Characterization of currently marketed heparin products: analysis of molecular weight and heparinase-I digest patterns

We evaluated polyacrylamide gel electrophoresis (PAGE) and size exclusion chromatography coupled with multi-angle laser light scattering (SEC-MALLS) approaches to determine weight-average molecular weight (M _w) and polydispersity (PD) of heparins. A set of unfractionated heparin sodium (UFH) and low-molecular-weight heparin (LMWH) samples obtained from nine manufacturers which supply the US market were assessed. For SEC-MALLS, we measured values for water content, refractive index increment (dn/dc), and the second virial coefficient (A ₂) for each sample prior to molecular weight assessment. For UFH, a mean ± standard deviation value for M _w of 16,773 ± 797 was observed with a range of 15,620 to 18,363 (n = 20, run in triplicate). For LMWHs by SEC-MALLS, we measured mean M _w values for dalteparin, tinzaparin, and enoxaparin of 6,717 ± 71 (n = 4), 6,670 ± 417 (n = 3), and 3,959 ± 145 (n = 3), respectively. PAGE analysis of the same UFH, dalteparin, tinzaparin, and enoxaparin samples showed values of 16,135 ± 643 (n = 20), 5,845 ± 45 (n = 4), 6,049 ± 95 (n = 3), and 4,772 ± 69 (n = 3), respectively. These orthogonal measurements are the first M _w results obtained with a large heparin sample set on product being marketed after the heparin crisis of 2008 changed the level of scrutiny of this drug class. In this study, we compare our new data set to samples analyzed over 10 years earlier. In addition, we found that the PAGE analysis of heparinase digested UFH and neat LMWH samples yield characteristic patterns that provide a facile approach for identification and assessment of drug quality and uniformity.     

Predicting the cross-reactivities of polycyclic aromatic hydrocarbons in ELISA by regression analysis and CoMFA methods

Immunoassays have been regarded as a possible alternative or supplement for measuring polycyclic aromatic hydrocarbons (PAHs) in the environment. Since there are too many potential cross-reactants for PAH immunoassays, it is difficult to determine all the cross-reactivities (CRs) by experimental tests. The relationship between CR and the physical-chemical properties of PAHs and related compounds was investigated using the CR data from a commercial enzyme-linked immunosorbent assay (ELISA) kit test. Two quantitative structure-activity relationship (QSAR) techniques, regression analysis and comparative molecular field analysis (CoMFA), were applied for predicting the CR of PAHs in this ELISA kit. Parabolic regression indicates that the CRs are significantly correlated with the logarithm of the partition coefficient for the octanol-water system (log K _ow) (r ² = 0.643, n = 23, P < 0.0001), suggesting that hydrophobic interactions play an important role in the antigen-antibody binding and the cross-reactions in this ELISA test. The CoMFA model obtained shows that the CRs of the PAHs are correlated with the 3D structure of the molecules (r _cv ² = 0.663, r  ² = 0.873, F _4,32 = 55.086). The contributions of the steric and electrostatic fields to CR were 40.4 and 59.6%, respectively. Both of the QSAR models satisfactorily predict the CR in this PAH immunoassay kit, and help in understanding the mechanisms of antigen-antibody interaction.     

Development and validation of an HPLC-UV detection assay for the determination of rufinamide in human plasma and saliva

The development of a simple and rapid high-performance liquid chromatography (HPLC) method for the determination of the new antiepileptic drug rufinamide (RFN) in human plasma and saliva is reported. Samples (250 μl) are alkalinized with ammonium hydroxide (pH 9.25) and extracted with dichloromethane using metoclopramide as internal standard. Separation is achieved with a Spherisorb silica column (250 × 4.6 mm i.d., 5 μm) at 30 °C using as mobile phase a solution of methanol/dichloromethane/n-hexane 10/25/65 (vol/vol/vol) mixed with 6 ml ammonium hydroxide. The instrument used was a Shimadzu LC-10Av chromatograph and flow rate was 1.5 ml min^-1, with a LaChrom L-7400 UV detector set at 230 nm. Calibration curves are linear [r ² = 0.998 ± 0.002 for plasma (n = 10) and r ² = 0.999 ± 0.001 for saliva (n = 9)] over the range of 0.25–20.0 μg ml^-1, with a limit of quantification at 0.25 μg ml^-1. Precision and accuracy are within current acceptability standards. The assay is suitable for pharmacokinetic studies in humans and for therapeutic drug monitoring.     

