Divalent Sites Research Articles

Combination of monovalent and divalent sites on an associating species: Application to water

AbstractThis contribution is in honor of Professor Keith E. Gubbins, an international leader in developing advances in statistical mechanics and molecular simulation for engineering applications. The research presented here extends the SAFT model that Chapman proposed and developed while a graduate student with Professor Gubbins. In this manuscript, a thermodynamic perturbation theory within a multi‐density formalism framework is extended to model species with a combination of monovalent and divalent association sites. Theory predictions are verified with Monte Carlo simulation results for different conditions of temperature, density, and angular size of the divalent site. The theory is applied to model water, where the two lone pairs of electrons on the oxygen atom are represented with a divalent site that includes cooperative hydrogen bonding. The theory results are in good agreement with experiments for saturated densities, vapor pressure, internal energy, and extent of hydrogen bonding.

Structure of Sonic Hedgehog protein in complex with zinc(II) and magnesium(II) reveals ion-coordination plasticity relevant to peptide drug design.

The Hedgehog pathway is an essential cell-signaling paradigm implicated in cancer tumorigenesis and the developmental disorder holoprosencephaly, making it an attractive target for therapeutic design. The N-terminal domain of the Sonic Hedgehog protein (Shh-N) is the essential signaling molecule in the Hedgehog pathway. In this role Shh-N interacts with its cognate membrane receptor Patched, as well as the regulatory proteins HHIP and CDO, by utilizing interfaces harboring one or more divalent ions. Here, the crystal structure of human Shh-N is presented at 1.43 Å resolution, representing a landmark in the characterization of this protein. The structure reveals that the conserved Zn2+-binding site adopts an atypical octahedral coordination geometry, whereas an adjacent binding site, normally occupied by binuclear Ca2+, has been supplanted by a single octahedrally bound Mg2+. Both divalent sites are compared with those in previous Shh-N structures, which demonstrates a significant degree of plasticity of the Shh-N protein in terms of divalent ion binding. The presence of a high Mg2+ concentration in the crystallization medium appears to have influenced metal loading at both metal ion-binding sites. These observations have technical and design implications for efforts focused on the development of inhibitors that target Shh-N-mediated protein-protein interactions.

White light emission through efficient energy transfer from Ce3+ to Dy3+ ions in Ca3Mg3(PO4)4 matrix aided by Li+ charge compensator

In this work, we have comprehensively explored the energy transfer process between Ce3+ and Dy3+ ions doped in Ca3Mg3(PO4)4 host lattice. The phosphors were synthesized by facile urea-assisted combustion method. The charge imbalance, produced due to doping of trivalent lanthanides in the divalent sites of the host lattice, has been compensated by adding Li+ charge compensator. The structural characterization by Rietveld refinement, morphological and FTIR studies were performed on the as-prepared Ca2.96Mg3(PO4)4:0.01Ce3+, 0.01Dy3+, 0.02Li+ phosphor. The diffuse reflectance spectra and the photoluminescence spectra of the prepared phosphors and the electron-vibration interaction (EVI) parameters of Ca3Mg3(PO4)4:Ce3+,Li+ phosphor were thoroughly analysed. Ca3Mg3(PO4)4:Ce3+,Dy3+,Li+ phosphor exhibited its ability to produce white light emission at UV excitation wavelength 316nm. The codoping of Ce3+ ions enhanced the PL emission intensity of Dy3+ by ten times as compared to the intensity obtained for the samples that were singly-doped with Dy3+. The results suggest the use of single-phased Ca2.96Mg3(PO4)4:0.01Ce3+, 0.01Dy3+, 0.02Li+ phosphor as potential white light emitting phosphor.

Preparation and characterization of di-(μ2-CH3COO-κ2O:O′)-tetrakis[μ3-methoxo-2,4-pentanedionatometal(II,III)] complexes

Three new complexes with general formula di-(μ2-CH3COO-κ2O:O′)-tetrakis[μ3-methoxo-2,4-pentanedionatometal(II,III)] (M=Co(III); Co(II), Ni(II), Zn(II)), analogues of the previously reported complex di-(μ2-CH3COO-κ2O:O′)-tetrakis[μ3-methoxo-2,4-pentanedionatocobalt(II,III)] ([Co4(acac)4(CH3COO)2(μ3-OCH3)4]), have been prepared and characterized with X-ray crystallography, mass spectrometry and magnetic susceptibility measurements. The complexes show the cubane type structure with two cobalt(III) sites and two divalent sites, in some cases exhibiting partial occupancy. Susceptibility data indicate that the two divalent sites are weakly ferromagnetically coupled in [Co2.5Ni1.5(acac)4(CH3COO)2(μ3-OCH3)4], J=+3.2cm−1 (H=−2JexS1.S2).

