Impact of Variations in Water Concentration on the Nanomechanical Behavior of Type I Collagen Microfibrils in Annulus Fibrosus.

Radial variation in water concentration from outer to inner lamellae is one of the characteristic features of annulus fibrosus (AF). In addition, water concentration changes are also associated with intervertebral disc (IVD) degeneration. Such changes alter the chemo-mechanical interactions among the biomolecular constituents at molecular level, affecting the load-bearing nature of IVD. This study investigates mechanistic impacts of water concentration on the collagen type I microfibrils in AF using molecular dynamics simulations. Results show, in axial tension, that increase in water concentration (WC) from 0% to 50% increases the elastic modulus from 2.7 GPa to 3.9 GPa. This is attributed to combination of shift in deformation from backbone straightening to combined backbone stretching- intermolecular sliding and subsequent strengthening of tropocollagen-water (TC-water-TC) interfaces through water bridges and intermolecular electrostatic attractions. Further increase in WC to 75% reduces the modulus to 1.8 GPa due to shift in deformation to polypeptide straightening and weakening of TC-water-TC interface due to reduced electrostatic attraction and increase in the number of water molecules in a water bridge. During axial compression, increase in WC to 50% results in increase in modulus from 0.8 GPa to 4.5 GPa. This is attributed to the combination of the development of hydrostatic pressure and strengthening of the TC-water-TC interface. Further increase in WC to 75% shifts load-bearing characteristic from collagen to water, resulting in a decrease in elastic modulus to 2.8 GPa. Such water-mediated alteration in load-bearing properties acts as foundations toward AF mechanics and provides insights toward understanding degeneration-mediated altered spinal stiffness.

Gas chromatography-electron ionization-mass spectrometry analysis of O,O'- dialkyl methylphosphonites for verification analysis of the Chemical Weapons Convention.

Gas chromatography-mass spectrometry (GC-MS) analysis of O,O'-dialkyl methylphosphonites (DAMPs) was carried out with a view to developing a database and understanding the mechanism of fragmentation. DAMPs are included in the list of schedule 2B4 chemicals of the Chemical Weapons Convention. GC-MS analysis of DAMPs and their deuterated analogs revealed that their fragmentations were dominated by α-cleavages, alkenyl radical loss and hydrogen rearrangements. Based on fragment ions of deuterated analogs and density functional theory calculations, the fragmentation routes were rationalized.

Effect of changes in tropocollagen residue sequence and hydroxyapatite mineral texture on the strength of ideal nanoscale tropocollagen-hydroxyapatite biomaterials.

Changes in mineral texture (e.g. hydroxyapatite (HAP) or aragonite) and polypeptide (e.g. tropocollagen (TC)) residue sequence are characteristic features of a disease known as osteogenesis imperfecta (OI). In OI, different possibilities of changes in polypeptide residue sequence as well as changes in polypeptide helix replacement (e.g. 3 alpha1 chains instead of 2 alpha1 and 1 alpha2 chain in OI murine) exist. The cross section of the HAP crystals could be needle like or plate like. Such texture and residue sequence related changes can significantly affect the material strength at the nanoscale. In this work, a mechanistic understanding of such factors in determining strength of nanoscale TC-HAP biomaterials is presented using three dimensional molecular dynamics (MD) simulations. Analyses point out that the peak interfacial strength for failure is the highest for supercells with plate shaped HAP crystals. TC molecules with higher number of side chain functional groups impart higher strength to the TC-HAP biomaterials at the nanoscale. Overall, HAP crystal shape variation, the direction of applied loading with respect to the relative TC-HAP orientation, and the number of side chain functional groups in TC molecules are the factor that affect TC-HAP biomaterial strength in a significant manner.

Gas chromatography electron ionization mass spectrometric analysis of O-alkyl methylphosphinates for verification of Chemical Weapons Convention.

We describe the gas chromatography/mass spectrometric (GC/MS) analysis of O-alkyl methylphosphinates (AMPs), which are included in schedule 2B4 chemicals in the Chemical Weapons Convention (CWC). GC/MS analysis of variety of AMPs and their deuterated analogues revealed that their fragmentations were determined by alpha-cleavages, McLafferty +1 and hydrogen rearrangements. Based on the obtained electron ionization mass spectra of AMPs the fragmentation routes were rationalized, which were substantiated by the GC/MS analysis of deuterated analogues.

