Synthesis and Characterization of Bulky 1,3-Diamidopropane Complexes of Group 2 Metals (Be-Sr).

Reaction of lithium 1,3-diamidopropane Li2(TripNCN) (TripNCN=[{(Trip)NCH2}2CH2]2-, Trip=2,4,6-triisopropylphenyl) with BeBr2(OEt2)2 gave the diamido beryllium complex, [(TripNCN)Be(OEt2)]. Deprotonation reactions between the bulkier 1,3-diaminopropane (TCHPNCN)H2 (TCHPNCN=[{(TCHP)NCH2}2CH2]2-, TCHP=2,4,6-tricyclohexylphenyl) and magnesium alkyls afforded the adduct complexes [(TCHPNCN)Mg(OEt2)] and [(TCHPNCN)Mg(THF)2], depending on the reaction conditions employed. Treating [(TCHPNCN)Mg(THF)2] with the N-heterocyclic carbene :C{(MeNCMe)2} (TMC) gave [(TCHPNCN)Mg(TMC)2] via substitution of the THF ligands. Reactions of (ArNCN)H2 (Ar=Trip or TCHP) with Mg{CH2(SiMe3)}2, in the absence of Lewis bases, yielded the N-bridged dimers [{(ArNCN)Mg}2]. Salt metathesis reactions between alkali metal salts M2(TCHPNCN) (M=Li or K) and CaI2 or SrI2 led to the THF adduct compounds [(TCHPNCN)Ca(THF)3] and [(TCHPNCN)Sr(THF)4], the differing number of THF ligands in which is a result of the different sizes of the metals involved. The described complexes hold potential as precursors to kinetically protected, low oxidation state group 2 metal species.

Evaluation of enzyme activity predictions for variants of unknown significance in Arylsulfatase A.

Continued advances in variant effect prediction are necessary to demonstrate the ability of machine learning methods to accurately determine the clinical impact of variants of unknown significance (VUS). Towards this goal, the ARSA Critical Assessment of Genome Interpretation (CAGI) challenge was designed to characterize progress by utilizing 219 experimentally assayed missense VUS in the Arylsulfatase A (ARSA) gene to assess the performance of community-submitted predictions of variant functional effects. The challenge involved 15 teams, and evaluated additional predictions from established and recently released models. Notably, a model developed by participants of a genetics and coding bootcamp, trained with standard machine-learning tools in Python, demonstrated superior performance among submissions. Furthermore, the study observed that state-of-the-art deep learning methods provided small but statistically significant improvement in predictive performance compared to less elaborate techniques. These findings underscore the utility of variant effect prediction, and the potential for models trained with modest resources to accurately classify VUS in genetic and clinical research.

Low oxidation state and hydrido group 2 complexes: synthesis and applications in the activation of gaseous substrates.

Numerous industrial processes utilise gaseous chemical feedstocks to produce useful chemical products. Atmospheric and other small molecule gases, including anthropogenic waste products (e.g. carbon dioxide), can be viewed as sustainable building blocks to access value-added chemical commodities and materials. While transition metal complexes have been well documented in the reduction and transformation of these substrates, molecular complexes of the terrestrially abundant alkaline earth metals have also demonstrated promise with remarkable reactivity reported towards an array of industrially relevant gases over the past two decades. This review covers low oxidation state and hydrido group 2 complexes and their role in the reduction and transformation of a selection of important gaseous substrates towards value-added chemical products.

Reductions of Arenes using a Magnesium-Dinitrogen Complex.

