in equilibrium with E2') and Na+/K+ transport (the 'Albers-Post scheme') has been constructed from a variety of partial reactions and elementary steps, which, however, do not all unequivocally support the hypothesis. 2. The Na(+)- and K(+)-elicited protein conformation changes are inducible by a variety of other ligands and modulatory factors and therefore cannot be accepted as evidence for their direct participation in effecting cation translocation. 3. There is no evidence that the 'E1 in equilibrium with E2' protein conformation changes are moving Na+ and K+ across the plasma membrane. 4. The allosterically caused ER in equilibrium with ET ('E1 in equilibrium with E2') conformer transitions and the associated cation 'occlusion' in equilibrium with 'de-occlusion' processes regulate the actual catalytic power of an enzyme ensemble. 5. A host of experimental variables determines the proportion of functionally competent ER enzyme conformers and incompetent ET conformers so that any enzyme population, even at the start of a reaction, consists of an unknown mixture of these conformers. These circumstances account for the occurrence of contradictory observations and apparent failures in their comparability. 6. The modelling of the mechanism of the Na/K-ATPase and Na+/K+ pump from the results of reductionistically designed experiments requires the careful consideration of the physiological boundary conditions. 7. Na+ and K+ ligandation of Na/K-ATPase controls the geometry and chemical reactivity of the catalytic centre in the cycle of E1 in equilibrium with E2 state conversions. This is possibly effected by hinge-bending, concerted motions of three adjacent, intracellularly exposed peptide sequences, which shape open and closed forms of the catalytic centre in lock-and-key responses. 8. The Na(+)-dependent enzyme phosphorylation with ATP and the K(+)-dependent hydrolysis of the phosphoenzyme formed are integral steps in the transport mechanism of Na/K-ATPase, but the translocations of Na+ and K+ do not occur via a phosphate-cation symport mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)

G protein diversity: a distinct class of alpha subunits is present in vertebrates and invertebrates.

Heterotrimeric guanine nucleotide-binding proteins (G proteins) are integral to the signal transduction pathways that mediate the cell's response to many hormones, neuromodulators, and a variety of other ligands. While many signaling processes are guanine nucleotide dependent, the precise coupling between a variety of receptors, G proteins, and effectors remains obscure. We found that the family of genes that encode the alpha subunits of heterotrimeric G proteins is much larger than had previously been supposed. These novel alpha subunits could account for some of the diverse activities attributed to G proteins. We have now obtained cDNA clones encoding two murine alpha subunits, G alpha q and G alpha 11, that are 88% identical. They lack the site that is ordinarily modified by pertussis toxin and their sequences vary from the canonical Gly-Ala-Gly-Glu-Ser (GAGES) amino acid sequence found in most other G protein alpha subunits. Multiple mRNAs as large as 7.5 kilobases hybridize to G alpha q specific probes and are expressed at various levels in many different tissues. G alpha 11 is encoded by a single 4.0-kilobase message which is expressed ubiquitously. Amino acid sequence comparisons suggest that G alpha q and G alpha 11 represent a third class of alpha subunits. A member of this class was found in Drosophila melanogaster. This alpha subunit, DG alpha q, is 76% identical to G alpha q. The presence of the Gq class in both vertebrates and invertebrates points to a role that is central to signal transduction in multicellular organisms. We suggest that these alpha subunits may be involved in pertussis toxin-insensitive pathways coupled to phospholipase C.

Kinetics of extremely fast ligand-exchange reactions with methylmercury(II)-nitrothiophenolate complexes: rate-equilibria correlations

The kinetics of the CH 3Hg(II) transfer from two nitrothiophenolates (4-nitro-2-sulfonato-thiopheno-late and 4-nitro-3-carboxylato-thiophenolate) to a wide variety of other ligands and the reverse reaction have been investigated by means of the temperature-jump and stopped-flow methods. Over the whole wide range of equilibrium constants the exchange reactions are almost diffusion-controlled, even in the isergonic region. The protonated S-donors can also initiate directly the ligand-exchange reactions. The rate constants for the thiophenols are always smaller than those for the thiophenolates. The reactivity of the protonated S-donors is strongly dependent on the nature of the ligand to be displaced. Several features of the reaction mechanisms involved and their relevance for the transport of CH 3Hg(II) in natural systems are discussed.