Characterizing ion mobility-mass spectrometry conformation space for the analysis of complex biological samples

The conformation space occupied by different classes of biomolecules measured by ion mobility-mass spectrometry (IM-MS) is described for utility in the characterization of complex biological samples. Although the qualitative separation of different classes of biomolecules on the basis of structure or collision cross section is known, there is relatively little quantitative cross-section information available for species apart from peptides. In this report, collision cross sections are measured for a large suite of biologically salient species, including oligonucleotides (n = 96), carbohydrates (n = 192), and lipids (n = 53), which are compared to reported values for peptides (n = 610). In general, signals for each class are highly correlated, and at a given mass, these correlations result in predicted collision cross sections that increase in the order oligonucleotides < carbohydrates < peptides < lipids. The specific correlations are described by logarithmic regressions, which best approximate the theoretical trend of increasing collision cross section as a function of increasing mass. A statistical treatment of the signals observed within each molecular class suggests that the breadth of conformation space occupied by each class increases in the order lipids < oligonucleotides < peptides < carbohydrates. The utility of conformation space analysis in the direct analysis of complex biological samples is described, both in the context of qualitative molecular class identification and in fine structure examination within a class. The latter is demonstrated in IM-MS separations of isobaric oligonucleotides, which are interpreted by molecular dynamics simulations. Figure Potential for performing simultaneous “omics” through the separation of biomolecular classes on the basis of structure and mass using ion mobility-mass spectrometry Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.

Octanol/water partitioning simulation by RP‐HPLC for structurally diverse acidic drugs: Comparison of three columns in the presence and absence of n‐octanol as the mobile phase additive

The advantageous effect of n‐octanol as a mobile phase additive for lipophilicity assessment of structurally diverse acidic drugs both in the neutral and ionized form was explored. Two RP C₁₈ columns, ABZ⁺ and Aquasil, were used for the determination of logk_w indices, and the results were compared with those previously reported on a base‐deactivated silica column. At pH 2.5, the use of n‐octanol‐saturated buffer as the mobile phase aqueous component led to high‐quality 1:1 correlation between logk_w and logP for the ABZ⁺ column, while inferior statistics were obtained for Aquasil. At physiological pH, the correlations were significantly improved if strongly ionized acidic drugs were treated separately from weakly ionized ones. In the latter case, 1:1 correlations between logD_7.4 and logk_w^oct indices were obtained in the presence of 0.25% n‐octanol. Concerning strongly ionized compounds, adequate correlations were established under the same conditions; however, slopes were significantly lower than unity, while large negative intercepts were obtained. According to the absolute difference (diff = logD_7.4–logk_w) pattern, base‐deactivated silica showed a better performance than ABZ⁺, however, the latter seems more efficient for the lipophilicity assessment of highly lipophilic acidic compounds. Aquasil may be the column of choice if logD_7.4<3 with the limitation, however, that very hydrophilic compounds cannot be measured.     

SECM visualization of the spatial variability of enzyme-polymer spots. 3. Enzymatic feedback mode

The responses of a PQQ-GDH entrapped in a polymer structure to mixtures of glucose and maltose were evaluated. Each compound was considered in the concentration range of 0–0.2 mM. Imaging was performed at constant height in the enzymatic feedback mode of scanning electrochemical microscopy (SECM). The enzyme-polymer spot was discretized into 15 × 15 μm² substructures which were treated as independent individual microsensors. The response surfaces of the individual microsensors were approximated with a linear regression model. The coefficients in the derived equations represent contributions from topography, glucose concentration, maltose concentration, and the competition of glucose and maltose for the same active site of PQQ-GDH to the measured signal. The ratio of glucose and maltose contributions to the current at the SECM tip was constant for all microsensors and it was predominantly determined by the ratio of the turnover rates of both analytes in the PQQ-GDH catalyzed reaction. Using the difference between these coefficients, it was possible to select the microsensors within the overall enzyme-polymer spot that provided the best data for quantifying glucose and maltose by the artificial neural network used. The quantification of glucose and maltose was successful, except when the contributions from the components of the mixture were n _g =k n units of glucose and simultaneously n _m = 1.86(1−k)n units of maltose, for each constant n > 0 and k∈<0,1>.     