Role of the nanoscale interfacial arrangement in mechanical strength of tropocollagen-hydroxyapatite-based hard biomaterials.

Nanoscale interfacial interactions between a polypeptide (e.g. tropocollagen (TC)) phase and a mineral (e.g. hydroxyapatite (HAP), aragonite) phase is a strong determinant of the strength of hard biological materials such as bone, dentin and nacre. This work presents a mechanistic understanding of such interfacial interactions by examining idealized TC and HAP interfacial systems. For this purpose, three-dimensional molecular dynamics analyses of tensile and compressive failure in two structurally distinct TC-HAP supercells with TC molecules arranged either along or perpendicular to a chosen HAP surface are performed. Analyses point out that the peak interfacial strength for failure results when the load is applied in the direction of TC molecules aligned along the HAP surface such that the contact area between the TC and HAP phases is at a maximum. Such an alignment also leads to the localization of peak stress over a larger length scale resulting in higher fracture strength. The addition of water is found to invariably cause an increase in the mechanical strength. Overall, analyses point out that the relative alignment of TC molecules with respect to the HAP mineral surface such that the contact area is maximal, the optimal direction of applied loading with respect to the TC-HAP orientation and the increase in strength in a hydrated environment can be important factors that contribute to making nanoscale staggered arrangement a preferred structural configuration in biomaterials.

The effect of tensile and compressive loading on the hierarchical strength of idealized tropocollagen-hydroxyapatite biomaterials as a function of the chemical environment.

Hard biomaterials such as bone, dentin and nacre have primarily a polypeptide phase (e.g. tropocollagen (TC)) and a mineral phase (e.g. hydroxyapatite (HAP) or aragonite) arranged in a staggered manner. It has been observed that the mechanical behaviour of such materials changes with the chemical environment and the direction of applied loading. In the presented investigation, explicit three-dimensional molecular dynamics (MD) simulations based analyses are performed on idealized TC-HAP composite biomaterial systems to understand the effects of tensile and compressive loadings in three different chemical environments: (1) unsolvated, (2) solvated with water and (3) calcinated and solvated with water. The MD analyses are performed on two interfacial supercells corresponding to the lowest structural level (level n) of TC-HAP interactions and on two other supercells with HAP supercells arranged in a staggered manner (level n+1) in a TC matrix. The supercells at level n+1 are formed by arranging level n interfacial supercells in a staggered manner. Analyses show that at level n, the presence of water molecules results in greater stability of TC molecules and TC-HAP interfaces during mechanical deformation. In addition, water also acts as a lubricant between adjacent TC molecules. Under the application of shear stress dominated loading, water molecules act to strengthen the TC-HAP interfacial strength in a manner similar to the action of glue. An overall effect of the observed mechanisms is that, in a staggered arrangement, tensile strength increases in the presence of water and calcinated water environments. On the other hand, corresponding compressive strength decreases under similar circumstances. Fundamentally, supercells with primarily normal load transfer at the TC-HAP interfaces are stronger in tensile shear loading. On the other hand, supercells with primarily tangential or shear load transfer at the TC-HAP interfaces are stronger in compressive shear loading. A combination of changes in chemical environment from vacuum to calcinated water and changes in interfacial configurations in a staggered arrangement could be chosen to make the TC-HAP material stronger under applied deformation.

Microsynthesis and gas chromatography/electron ionization mass spectrometric and tandem mass spectrometric analysis of cyclic alkylphosphonates for verification of the Chemical Weapons Convention.

We describe the microsynthesis and gas chromatography/mass spectrometric (GC/MS) analysis of cyclic alkylphosphonates (CAPs), which are included in schedule 2B4 chemicals in the Chemical Weapons Convention (CWC). The reported microsynthesis is efficient in comparison with traditional synthesis. GC/MS and GC/tandem mass spectrometric (MS/MS) analysis of a variety of CAPs revealed that their fragmentations were dominated by alpha-cleavages, alkene eliminations and hydrogen rearrangements. Based on the obtained mass spectra and precursor and product ion analysis of five-, six- and seven-membered cyclic alkylphosphonates, the proposed fragmentation routes rationalize most of the characteristic ions.