Cluster perturbation theory for the self-assembly of associating fluids into complex structures.

Wertheim's two-density thermodynamic perturbation theory (TPT) has proven to be an indispensable statistical mechanical tool in the description of associating fluids with a single association site. TPT was developed to enforce the monovalence of the hydrogen bond and only recently has been extended to account for divalent association sites. It has been shown through experiment and molecular simulation that certain one-site associating fluids can self-assemble into complex extended supramolecular structures as a result of multiple bonding of association sites. In this paper we reorganize TPT into a form that is more easily applied to complex associated structures. The derived theory is general to all possible self-assemble structures. We obtain the free energy and bonding fractions in a general way in terms of single-cluster partition functions and averages. The new formalism removes any reference to graph theory allowing for the conceptually straightforward application of the two-density formalism to complex self-assembled structures.

General Insights into Structural Evolution of Layered Double Hydroxide: Underlying Aspects in Topochemical Transformation from Brucite to Layered Double Hydroxide

The topochemical transformation from transition-metal brucite hydroxide (Co(1-x)Fe(x)(OH)(2), Co(OH)(2), Co(1-x)Ni(x)(OH)(2)) to corresponding (Co(2+)-(Co(3+))-Fe(3+), Co(2+)-(Ni(2+))-Co(3+)) LDH under oxidizing halogen agents (iodine, bromine) exhibits different staging phenomena depending on the metallic composition/ratio in starting brucite. A plausible charge hopping mechanism based on valence interchange between redoxable charge center (Fe(3+)/Co(3+)) and neighboring divalent sites in the host sheet is proposed to understand the restoration of electron donor sites at the interface between brucite crystallites and halogen agents, which ensures a continual oxidative reaction, and a staged intercalation/diffusion of in situ reduced halide anions into the interlayer gallery commensurate with the host charge propagation. The discussion on the correlation between staging product and metallic composition/ratio offers a general perspective and new insights into M(2+)/M(3+) ratio and cation ordering, host layer charge, and phase evolution in LDH structure.

Work function of the mixed-valent manganese perovskites

We have performed resistivity and work function measurements on a series of samples with Ln0.7D0.3MnO3 composition, where Ln is a lanthanide (La, Pr, or Nd) and D is a nominally divalent ion (Sr, Ca, or Pb). The resistivity measurements are, within some small variation, in agreement with those previously reported for polycrystalline samples of similar composition. The measurement of a work function in air is often difficult to reproduce, mainly owing to the fact that it is a surface probe and can be modified significantly by attachment of contaminants from the atmosphere. Here we have obtained reproducible results that are slightly more stable than the reference metals used in the measurements. This required the introduction of a higher order correction to a common Kelvin probe experimental procedure. Another factor contributing to the high quality of the results is the low carrier density of the conducting oxides. This allows greater penetration of quasistatic electric fields. The work function results here are in overall agreement with previous photoemission work that determined an approximate electron binding energy. We find the best correlation of increased work function is to strain introduced by larger divalent ions and smaller Lanthanide ions. We conclude that the work function is dominated by electrons near the divalent site, and this is interpreted in terms of strain modifying the coulomb energy of the electronic states.

Structural and Functional Characterization of Redox Mn and Co Sites in AlPO Materials and Their Role in Alkane Oxidation Catalysis

energy occurred concurrently and at similar rates, indicating excellent agreement between these techniques. No H2 Oo r CO 2 were detected during treatment in H2 or CO, respectively, indicating that reduction from Me 3+ to Me 2+ occurred by introduction of protons. These protons are fully removed by treatment in O2 to 773 K, and O2-H2 redox cycles involving reversible proton formation suggest that cations reside within AlPO framework positions, in which protons reside as charge balancing cations at Me 2+ -O-P bridges. H2 consumption rates measured during H2-TPR could be accurately described by Arrhenius-type behavior, and H2/Me ratios showed that only a fraction of all Me cations undergo reversible redox cycles. This fraction was 0.86 for MnAPO-18 (atomic Mn/P ) 0.05); it decreased from 0.68 to 0.40 for MnAPO-5 as Mn/P ratios increased from 0.028 to 0.10. For CoAPO-18 with 0.028 Co/P and CoAPO-5 with 0.40 Co/P, the fractions of redox sites were 0.64 and 0.40, respectively. UV-visible spectra showed no detectable Me 3+ features after thermal treatment in H2. Thus, cations that do not undergo redox cycles remain as permanently divalent cations throughout O2-H2 cycles. The redox-active fraction also decreased during repeated H 2-O2 redox cycles above 773 K, indicating that redox cations convert into permanently divalent sites. This conversion coincides with the evolution of H2O during H2 treatments above 773 K. These findings together with the effects of Me/P ratio on the redox fraction are consistent with a mechanism in which OH groups at divalent framework cation sites recombine to form H2O and an oxygen vacancy. Cyclohexanol and cyclohexanone formation rates during liquid-phase cyclohexane oxidation with O2 on MnAPO-5 samples increased linearly with the number of redox-active sites, suggesting that elementary steps of cyclohexane oxidation involve cycling between Me 2+ and Me 3+ , and require cation sites able to reversibly form charge balancing cationic species.