In this contribution, we present "Birch-type", and other reductions of simple arenes by the potassium salt of an anionic magnesium dinitrogen complex, [{K(TCHPNON)Mg}2(µ-N2)] (TCHPNON=4,5-bis(2,4,6-tricyclohexylanilido)-2,7-diethyl-9,9-dimethyl-xanthene), which acts as a masked dimagnesium(I) diradical in these reactions. This reagent is non-hazardous, easy-to-handle, and in some cases provides access to 1,4-cyclohexadiene reduction products under relatively mild reaction conditions. This system works effectively to reduce benzene, naphthalene and anthracene through magnesium-bound "Birch-type" reduction intermediates. Cyclohexadiene products can be subsequently released from the magnesium centres by protonolysis with methanol. In contrast, the reduction of substituted arenes is less selective and involves competing reaction pathways. For toluene and 1,3,5-triphenylbenzene, the structural authentication of "Birch-type" reduction intermediates is conclusive, although the formation of corresponding 1,4-cyclohexadiene derivatives was low yielding. Reduction of anisole did not yield an isolable "Birch-type" intermediate, but instead gave a C-O activation product. Treating triphenylphosphine with [{K(TCHPNON)Mg}2(µ-N2)] resulted in the extrusion of both biphenyl and dinitrogen to afford a magnesium(II) phosphanide [{K(TCHPNON)Mg(µ-PPh2)}2]. Reduction of fluorobenzene proceeded via C-F activation of the arene, and isolation of the magnesium(II) fluoride [{K(TCHPNON)Mg(µ-F)}2]. Finally, the two-electron reduction of 1,3,5,7-cyclooctatetraene (COT) with [{K(TCHPNON)Mg}2(µ-N2)] yielded a complex, [{K(TCHPNON)Mg}2(µ-COT)], incorporating the aromatic dianion (COT2-).

Enforcing Metal-Arene Interactions in Bulky p-Terphenyl Bis(anilide) Complexes of Group 2 Metals (Be-Ba): Potential Precursors for Low-Oxidation-State Alkaline Earth Metal Systems.

An extremely bulky p-terphenyl bis(aniline), p-C6H4{C6H4[N(H)TCHP]-2}2 (TCHP = 2,4,6-tricyclohexylphenyl) TCHPTerphH2, has been developed. Deprotonation of a less bulky analogue, DipTerphH2 (Dip = 2,6-diisopropylphenyl), with BePh2 affords the bimetallic system, [(BePh)2(µ-DipTerph)] 1. Treating either TCHPTerphH2 or DipTerphH2 with Mg{CH2(SiMe3)}2 gives the monomeric bis(anilide) complexes [Mg(ArTerph)] (Ar = Dip 2, TCHP 3) which display rare examples of η6-arene coordination to the metal center. Treating 2 with THF leads to partial dissociation of the Mg···arene interaction and formation of [Mg(DipTerph)(THF)] 4. Reactions of the bis(aniline)s with the group 2 metal amides [M{N(SiMe3)2}2] afford dimeric, structurally analogous compounds [{M(ArTerph)}2] (Ar = Dip, M = Ca 5, Sr 6, Ba 7; Ar = TCHP, M = Ca 8, Sr 9, Ba 10) which display intermolecular M···arene interactions in the solid state. Computational studies have shown that the intramolecular M···Î·6-arene interactions in models of the ether-free metal bis(anilide) compounds are largely electrostatic in nature. Reductions of these compounds with alkali metals led to mixtures of unidentified products.

Synthesis and Reactivity of Discrete Europium(II) Hydride Complexes.

The bulky ß-diketiminate ligand frameworks [BDIDCHP]- and [BDIDipp/Ar]- (BDI=[HC{C(Me)2N-Dipp/Ar}2]- (Dipp=2,6-diisopropylphenyl (Dipp); Ar=2,6-dicyclohexylphyenyl (DCHP) or 2,4,6-tricyclohexylphyenyl (TCHP)) have been developed for the kinetic stabilisation of the first europium (II) hydride complexes, [(BDIDCHP)Eu(µ-H)]2, [(BDIDipp/DCHP)Eu(µ-H)]2 and [(BDIDipp/TCHP)Eu(µ-H)]2, respectively. These complexes represent the first step beyond the current lanthanide(II) hydrides that are all based on ytterbium. Tuning the steric profile of ß-diketiminate ligands from a symmetrical to unsymmetrical disposition, enhanced solubility and stability in the solution-state. This provides the first opportunity to study the structure and bonding of these novel Eu(II) hydride complexes crystallographically, spectroscopically and computationally, with their preliminary reactivity investigated.