Determination of compound-specific Hg isotope ratios from transient signals using gas chromatography coupled to multicollector inductively coupled plasma mass spectrometry (MC-ICP/MS)

MeHg and inorganic Hg compounds were measured in aqueous media for isotope ratio analysis using aqueous phase derivatization, followed by purge-and-trap preconcentration. Compound-specific isotope ratio measurements were performed by gas chromatography interfaced to MC-ICP/MS. Several methods of calculating isotope ratios were evaluated for their precision and accuracy and compared with conventional continuous flow cold vapor measurements. An apparent fractionation of Hg isotopes was observed during the GC elution process for all isotope pairs, which necessitated integration of signals prior to the isotope ratio calculation. A newly developed average peak ratio method yielded the most accurate isotope ratio in relation to values obtained by a continuous flow technique and the best reproducibility. Compound-specific isotope ratios obtained after GC separation were statistically not different from ratios measured by continuous flow cold vapor measurements. Typical external uncertainties were 0.16‰ RSD (n = 8) for the ²⁰²Hg^/198Hg ratio of MeHg and 0.18‰ RSD for the same ratio in inorganic Hg using the optimized operating conditions. Using a newly developed reference standard addition method, the isotopic composition of inorganic Hg and MeHg synthesized from this inorganic Hg was measured in the same run, obtaining a value of δ ²⁰²Hg = −1.49 ± 0.47 (2SD; n = 10). For optimum performance a minimum mass of 2 ng per Hg species should be introduced onto the column.     

Follow-up of stable isotope analysis of organic versus conventional milk

Analysis of the stable isotope ratio of carbon (δ ¹³C) and α-linolenic acid (C18:3ω3) content in milk fat is a useful indicator of organic milk production. Referring to corresponding measurements, further analyses of stable isotope ratios were performed in 120 samples of conventionally and organically produced whole milk collected from German retailers during a period of 18 months. Conventional milk predominantly exhibited higher δ ¹⁵N values than organic milk, the latter of which never exceeded a maximum δ ¹⁵N threshold value of 5.50‰. Measurements of δ ³⁴S did not differ significantly between organic and conventional milk. Because δ ¹³C, in general, is related to maize consumption, δ ¹³C in milk protein and δ ¹³C in milk fat were equally suited for authentication of organic milk. Thus, a high correlation (r = 0.99) was established between δ ¹³C in milk protein and lipids. Although occurring on different levels in organic and conventional milk, the relatively constant fractionation of carbon isotopes between protein and fat will allow for the advanced detection of adulteration in processed milk products, such as fraudulent combinations of organic milk fat and conventional skim milk. In addition to the strong correlation between C18:3ω3 and δ ¹³C_protein (r = −0.91), a mutual dependence was identified between both δ ¹³C_protein and δ ¹⁵N (r = 0.66) and C18:3ω3 and δ ¹⁵N (r = −0.61). Thus, multi-variable analyses are useful to increase robustness and reduce the number of exceptions in organic milk authentication. Future work involving multivariate statistical analysis can possibly further improve milk authentication in various respects including differentiating between brands of retail milk.     

Topological structures of tetrahedral (Td and T) fullerenes with hexagonal and triangular faces and their vibration and NMR spectra

On analyzing the topological structures of the three types of tetrahedral fullerenes (which consist only of triangles and hexagons), (1) C _n (T _d ,n=12h ²; h=1,2,…), (2) C _n (T _d ,n=4h ²;h=1,2,…), and (3) C _n (T,n=4(h ²+hk+k ²);h>k,h,k=1,2,…), we have obtained theoretically the Infrared and Raman active modes by means of the derived formulas for the decomposition of their nuclear motions into irreducible representations, and the ¹³C NMR spectra with natural abundance for ¹³C by using the distribution functions for all of the tetrahedral (T _d and T) fullerenes, respectively. Received: 25 May 1998 / Accepted: 30 July 1998 / Published online: 23 November 1998     

Sensitive determination of adenine on poly(amidosulfonic acid)-modified glassy carbon electrode

A novel and reliable direct electrochemical method was established for the detection of adenine, based on the differential pulse anodic stripping response at a poly(amidosulfonic acid) (poly-ASA)-modified glassy carbon electrode (GCE) fabricated by electropolymerization. The characterization of electrochemically synthesized poly-ASA film was investigated by atomic force microscopy, electrochemical impedance spectroscopy, and voltammetric methods. This poly-ASA-modified GCE could greatly enhance the detection sensitivity of adenine. At optimum conditions, the anodic peak exhibits a good linear concentration dependence in the range from 3.0 × 10⁻⁸ to 1.0 × 10⁻⁶ M (r = 0.9994). The detection limit is 8.0 × 10⁻⁹ M (S/N = 3). The proposed method could be used to determinate the adenine in tablets of vitamin B₄ with satisfactory results.     