Occupancy and site distribution of europium in barium magnesium aluminate by151EuMössbauer spectroscopy

${\mathrm{BaMgAl}}_{10}{\mathrm{O}}_{17}:$ ${\mathrm{Eu}}^{2+}$ (BAM) is a commercial, blue emitting lamp phosphor activated by ${\mathrm{Eu}}^{2+}.$ It is usually assumed that the Eu ions substitute for Ba ions occupying the Beevers-Ross site in the \ensuremath{\beta}-alumina structure. We have investigated this phosphor with varying europium concentrations and different synthesis conditions using ${}^{151}\mathrm{Eu}$ M\ossbauer spectroscopy. Analysis of the M\ossbauer line shapes reveals a pentamodal (or higher) site distribution consisting of three ${\mathrm{Eu}}^{2+}$ sites, one (or two) ${\mathrm{Eu}}^{3+}$ site(s), and a mixed valent site whose isomer shift lies in between those for the divalent and trivalent ions. The observed quadrupole coupling constants for the divalent ions are larger than any other reported to date in any lattice. Based on calculations of the nuclear quadrupole coupling constants by a full potential band-structure method reported recently, the divalent sites are identified with occupancy of the Beevers-Ross, anti-Beevers-Ross, and mid-oxygen sites in the \ensuremath{\beta}-alumina structure. Oxidative degradation of the divalent ions due to the thermal treatment in air was also studied, and a preliminary analysis of how various sites evolve during this process is also presented.

Enhanced V K3 + center afterglow in MgAl 2O 4 by doping with Ce 3+

Ceramic samples of Ce 3+-doped and undoped MgAl 2O 4 have been prepared and studied. Persistent phosphorescence of lifetime longer than 10 h has been observed at 520 nm in the Ce 3+-doped sample. We have identified the long persistence as arising from V K 3+ centers in MgAl 2O 4. The V K 3+ center is a hole trapped at a divalent site. The V K 3+ emission results from the recombination of electrons from the conduction band with holes located at the V K 3+ centers 2.4 eV below the MgAl 2O 4 conduction band. Thermoluminescence spectra of the two samples have also been studied. Thermoluminescence peaks in the undoped MgAl 2O 4 sample are found at 41°C (0.43 eV) and 238°C (0.92 eV), and have been identified as arising from an electron and a hole trap, respectively. Doping with Ce 3+ leads to the formation of two additional thermoluminescence peaks, at 14°C (0.3 eV) and 131°C (0.45 eV), both related to electron traps. The Ce 3+ ions greatly enhance the afterglow by increasing the population of trapped electrons and holes.

Study of the iron/trimesic acid system for the hydrothermal synthesis of hybrid materials

Two divalent iron trimesates were synthesized hydrothermally at 453 K for 72 hours under autogenous pressure using 1,3,5-benzenetricarboxylic acid (or trimesic acid, symbolized by BTC-H3). The first one, [Fe(H2O)4(BTC-H2)2], is molecular and crystallizes in the monoclinic space group P21/c (no. 14) with cell parameters at 293 K: a = 5.1572(3) A, b = 13.0703(8) A, c = 15.2673(10) A, β = 97.209(2)°, Z = 2. The second formulated [Fe3(H2O)12(BTC)2] is one-dimensional; it crystallizes in the monoclinic space group C2 (no. 5) with the following cell parameters at 293 K: a = 17.5592(4) A, b = 12.9874(2) A, c = 6.6031(1), β = 112.004(1)°, Z = 2. Its structure is based on isolated undulating chains which are organized in such a way that they seem to built sheets. Mossbauer spectrometry confirmed the presence of two divalent iron sites in agreement with crystallographic results and also that this compound remains paramagnetic till 4.2 K.