A bromo(boryloxy) silylene and its heavier analogues.

A N-heterocylic boryloxy ligand equipped with bulky diazaboryl N-substituents is used to synthesize divalent and dicoordinate group 14 compounds which represent the first examples of acyclic halo(boryloxy) tetrylenes. The bromo(boryloxy) silylene reacts swiftly with benzophenone to a siloxindane.

Steric control of Mg-Mg bond formation vs. N2 activation in the reduction of bulky magnesium diamide complexes.

Reduction of the magnesium(II) diamide [Mg(TripNON)] (TripNON = 4,5-bis(2,4,6-triisopropylanilido)-2,7-diethyl-9,9-dimethyl-xanthene) with 5% w/w K/KI leads to a good yield of a dianionic dimagnesium(I) species, as its potassium salt, [{K(TripNON)Mg}2]. An X-ray crystallographic analysis shows the molecule to contain a very long Mg-Mg bond (3.137(2) Å). The formation of [{K(TripNON)Mg}2] contrasts with a previously reported reduction of a magnesium(II) complex incorporating a bulkier diamide ligand, which instead afforded a magnesium-dinitrogen complex. In the current study, [{K(TripNON)Mg}2] has been shown to be a viable reagent for the reductive activation of CO, H2 and N2O.

Reductive Metallation of Dendralenes and Myrcene Using Dimagnesium(I) Compounds: A Facile Route to Unsaturated Organomagnesium Compounds.

The two-electron reduction of 2,3-dimethylbuta-1,3-diene (DMB) with ß-diketiminate and guanidinate substituted dimagnesium(I) compounds has given complexes in which two bidentate amido-magnesium fragments are bridged through the π-system of the DMB dianion, viz. [(LMg)2 (µ-DMB)] (L=Xyl Nacnac, [HC(MeCNXyl)2 ]- , Xyl=2,6-xylyl; or Priso=[(DipN)2 CNPri 2 ]- , Dip=2,6-diisopropylphenyl). Similar double reductions of [4]dendralene (4dend) have afforded the complexes, [(LMg)2 (µ-4dend)] (L=Ar Nacnac, Ar=Xyl or mesityl (Mes); or Priso) in which the 4dend dianion is π-coordinated to the bidentate amido-magnesium fragments. Treatment of several such complexes with THF leads to Z- to E-isomerization of the dendralene fragment, and formation of purely σ-bonded Mg-C interactions in the THF coordinated products [{(Ar Nacnac)(THF)Mg}2 (µ-4dend)] (Ar=Xyl, Mes or Dip). Reaction of myrcene (Myr) with [{(Xyl Nacnac)Mg}2 ] proceeds via reductive coupling of Myr to give a previously unknown acyclic, branched C20 tetra-olefin dianion complex [{(Xyl Nacnac)(THF)Mg}2 (µ-Myr)2 ]. Preliminary reactions of [(LMg)2 (µ-DMB)] with H2 and/or CO yielded a series of products, including novel magnesium hydride compounds, products derived from couplings of CO with the reduced DMB fragment (viz. magnesium dimethylcyclohexadienediolates), and one magnesium cyclopropanetriolate complex from the magnesium(I) induced coupling of DMB with H2 and CO.

Stabilization and One Electron Reduction of a Silicon Analogue of a Carboxylic Acid Anhydride.