Isokinetic relationships for nucleophilic substitution reactions at the saturated carbon atom. Reactions in aqueous solutions

An isokinetic relationship (IKR) with the parametersT _iso=6145 K and logk _iso=10.622 is valid for nucleophilic substitution reactions at the saturated carbon atom with the participation of anionic nucleophiles in aqueous solutions. The IKR describes the rate constants of the reactions with different anionic nucleophiles, leaving groups, and substituents at the electrophilic reaction center. Similar reactions with neutral nucleophiles, which follow another mechanism, are described by a separate IKR withT _iso=−1232 K and logk _iso=16.226. The reactions of haloforms with hydroxide ion, which proceed by a specific mechanism involving the haloform ionization equilibrium followed by α-elimination of the halide ion, are described by yet another IKR withT _iso=−1463 K and logk _iso=21.057. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 5, pp. 809–814, May, 2000.     

Microgravity experiments on colloidal crystallization of silica spheres in the presence of sodium chloride

 Rate coefficients (k) in the colloidal crystallization of monodispersed silica spheres in the presence of sodium chloride are studied in microgravity achieved by parabolic flights of an aircraft. Time-resolved reflection spectroscopy is made with a continuous circulating-type stopped-flow cell system. The k values decrease as the salt concentration increases both at 0 and 1 G and those in microgravity are smaller than those in normal gravity by 16% (maximum), especially in water and in the presence of a small amount of the salt lower than 2 × 10⁻⁶ mol/l. The rates in flight at 1 G are larger by 15% (maximum) compared with those at 1 G on the ground. The k values obtained at 0 G, 1 G in flight and 1 G on the ground agree excellently with each other for the suspensions with 3 × 10⁻⁶ and 4 × 10⁻⁶ mol/l sodium chloride. Disappearance of the downward diffusion of spheres and no convection of the suspensions are important for retardation in microgravity. Received: 20 January 2000 Accepted: 9 March 2000     

New concept for a toxicity assay based on multiple indexes from the wave shape of damped metabolic oscillation induced in living yeast cells (part I): characterization of the phenomenon

The damped glycolytic oscillation phenomenon occurring in starved cells of the yeast Saccharomyces cerevisiae (NBRC 0565) was characterization for application to a toxicity bioassay. S. cerevisiae was grown under semi-anaerobic conditions. The transient oscillations were observed photometrically as the time course of the fluorescent intensity of reduced pyridine nucleotide resulting from instantaneous addition of glucose to a cell suspension. In this study, simple and reproducible conditions inducing damped oscillations were obtained by modifying a literature method. For estimation of the wave shapes of the damped oscillations we used six indexes. To investigate the total reproducibility as the averaged relative standard deviation (RSD_av) for the six indexes obtained from the wave shapes, the damped oscillations were induced under the optimum conditions and the RSD_av values were calculated as 14% in a buffer cell suspension (n = 62) and 22% in a water cell suspension (n = 78). Finally, the effects of glucose concentration on the six indexes were examined, and all the indexes changed when the glucose concentration was changed. Excellent correlations were obtained between the index of oscillation-state time and the concentration of glucose in a buffer cell suspension (r = 0.9985, 0.5–250 mmol L⁻¹, 10 points) and in a water cell suspension (r = 0.9989, 2.5 μmol L⁻¹–250 mmol L⁻¹, 12 points), respectively. Figure Characterization of damped glycolytic oscillation, (a) typical shape, and (b) its estimation Electronic supplementary material The online version of this article (doi:)contains supplementary material, which is available to authorized users.     

The interaction between sodium dodecylsulfate and the cationic-nonionic random copolymer (3-(2-methylpropionamide)propyl) trimethylammonium chloride–acrylamide of two different charge densities studied using dynamic light scattering and rheometry