Mutational analysis of the interaction between active site residues and the loop region in mammalian purple acid phosphatases.

Mammalian purple acid phosphatases (PAPs) can be divided into two groups, which exhibit distinct spectroscopic and kinetics properties: PAPs that consist of a single 36 kDa polypeptide, and PAPs that have undergone limited proteolysis to give two fragments with masses of 16 and 20 kDa, respectively. Proteolysis results in an increase in enzymatic activity, an increase in the optimal pH for activity, and a change in the g(z)() value of the characteristic EPR spectrum of the mixed-valence binuclear iron center. It has been proposed that these changes are due to the loss of interactions between Asp146 in an exposed loop region and active site residues upon proteolysis. In the present study, site-directed mutagenesis of Asp146 in recombinant rat bone PAP (recRPAP) has confirmed this hypothesis. Conversion of Asp146 into Ala, which eliminates the interaction of the side chain with the active site, resulted in an enzyme with properties typical of PAPs isolated in proteolytically cleaved forms. The Asp146Asn and Asp146Glu mutants were also prepared and examined to assess the effects of altered electrostatic interactions and side-chain length. Limited proteolysis of all three mutant enzymes with cathepsin L resulted in a significant increase in catalytic activity. Thus, although the interaction between Asp146 and (an) active site residue(s) is the major factor responsible for the low catalytic activity of uncleaved PAPs, other interactions are also important. Since both p-nitrophenyl phosphate and osteopontin, a potential in vivo substrate, show the same level of activation, the observed increase in catalytic activity upon proteolysis is likely to be due to electrostatic rather than steric effects. EPR spectra of FeZn-recRPAP before and after cleavage by cathepsin L suggest that cleavage primarily affects the divalent metal site. The observation that pK(es,1) is also sensitive to changes at the divalent site is consistent with the proposal that the nucleophilic hydroxide is that bridging the divalent and trivalent metals.

Cw/pulsed ESR study of bis[dianthrylcarbene] coupled by 1,4-diethynylbenzene

Cw and pulsed ESR spectroscopy have been applied to bis[dianthrylcarbene] coupled by 1,4-diethynylbenzene in order to investigate electronic and molecular structures of the biscarbene. Spin multiplicity of the biscarbene was identified by 2D-Electron Spin Transient Nutation (2D-ESTN) spectroscopy. 2D-ESTN spectra showed that the biscarbene has a thermally accessible excited triplet state. It is concluded that the two dianthrylcarbene units are antiferromagnetically coupled through 1,4-diethynylbenzene. A fine-structure parameter D of the triplet state determined by the spectral simulation was fairly large compared with that expected from a distance between the two localized non-bonding electron spins on the divalent carbons, indicating an unusually large delocalization effect of the π-electron spin from the carbene sites to a 1,4-ethynylbenzene unit and dianthryl moieties. A large amount of the delocalization arises from the perpendicular conformation of the n-conjugations at the divalent carbon sites.

A Strongly Coupled Mixed Valence State Between Ru3 Clusters. Intramolecular Electron Transfer on the Infrared Vibrational Time Scale in a Pyrazine (pz) Bridged Dimer of Triruthenium Clusters, [{Ru3(μ3-O)(μ-CH3CO2)6(CO)(abco)}2(μ-pz)] (abco = 1-azabicyclo[2,2,2]octane)

Abstract A pyrazine bridged dimer of triruthenium clusters [{RuIII2RuII(μ3-O)(μ-CH3CO2)6(CO)(abco)}2(μ-pz)] (abco =1-azabicyclo[2,2,2]octane, pz = pyrazine) gives an inter-cluster mixed valence state upon one electron reduction. The splitting of the reduction waves in cyclic voltammetry, ΔE, was 470 mV. This corresponds to a comproportionation constant for formation of the mixed valence state of 9.0 × 107. The IR spectrum of the mixed valence species in the ν(CO) region, measured by reflectance IR spectroelectrochemistry, showed a completely coalesced ν(CO) band. This represents delocalized redox behavior on the infrared vibrational timescale. The rate constant for intramolecular electron transfer was estimated to be 1 × 1012 s-1 at -18 °C by simulating the ν(CO) absorption bandshape. The mixed valence complex showed an intervalence charge transfer (ICT) band at 12500 cm-1. Hush analysis provides a spectroscopic estimate of HAB to be 2490 cm-1. Crystal structures of [{RuIII2RuII(μ3-O)(μ-CH3CO2)6(CO)(abco)}2(μ-pz)]·2CH2Cl2 and its precursor, [RuIII2RuII(μ3-O)(CH3CO2)6(CO)(abco)2]·CH2Cl2, were determined by X-ray crystallography. Trends in Ru-O(oxo) and Ru-O(acetate) distances in these compounds show that the divalent site is localized on the Ru center attached to the carbonyl ligand.