Reaction of the 1,2-disilylenes {(DipAr Am)Si}2 (DipAr Am=[(NDip)2 CAr]- , Dip=2,6-diisopropylphenyl, Ar=4-C6 H4 But (Ar') 1 a or Ph 1 b) and two abnormal N-heterocyclic silylenes, (DipAr Am)SiOCSi{(NDip)2 CAr} (Ar=Ar' 3 a or Ph 3 b) with N2 O led to formation of unprecedented examples of uncoordinated silicon analogues of carboxylic acid anhydrides, (DipAr Am)(O=)SiOSi(=O)(DipAr Am) (Ar=Ar' 2 a or Ph 2 b). Both compounds have been fully characterized, and the mechanism of formation of one explored using DFT calculations. Reduction of sila-acid anhydride 2 a with a dimagnesium(I) compound, [{(Mes Nacnac)Mg}2 ] (Mes Nacnac=[(MesNCMe)2 CH]- , Mes=mesityl), led to the one-electron reduction of the anhydride and formation of a magnesium complex of a sila-acid anhydride radical anion [(Mes Nacnac)Mg{(OSi(DipAr' Am)}2 O] 5. A combination of EPR spectroscopic studies and DFT calculations reveal the unpaired electron to largely reside on one of the amidinate ligands of the complex.

Factors Associated with Interviewers' Evaluations of Respondents' Performance in Telephone Interviews: Behavior, Response Quality Indicators, and Characteristics of Respondents and Interviewers.

Interviewers' postinterview evaluations of respondents' performance (IEPs) are paradata, used to describe the quality of the data obtained from respondents. IEPs are driven by a combination of factors, including respondents' and interviewers' sociodemographic characteristics and what actually transpires during the interview. However, relatively few studies examine how IEPs are associated with features of the response process, including facets of the interviewer-respondent interaction and patterns of responding that index data quality. We examine whether features of the response process-various respondents' behaviors and response quality indicators-are associated with IEPs in a survey with a diverse set of respondents focused on barriers and facilitators to participating in medical research. We also examine whether there are differences in IEPs across respondents' and interviewers' sociodemographic characteristics. Our results show that both respondents' behaviors and response quality indicators predict IEPs, indicating that IEPs reflect what transpires in the interview. In addition, interviewers appear to approach the task of evaluating respondents with differing frameworks, as evidenced by the variation in IEPs attributable to interviewers and associations between IEPs and interviewers' gender. Further, IEPs were associated with respondents' education and ethnoracial identity, net of respondents' behaviors, response quality indicators, and sociodemographic characteristics of respondents and interviewers. Future research should continue to build on studies that examine the correlates of IEPs to better inform whether, when, and how to use IEPs as paradata about the quality of the data obtained.

A Multipronged Intervention to Reduce Readmissions and Readmission Intensity After Radical Cystectomy.

OBJECTIVE: To develop a multipronged, evidence-based protocol to reduce readmission risk and readmission intensity, as represented by the duration of the index readmission, after radical cystectomy. MATERIALS AND METHODS: A per-protocol study was performed. The protocol included preoperative nutritional supplementation, early stent removal, and a follow-up phone call within 4-5days of discharge. The preprotocol period was from February 1, 2020 to July 31, 2021 and the postprotocol period was from December 1, 2020 to November 31, 2021. Using multivariate regression models, we compared outcomes among patients treated with radical cystectomy before and after protocol initiation. RESULTS: We identified 70 preprotocol patients and 126 postprotocol patients. After adjusting for age, sex, BMI, and frailty score, there was a significant reduction in 90-day readmission intensity (7 vs 5days; P = .048) among postprotocol patients. CONCLUSION: After implementation of an evidence-based protocol for patients undergoing radical 90-day readmission intensity decreased significantly. This protocol may move the needle forward on reducing readmissions, but a larger randomized trial is needed.

Synthesis and Reactivity of Alkali Metal Hydrido-Magnesiate Complexes which Exhibit Group 1 Metal Counter-Cation Specific Stability.