Determination of hydrolytic degradation products of nerve agents by injection port fluorination in gas chromatography/mass spectrometry for the verification of the Chemical Weapons Convention.

Retrospective detection and identification of markers of chemical warfare agents are important aspects of verification of the Chemical Weapons Convention. Alkyl alkylphosphonic acids (AAPAs) and alkylphosphonic acids (APAs) are important markers of nerve agents. We describe the development and optimization of a new gas chromatography/mass spectrometry (GC/MS) injection port fluorination method for the derivatization of AAPAs and APAs. The process involved the injection of acids with trifluoroacetic anhydride in GC/MS, where acids are converted into their corresponding volatile fluorides. Various reaction conditions such as fluorinating agent, injection port temperature and splitless time were optimized. The maximum reaction efficiency of the acids with trifluoroacetic anhydride was observed at 230 degrees C injection port temperature with a splitless time of 2 min. APAs showed best analytical efficiencies at 400 degrees C injection port temperature, while the other conditions were similar to those of AAPAs. The linearities of response for APAs and AAPAs were in the range of 1-25 and 5-100 microg mL(-1), respectively, with limits of detection ranging from 500 pg to 800 ng mL(-1).

Gas chromatography/mass spectrometric analysis of N,N-dialkylaminoethyl-2-methoxyethyl ethers as the decontamination markers of N,N-dialkylaminoethyl-2-chlorides for verification of the Chemical Weapons Convention.

The detection and identification of markers of scheduled chemicals plays an important role in verification analysis of Chemical Weapons Convention (CWC). This paper describes the gas chromatography electron ionization mass spectrometric (GC/EI-MS) analysis of N,N-dialkylaminoethyl-2-methoxyethyl ethers (DAEMEs), which are identified as characteristic degradation markers of N,N-dialkylaminoethyl-2-chlorides. N,N-dialkylaminoethyl-2-chlorides produced DAEMEs on reacting with the universally used decontamination solution (DS-2). DAEMEs were prepared by condensation of N,N-dialkylaminoethyl-2-chlorides with 2-methoxy ethanol the active ingredient of DS-2. Based on the GC/EI-MS analysis of DAEMEs the generalized fragmentation routes are proposed which rationalize most of the characteristic ions in EI-MS.

Gas chromatography/mass spectrometric analysis of N,N-dialkylaminoethyl-2-chlorides and trimethylsilyl derivatives of N,N-dialkylaminoethan-2-ols for verification of the Chemical Weapons Convention.

Gas chromatography/electron ionization mass spectrometry (GC/EI-MS) of N,N-dialkylaminoethyl-2-chlorides (DAAECls) and trimethylsilyl (TMS) derivatives of N,N-dialkylaminoethan-2-ols (DAAEAs) has been carried out. GC/EI-MS data of these compounds are of importance for verification of the Chemical Weapons Convention (CWC). Based on these EI mass spectra, generalized fragmentation routes are proposed that rationalize most of the characteristic ions.

Gas chromatography/mass spectrometric analysis of methyl esters of N,N-dialkylaminoethane-2-sulfonic acids for verification of the Chemical Weapons Convention.

This paper describes the synthesis and gas chromatography/electron ionization mass spectrometric (GC/EI-MS) analysis of methyl esters of N,N-dialkylaminoethane-2-sulfonic acids (DAESAs). These sulfonic acids are important environmental signatures of nerve agent VX and its toxic analogues, hence GC/EI-MS analysis of their methyl esters is of paramount importance for verification of the Chemical Weapons Convention. DAESAs were prepared by condensation of 2-bromoethane sulfonic acid with dialkylamines, and by condensation of dialkylaminoethyl chloride with sodium bisulfite. GC/EI-MS analysis of methyl esters of DAESAs yielded mass spectra; based on these spectra, generalized fragmentation routes are proposed that rationalize most of the characteristic ions.