Direct Evidence of the Spin Contraction in the Limited-Size Ferrimagnetic Organic Spin System: Determination of the Spin Densities at the Divalent Carbon and Theoretical Calculation of the Spin Contraction

In order to clarify the quantum spin contraction in the limited-size organic spin systems, we have directly determined the σ and π spin densities on the 13C-isotope labeled divalent carbon site of an organic high-spin molecule, 4-(diphenylmeuiylene)-4′-[m-phenylenebis(phenylmethylene)] ether 1. 1 is the most simple model compound for topologically controlled ferrimagnetic spin ordering. The magnitude of the spin density on the divalent carbon site in the diphenylmethylene moiety of 1 is almost one-half of that of diphenylmethylene molecule. This finding gives a direct evidence of the spin contraction expected as a quantum effect on the limited-size ferrimagnetic spin system. We have also carried out the theoretical calculation of the spin-densities, spin-energies, and spin functions for the ferrimagnetic spin chain systems (-SA-SB-SA-SB- … SA≠SB) with different chain lengths by the exact numerical calculation. With increasing number of the repeating unit -SA-SB-, the spin contraction has been recovered. The size dependency of the quantum spin contraction is discussed based on the theoretical calculation.

Suppression of superconductivity in theR(Ba1−zRz)2Cu3O7+δ(R=Pr,Nd) system

Structural and superconducting behavior of samples prepared with the nominal compositions of Nd${}_{1.05}$(Ba${}_{1\ensuremath{-}z}$Pr${}_{z}{)}_{1.95}$Cu${}_{3}$O${}_{7+\ensuremath{\delta}}$ has been investigated by neutron-diffraction and dc magnetization measurements. Neutron data refined by the Reitveld method showed that there is mixing of the rare-earth $(R)$ ions with a substantial fraction of the Pr going to the normal $R$ site in the $R$Ba${}_{2}$Cu${}_{3}$O${}_{7+\ensuremath{\delta}}$-type structure and a corresponding fraction of the Nd going to the Ba site. Structural changes due to the trivalent $R$ ions going to the Ba site are very similar to those observed in the Nd${}_{1+x}$Ba${}_{2\ensuremath{-}x}$Cu${}_{3}$O${}_{7+\ensuremath{\delta}}$ (Nd123ss), indicating that Pr behaves like other trivalent $R$'s on the divalent Ba site. Magnetization measurements show that the depression in ${T}_{c}$ is more pronounced for the Pr bearing samples than that for Nd123ss for the same number of trivalent ions on the Ba site. However, by correcting the changes in ${T}_{c}$ for the depression associated with the fraction of Pr on the $R$ site, the depression in ${T}_{c}$ per trivalent ion on the divalent site is found to be identical to that in other light $R$123ss. Thus the depression in superconductivity in this series of samples is due to two independent effects: (1) Pr on the $R$ site and (2) hole localization due to trivalent $R$ ions on the Ba site. In this respect, Pr on the Ba site appears to behave like all the other trivalent $R$ ions.

Progress in the crystal growth of Ce : colquiriites

The search for an efficient solid-state laser with tunable emission in the ultraviolet wavelength region has resulted in the growth and development of cerium-doped colquiriite crystals, such as LiCaAlF 6 (LiCAF) and LiSrAlF 6 (LiSAF). Unfortunately, the doping of LiSAF and LiCAF with Ce 3+ introduces different variables into the growth of high optical quality crystals, due to the charge imbalance induced when this trivalent ion substitutes for the divalent site. Charge compensation with Na + tends to produce a more uniformly doped crystal with improved laser properties. Although preliminary research indicated that Ce : LiSAF may be the preferred material of the colquiriite hosts, Ce : LiCAF has also proved to be quite promising.