Reactions of the series of alkali metal amides M(HMDS) (M = Li-Cs; HMDS = [N(SiMe3)2]-) with the neutral magnesium(II) hydride compound [Mg(BDIDipp)(µ-H)]2 (BDIDipp = [CH{C(Me)NDipp}2], Dipp = 2,6-iPr2-C6H3) have been carried out. When M = Li or Na, the reactions yielded Mg(BDIDipp)(HMDS) and MH as the primary products. In the sodium amide reaction, [Na2(HMDS)][{Mg(BDIDipp)}2(H)3] was obtained as a low-yield by-product. When M = K-Cs, the reactions gave the group 1 metal hydrido-magnesiates, M2[Mg(BDIDipp)(HMDS)(H)]2·(benzene)n (n = 0 or 1), the thermal stability of which increases with the increasing molecular weight of the alkali metal involved. Reactions of Cs2[Mg(BDIDipp)(HMDS)(H)]2·(benzene) with 18-crown-6 and CO gave the first monomeric alkali metal hydrido-magnesiate [Cs(18-crown-6)][Mg(BDIDipp)(HMDS)(H)] and the ethenediolate complex Cs2[{Mg(BDIDipp)(HMDS)}2(µ-C2H2O2)], respectively. The new synthetic route to alkali metal hydrido-magnesiates described herein may facilitate further reactivity studies of this rare compound class.

Schlenk-Type Equilibria of Grignard-Analogous Arylberyllium Complexes: Steric Effects.

The presence of complex Schlenk equilibria is a central property of synthetically invaluable Grignard reagents substantially affecting their reactivity and selectivity in chemical transformations. In this work, the steric effects of aryl substituents on the Schlenk-type equilibria of their lighter congeners, arylberyllium bromides, are systematically studied. Combination of diarylberyllium complexes Ar2 Be(OEt2 ) (1Ar, Ar=Tip, Tcpp; Tip=2,4,6-iPr3 C6 H3 , Tcpp=2,4,6-Cyp3 C6 H3 , Cyp=c-C5 H9 ), containing sterically demanding aryl groups, and BeBr2 (OEt2 )2 (2) affords the Grignard-analogous arylberyllium bromides ArBeBr(OEt2 ) (3Ar, Ar=Tip, Tcpp). In contrast, Mes2 Be(OEt2 ) (1Mes, Mes=2,4,6-Me3 C6 H3 ) and 2 exist in a temperature-dependent equilibrium with MesBeBr(OEt2 ) (3Mes) and free OEt2 . Ph2 Be(OEt2 ) (1Ph) reacts with 2 to afford dimeric [PhBeBr(OEt2 )]2 ([3Ph]2 ). Moreover, the influence of replacing the OEt2 donor by an N-heterocyclic carbene, IPr2 Me2 (IPr2 Me2 =C(iPrNCMe)2 ), on the redistribution reactions was investigated. The solution- and solid-state structures of the diarylberyllium and arylberyllium bromide complexes were comprehensively characterized using multinuclear (1 H, 9 Be, 13 C) NMR spectroscopic methods and single-crystal X-ray diffraction, while DFT calculations were employed to support the experimental findings.

Coordination and Activation of N2 at Low-Valent Magnesium using a Heterobimetallic Approach: Synthesis and Reactivity of a Masked Dimagnesium Diradical.

The activation of dinitrogen (N2 ) by transition metals is central to the highly energy intensive, heterogeneous Haber-Bosch process. Considerable progress has been made towards more sustainable homogeneous activations of N2 with d- and f-block metals, though little success has been had with main group metals. Here we report that the reduction of a bulky magnesium(II) amide [(TCHP NON)Mg] (TCHP NON=4,5-bis(2,4,6-tricyclohexylanilido)-2,7-diethyl-9,9-dimethyl-xanthene) with 5 % w/w K/KI yields the magnesium-N2 complex [{K(TCHP NON)Mg}2 (µ-N2 )]. DFT calculations and experimental data show that the dinitrogen unit in the complex has been reduced to the N2 2- dianion, via a transient anionic magnesium(I) radical. The compound readily reductively activates CO, H2 and C2 H4 , in reactions in which it acts as a masked dimagnesium(I) diradical.

Do Large Language Models Know What Humans Know?