The effects of complex formation between sodium dodecylsulfate (SDS) and the positively charged (3-(2-methylpropionamide)propyl)trimethyl-ammonium chloride-acrylamide (MAPTAC-AM) copolymer have been studied in dilute and semidilute aqueous solution in the presence of 10 mM NaCl. Two different charge densities of the copolymer have been used in the study: 0.31 and 0.66, corresponding to the proportion of MAPTAC units. Dynamic light scattering (DLS) and rheometry (static low-shear and capillary viscometry) have been performed on the systems at different charge ratios, i.e., SDS/MAPTAC molar ratios, r. Regarding the phase behavior, the maximum binding ratio prior to precipitation differs between the copolymers. A 1.0% w/v solution of SDS/31% MAPTAC-AM is soluble at r = 0.4 , while an SDS/66% MAPTAC-AM solution of 1.0% w/v shows phase separation at this ratio. With excess surfactant, the complex in the former system is resolubilized at r=2.0, whereas the latter system is still phase-separated at r=5.0. DLS results show that, for both copolymers, the hydrodynamic radius, R _h, of the single-chain copolymer-surfactant complex decreases as a function of r, but then increases slightly prior to phase separation. The corresponding hydrodynamic virial coefficient, k _D, changes in the same manner as R _h. The light-scattering data also show that the formation of larger structures is promoted as the polymer concentration is increased from 0.2 to 1.0% w/v. This is shown by the increase in the relative aggregate-to-single coil peak areas in the relaxation time distributions. Both systems have this common trend. The results from rheological measurements support the results from DLS. A reduction in intrinsic viscosity, [η], is observed on increasing r up to phase separation. The major part of the static low-shear measurements showed Newtonian behavior for both systems at different copolymer concentrations (27.6–138 mM), and at different r. These systems, partially ionic polymer/oppositely charged surfactant, present very interesting rheological behavior at relatively high polymer concentrations and at low r values. Their behavior is similar to those of hydrophobically modified polyelectrolytes. Received: 17 June 1998 Accepted: 12 August 1998     

Development of a highly precise ID-ICP-SFMS method for analysis of low concentrations of lead in rice flour reference materials

Microwave digestion and isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-SFMS) has been applied to the determination of Pb in rice flour. In order to achieve highly precise determination of low concentrations of Pb, the digestion blank for Pb was reduced to 0.21 ng g⁻¹ after optimization of the digestion conditions, in which 20 mL analysis solution was obtained after digestion of 0.5 g rice flour. The observed value of Pb in a non-fat milk powder certified reference material (CRM), NIST SRM 1549, was 16.8 ± 0.8 ng g⁻¹ (mean ± expanded uncertainty, k = 2; n = 5), which agreed with the certified value of 19 ± 3 ng g⁻¹ and indicated the effectiveness of the method. Analytical results for Pb in three brown rice flour CRMs, NIST SRM 1568a, NIES CRM 10-a, and NIES CRM 10-b, were 7.32 ± 0.24 ng g⁻¹ (n = 5), 1010 ± 10 ng g⁻¹ (n = 5), and 1250 ± 20 ng g⁻¹ (n = 5), respectively. The concentration of Pb in a candidate white rice flour reference material (RM) sample prepared by the National Metrology Institute of Japan (NMIJ) was observed to be 4.36 ± 0.28 ng g⁻¹ (n = 10 bottles). Figure Digestion blank of Pb was carefully reduced to approximately 0.2 ng g^-1 which permitted the highly precise determination of Pb at low ng g^-1 level in foodstuff samples by ID-SFMS     

Evaluation of a novel ELISA for serotonin: urinary serotonin as a potential biomarker for depression

Depression is a common disorder with physical and psychological manifestations often associated with low serotonin. Since noninvasive diagnostic tools for depression are sparse, we evaluated the clinical utility of a novel ELISA for the measurement of serotonin in urine from depressed subjects and from subjects under antidepressant therapy. We developed a competitive ELISA for direct measurement of serotonin in derivatized urine samples. Assay performance was evaluated and applied to clinical samples. The analytical range of the assay was from 6.7 to 425 μg serotonin/g creatinine (Cr). The limit of quantification was 4.7 μg/g Cr. The average recovery for spiked urine samples was 104.4%. Average intra-assay variation was 4.4%, and inter-assay variation was <20%. The serotonin analysis was very specific. No significant interferences were observed for 44 structurally and nonstructurally related urinary substances. Very good correlation was observed between urinary serotonin levels measured by ELISA and liquid chromatography tandem mass spectrometry (LC-MS/MS; ELISA = 1.16 × LC-MS/MS − 53.8; r = 0.965; mean % bias = 11%; n = 18). Serotonin was stable in acidified urine for 30 days at room temperature and at −20 °C. The established reference range for serotonin was 54–366 μg/g Cr (n = 64). Serotonin levels detected in depressed patients (87.53 ± 4.89 μg/g Cr; n = 60) were significantly lower (p < 0.001) than in nondepressed subjects (153.38 ± 7.99 μg/g Cr). Urinary excretion of serotonin in depressed individuals significantly increased after antidepressant treatment by 5-hydroxy-tryptophane and/or selective serotonin re-uptake inhibitor (p < 0.01). The present ELISA provides a convenient and robust method for monitoring urinary serotonin. It is suitable to monitor serotonin imbalances and may be particularly helpful in evaluating antidepressant therapies.     