Four-coordinated palladium(II) and platinum(II) complexes containing the Lewis-acid {M(S 2CNHR)(PR 3′)} group combined with a variety of other ligands

A new series of four-coordinated Pd(II) and Pt(II) complexes in which the Lewis-acid (14-electron) {M(S 2CNHR)(PR 3′)} group is combined with a variety of other ligands (such as RHNCS 2 −, I −, SCN −, SnCl 2I −) has been synthesised and studied. The structures of the new compounds are discussed in relation to their specroscopic, magnetic and thermal properties. In the case of [M(S 2CNHR) 2(PR 3′)] complexes both the spectroscopic data (IR, 1H NMR, UV-Vis) and their thermal behaviour strongly suggest the coexistence of two kinds of gem-disulphide ligands, one acting as a bidentate ligand and the other one as a unidentate. Also it was confirmed that the chemical behaviour of the bis(N-alkyldithiocarbamato) complexes of Pd(II) and Pt(II) towards tertiary phosphines is similar to that of the isoelectronic xanthate complexes rathe than to the bis(N,N-dialkyldithiocarbamato) complexes.

Specific plasma membrane receptors for reovirus on rat pituitary cells in culture.

Specific cellular and host tropism is a characteristic property of many viruses mediated by the interaction of viral attachment proteins with components of the plasma membrane of the cell. We have studied the binding of virus to cells quantitatively by using type 3 reovirus labeled with 125I and GH4C1 pituitary cells in culture. Binding was rapid at both 4 degrees and 15 degrees C and was stable over a 9-h period. Unlabeled virus inhibited binding of the labeled virus in a dose-dependent manner. Scatchard analysis revealed 4,200 viral binding sites/cell with an apparent affinity of 1.2 X 10(-11) M. Also, binding of type 3 reovirus was inhibited by antibodies directed against the viral hemagglutinin and partially inhibited by type 2 reovirus, but was unaffected by type 1 reovirus or a variety of other ligands that bind to receptors on GH4C1 cells. These data indicate that reovirus binds to a high affinity, specific receptor on target cells, which may control its tropism and ultimate disease expression.

Influence of solvation on the initial and transition states for anation reactions of transition-metal complexes in mixed aqueous solvents

A free-energy cycle has been applied to the rate-determining step in mixed aqueous solvents for the anation of cations having all aquo-ligands or only one aquo-ligand together with a variety of other ligands. Combining rate data with activities of water and calculated values for the equilibrium constants for outer-sphere complexes of the incoming ligand with the cation in the mixture, the relative effects of changes of solvation in the initial and transition states can be assessed. At mole fractions of co-solvent less than those where sharp structural changes occur in the mixture, changes of solvation in either the initial or in the transition state may dominate, depending on the identity of the incoming ligand and of the complex cation; but, in general, at mole fractions of co-solvent higher than those where the sharp changes in solvent structure occur, changes in solvation in the initial state have a dominant effect on the rates.

Kinetics of Extremely Fast Ligand Exchange Reactions with Methylmercury(II)‐complexes of 1‐Methylpyridine‐2‐thione and 1‐Methyl‐quinaldine‐4‐thione: Rate‐Equilibria Correlations

AbstractMethylmercury(II) transfer from two heterocyclic thiones to a wide variety of other ligands and the reverse reaction have been investigated by the temperature‐jump method. The reactions are almost diffusion controlled, even when the free energy difference is negligible. The only exceptions are reactions to and from hydroxide. They are about hundred times slower than those with other ligands of comparable stability at zero free energy difference. This is in agreement with the behaviour of hydroxide in other methylmercury(II) exchange reactions. They follow an associative reaction mechanism. An empirical correlation of rate‐and equilibrium‐constants for atom transfer reactions is proposed. This equation shows some similarities to that of the Marcus type for atom transfer. However, the proposed equation not only describes reactions governed by an associative mechanism, but also those of dissociative type and cases between the two extremes.