Humans can attribute beliefs to others. However, it is unknown to what extent this ability results from an innate biological endowment or from experience accrued through child development, particularly exposure to language describing others' mental states. We test the viability of the language exposure hypothesis by assessing whether models exposed to large quantities of human language display sensitivity to the implied knowledge states of characters in written passages. In pre-registered analyses, we present a linguistic version of the False Belief Task to both human participants and a large language model, GPT-3. Both are sensitive to others' beliefs, but while the language model significantly exceeds chance behavior, it does not perform as well as the humans nor does it explain the full extent of their behavior-despite being exposed to more language than a human would in a lifetime. This suggests that while statistical learning from language exposure may in part explain how humans develop the ability to reason about the mental states of others, other mechanisms are also responsible.

Regenerative Engineering of a Biphasic Patient-Fitted Temporomandibular Joint Condylar Prosthesis.

Regenerative medicine approaches to restore the mandibular condyle of the temporomandibular joint (TMJ) may fill an unmet patient need. In this study, a method to implant an acellular regenerative TMJ prosthesis was developed for orthotopic implantation in a pilot goat study. The scaffold incorporated a porous, polycaprolactone-hydroxyapatite (PCL-HAp, 20wt% HAp) 3D printed condyle with a cartilage-matrix-containing hydrogel. A series of material characterizations was used to determine the structure, fluid transport, and mechanical properties of 3D printed PCL-HAp. To promote marrow uptake for cell seeding, a scaffold pore size of 152 ± 68 µm resulted in a whole blood transport initial velocity of 3.7 ± 1.2 mm·s-1 transported to the full 1 cm height. The Young's modulus of PCL was increased by 67% with the addition of HAp, resulting in a stiffness of 269 ± 20 MPa for etched PCL-HAp. In addition, the bending modulus increased by 2.06-fold with the addition of HAp to 470 MPa for PCL-HAp. The prosthesis design with an integrated hydrogel was compared with unoperated contralateral control and no-hydrogel group in a goat model for 6 months. A guide was used to make the condylectomy cut, and the TMJ disc was preserved. MicroCT assessment of bone suggested variable tissue responses with some regions of bone growth and loss, although more loss may have been exhibited by the hydrogel group than the no-hydrogel group. A benchtop load transmission test suggested that the prosthesis was not shielding load to the underlying bone. Although variable, signs of neocartilage formation were exhibited by Alcian blue and collagen II staining on the anterior, functional surface of the condyle. Overall, this study demonstrated signs of functional TMJ restoration with an acellular prosthesis. There were apparent limitations to continuous, reproducible bone formation, and stratified zonal cartilage regeneration. Future work may refine the prosthesis design for a regenerative TMJ prosthesis amenable to clinical translation.

Molybdenum carbonyl assisted reductive tetramerization of CO by activated magnesium(i) compounds: squarate dianion vs. metallo-ketene formation.

Reactions of a dimagnesium(i) compound, [{(DipNacnac)Mg}2] (DipNacnac = [HC(MeCNDip)2]-, Dip = 2,6-diisopropylphenyl), pre-activated by coordination with simple Lewis bases (4-dimethylaminopyridine, DMAP; or TMC, :C(MeNCMe)2), with 1 atmosphere of CO in the presence of one equivalent of Mo(CO)6 at room temperature, led to the reductive tetramerisation of the diatomic molecule. When the reactions were carried out at room temperature, there is an apparent competition between the formation of magnesium squarate, [{(DipNacnac)Mg}{cyclo-(κ4-C4O4)}{µ-Mg(DipNacnac)}]2, and magnesium metallo-ketene products, [{(DipNacnac)Mg}[µ-O[double bond, length as m-dash]CC{Mo(CO)5}C(O)CO2]{Mg(D)(DipNacnac)}], which are not inter-convertible. Repeating the reactions at 80 °C led to the selective formation of the magnesium squarate, implying that this is the thermodynamic product. In an analogous reaction, in which THF is the Lewis base, only the metallo-ketene complex, [{(DipNacnac)Mg}[µ-O[double bond, length as m-dash]CC{Mo(CO)5}C(O)CO2]{Mg(THF)(DipNacnac)}] is formed at room temperature, while a complex product mixture is obtained at elevated temperature. In contrast, treatment of a 1 : 1 mixture of the guanidinato magnesium(i) complex, [(Priso)Mg-Mg(Priso)] (Priso = [Pri2NC(NDip)2]-), and Mo(CO)6, with CO gas in a benzene/THF solution, gave a low yield of the squarate complex, [{(Priso)(THF)Mg}{cyclo-(κ4-C4O4)}{µ-Mg(THF)(Priso)}]2, at 80 °C. Computational analyses of the electronic structure of squarate and metallo-ketene product types corroborate the bonding proposed from experimental data, for the C4O4 fragments of these systems.