Thermochemistry of Microhydration of Sodiated and Potassiated Monosaccharides

The thermochemical properties ΔH ^o _n , ΔS ^o _n , and ΔG ^o _n for the hydration of sodiated and potassiated monosaccharides (Ara = arabinose, Xyl = xylose, Rib = ribose, Glc = glucose, and Gal = galactose) have been experimentally studied in the gas phase at 10 mbar by equilibria measurements using an electrospray high-pressure mass spectrometer equipped with a pulsed ion beam reaction chamber. The hydration enthalpies for sodiated complexes were found to be between −46.4 and −57.7 kJ/mol for the first, and −42.7 and −52.3 kJ/mol for the second water molecule. For potassiated complexes, the water binding enthalpies were similar for all studied systems and varied between −48.5 and −52.7 kJ/mol. The thermochemical values for each system correspond to a mixture of the α and β anomeric forms of monosaccharide structures involved in their cationized complexes.     

Preparation of micelles with azo dye and UV absorbent at their cores or coronas using non-amphiphilic block copolymers

Micelles with azo dye and UV absorbent at their cores or coronas were prepared from non-amphiphilic random diblock copolymers by α,ω-diamine. Poly[4-(phenylazophenoxymethyl)styrene-ran-4-(2-hydroxybenzophenoxymethyl)styrene-ran-vinylphenol]-block-polystyrene (P(AS-r-HBS-r-VPh)-b-PSt) and poly(vinylphenol)-block-poly[4-(phenylazophenoxymethyl)styrene-ran-4-(2-hydroxybenzophenoxymethyl)styrene-ran-styrene] (PVPh-b-P(AS-r-HBS-r-St)) diblock copolymers were prepared by living radical polymerization mediated by 4-methoxy-2,2,6,6-tetramethylpiperidine-1-oxyl. The former copolymer had a molecular weight of Mn[P(AS-r-HBS-r-VPh)-b-PSt] = 10,000-b-250,000 by ¹H NMR and a molar ratio of AS:HBS:VPh = 0.01:0.01:0.98, while the latter had a molecular weight of Mn[PVPh-b-P(AS-r-HBS-r-St)] = 10,000-b-111,000 and a molar ratio of AS:HBS:St = 0.02:0.03:0.95. The copolymers showed no self-assembly in 1,4-dioxane because this solvent was non-selective to the copolymers. Dynamic light scattering demonstrated that the copolymers formed micelles in the solvent in the presence of α,ω-diamine. The hydrodynamic radii of the micelles slightly increased with the copolymer concentration decrease, while the aggregation numbers were almost independent of the copolymer concentration. It was found that P(AS-r-HBS-r-VPh)-b-PSt formed smaller micelles with a lower aggregation number than PVPh-b-P(AS-r-HBS-r-St) because of the steric hindrance of the AS and HBS units present at the micellar coronas.     

Cage Structure Formation of Singly Doped Aluminum Cluster Cations Al<Subscript><Emphasis Type="BoldItalic">n</Emphasis></Subscript><Emphasis Type="BoldItalic">TM</Emphasis><Superscript>+</Superscript> (<Emphasis Type="BoldItalic">TM</Emphasis> = Ti,V, Cr)

Structural information on free transition metal doped aluminum clusters, Al _n TM ⁺ (TM = Ti, V, Cr), was obtained by studying their ability for argon physisorption. Systematic size (n = 5 – 35) and temperature (T = 145 – 300 K) dependent investigations reveal that bare Al _n ⁺ clusters are inert toward argon, while Al _n TM ⁺ clusters attach one argon atom up to a critical cluster size. This size is interpreted as the geometrical transition from surface-located dopant atoms to endohedrally doped aluminum clusters with the transition metal atom residing in an aluminum cage. The critical size, n _crit , is found to be surprisingly large, namely n _crit = 16 and n _crit = 19 – 21 for TM = V, Cr, and TM = Ti, respectively. Experimental cluster–argon bond dissociation energies have been derived as function of cluster size from equilibrium mass spectra and are in the 0.1–0.3 eV range.