Divalent effects on cGMP-activated currents in excised patches from amphibian photoreceptors

The light-sensitive current in photoreceptors is conducted by a single class of ion channels gated by the binding of multiple molecules of cytoplasmic cGMP. Both Na and Ca ions enter the outer segment through this channel and Ca behaves as a blocking ion, greatly reducing the influx of Na. Because intracellular Ca functions as the cytosolic messenger for light adaptation, and this channel is the major entry point for Ca into the outer segment, we seek a better understanding of the selectivity properties of the channel and how they affect intracellular Ca levels. In these studies, we added divalent cations to the cytoplasmic face of an excised patch at constant, symmetrical [Na]. Our results suggest a novel high-affinity divalent binding site at the internal face of the channel. At constant low levels of cGMP, the addition of 10-100 nM cytoplasmic Ca or Mg attenuated the current 5- to 10-fold. There is also a low-affinity site, midway through the transmembrane field; saturation of this site reduces the divalent-free current approximately 100-fold. The presence of a high-affinity cytoplasmic site raises the question of whether Ca regulates the photoreceptor current through a direct interaction with the channel perhaps altering the channel selectivity or kinetics.

Quadrupole interactions at divalent and trivalent europium sites in several europium oxides.

The electric-quadrupole interactions at the Eu sites in ${\mathrm{Eu}}_{2}$${\mathrm{CuO}}_{4}$, ${\mathrm{EuBa}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{7\mathrm{\ensuremath{-}}\mathit{x}}$, ${\mathrm{Eu}}_{0.6}$${\mathrm{Sr}}_{0.4}$${\mathrm{VO}}_{2.96}$, ${\mathrm{Eu}}_{3}$${\mathrm{V}}_{2}$${\mathrm{O}}_{7}$, and ${\mathrm{Eu}}_{2}$${\mathrm{VO}}_{4}$ have been studied at room temperature with $^{151}\mathrm{Eu}$ M\"ossbauer spectroscopy. Whereas Eu ions are found to be in trivalent oxidation state in all these oxides, they also occur concurrently in the divalent state in ${\mathrm{Eu}}_{3}$${\mathrm{V}}_{2}$${\mathrm{O}}_{7}$ and ${\mathrm{Eu}}_{2}$${\mathrm{VO}}_{4}$. It is found that the quadrupole coupling constant ${\mathit{eV}}_{\mathit{z}\mathit{z}}$${\mathrm{Q}}_{\mathit{g}}$ is negative in all oxides studied here and in the literature, except ${\mathrm{Eu}}_{2}$${\mathrm{CuO}}_{4}$. This is discussed in terms of different contributions to the electric-field-gradient tensor. The value ${\mathit{eV}}_{\mathit{z}\mathit{z}}$${\mathit{Q}}_{\mathit{g}}$=-18.032(134) mm/s found in ${\mathrm{Eu}}_{2}$${\mathrm{VO}}_{4}$ is, to our knowledge, the largest ever reported for divalent Eu ions on any Eu oxide system.

Sodium‐Calcium exchange: A possible target for drug development

AbstractThe Na+‐Ca2+ exchange system is a carrier‐mediated transport process which couples the transmembrane movement of Ca2+ ions to the movement of Na+ ions in the opposite direction. It functions primarily as a Ca2+ extrusion process in cardiac cells and is thought to be an important mechanism for altering myocardial contractility through changes in intracellular [Na+]. We khave investigated the properties of the cardiac Na+‐Ca2+ exchange system using a subcellular preparation of membrane vesicles derived from the cardiac sarcolemma. Vesicle studies have been useful in investigating the kinetics of Na+‐Ca2+ exchange activity and in establishin the stoichiometry of the exchange process as 3 Na+ per Ca2+. The kinetec results are most easily interpreted in terms of a model for the Na+‐Ca2+ exchange carrier which features two types of cation binding sites: a divalent site for which Ca2+ and 1‐2 Na+ ions compete and a second, monovalent site which binds the third Na+ involved in Na+‐Ca2+ exchange. Na+‐Ca2+ exchange activity in vesicles is stimulated by a variety of agents or treatments, including limited proteolysis, phospholipase treatment, redox reagents, anionic amphiphiles, and intravesicular Ca2+, all of which lower the apparent Km for Ca2+. The physiological significance of these modes of regulation of exchange activity is at present uncertain. Progress in identifying and purifying the exchange carrier has been hampered by the lack of specific high‐affinity probes that could be used in labelling studies. Indirect estimates of the number of exchange carriers in sarcolemmal vesicles suggest that there are 10‐20 pmol of exchanger per mg of membrane protein and that the exchange system has a maximal turnover of approximately 103 sec−1. Studies are under way in several laboratories to clone a cDNA for the exchange carrier using oocytes of Xenopus laevis as an expression system.