Magnesium(I) Reduction of Aluminum(III) Hydride Complexes: Generation of Mixed Valence Aluminum (AlI /Al0 ) Hydride Cluster Compounds, [Al6 H8 (NR3 )2 {Mg(ß-diketiminate)}4 ].

Reduction of a range of amido- and aryloxy-aluminum dihydride complexes, e.g. [AlH2 (NR3 ){N(SiMe3 )2 }] (NR3 =NMe3 or N-methylpiperidine (NMP)), with ß-diketiminato dimagnesium(I) reagents, [{(Ar Nacnac)Mg}2 ] (Ar Nacnac=[HC(MeCNAr)2 ]- , Ar=mesityl (Mes) or 2,6-xylyl (Xyl)), have afforded deep red mixed valence aluminum hydride cluster compounds, [Al6 H8 (NR3 )2 {Mg(Ar Nacnac)}4 ], which have an average Al oxidation state of +0.66, the lowest for any well-defined aluminum hydride compound. In the solid-state, the clusters are shown to have distorted octahedral Al6 cores, having zero-valent Al axial sites and mono-valent AlH2 - equatorial units. Several novel by-products were isolated from the reactions that gave the clusters, including the Mg-Al bonded magnesio-aluminate complexes, [(Ar Nacnac)(Me3 N)Mg-Al(µ-H)3 [{Mg(Ar Nacnac)}2 (µ-H)]]. Computational analyses of one aluminum hydride cluster revealed its Al6 core to be electronically delocalized, and to possess one unoccupied, and six occupied, skeletal molecular orbitals.

Preparative Electrophoresis for HDL Particle Size Separation and Intact-Mass Apolipoprotein Proteoform Analysis.

The most abundant proteins on high-density lipoproteins (HDLs), apolipoproteins A-I (APOA1) and A-II (APOA2), are determinants of HDL function with 15 and 9 proteoforms (chemical-structure variants), respectively. The relative abundance of these proteoforms in human serum is associated with HDL cholesterol efflux capacity, and cholesterol content. However, the association between proteoform concentrations and HDL size is unknown. We employed a novel native-gel electrophoresis technique, clear native gel-eluted liquid fraction entrapment electrophoresis (CN-GELFrEE) paired with mass spectrometry of intact proteins to investigate this association. Pooled serum was fractionated using acrylamide gels of lengths 8 and 25 cm. Western blotting determined molecular diameter and intact-mass spectrometry determined proteoform profiles of each fraction. The 8- and 25 cm experiments generated 19 and 36 differently sized HDL fractions, respectively. The proteoform distribution varied across size. Fatty-acylated APOA1 proteoforms were associated with larger HDL sizes (Pearson's R = 0.94, p = 4 × 10-7) and were approximately four times more abundant in particles larger than 9.6 nm than in total serum; HDL-unbound APOA1 was acylation-free and contained the pro-peptide proAPOA1. APOA2 proteoform abundance was similar across HDL sizes. Our results establish CN-GELFrEE as an effective lipid-particle separation technique and suggest that acylated proteoforms of APOA1 are associated with larger HDL particles.