Crystalline Nitridophosphates by Ammonothermal Synthesis

Nitridophosphates are a well‐studied class of compounds with high structural diversity. However, their synthesis is quite challenging, particularly due to the limited thermal stability of starting materials like P3N5. Typically, it requires even high‐pressure techniques (e.g. multianvil) in most cases. Herein, we establish the ammonothermal method as a versatile synthetic tool to access nitridophosphates with different degrees of condensation. α‐Li10P4N10, β‐Li10P4N10, Li18P6N16, Ca2PN3, SrP8N14, and LiPN2 were synthesized in supercritical NH3 at temperatures and pressures up to 1070 K and 200 MPa employing ammonobasic conditions. The products were analyzed by powder X‐ray diffraction, energy dispersive X‐ray spectroscopy, and FTIR spectroscopy. Moreover, we established red phosphorus as a starting material for nitridophosphate synthesis instead of commonly used and not readily available precursors, such as P3N5. This opens a promising preparative access to the emerging compound class of nitridophosphates

HIP to be Square: Simplifying Nitridophosphate Synthesis in a Hot Isostatic Press

(Oxo)Nitridophosphates have recently been identified as a promising compound class for application in the field of solid‐state lighting. Especially, the latest medium‐pressure syntheses under ammonothermal conditions draw attention of the semiconductor and lighting industry on nitridophosphates. In this contribution, we introduce hot isostatic presses as a new type of medium‐pressure synthetic tool, further simplifying nitridophosphate synthesis. In a second step, phosphorus nitride was replaced as starting material by red phosphorus, enabling the synthesis of Ca2PN3 as model compound, starting only from readily available compounds. Moreover, first luminescence investigations on Eu2+‐doped samples reveal Ca2PN3:Eu2+ as a promising broad‐band red‐emitter (λem=650 nm; fwhm=1972 cm−1). Besides simple handling, the presented synthetic method offers access to large sample volumes, and the underlying reaction conditions facilitate single‐crystal growth, required for excellent optical properties

Ammonothermal Synthesis of Ba2PO3N – An Oxonitridophosphate with Non‐Condensed PO3N Tetrahedra

The ortho‐oxonitridophosphate Ba2PO3N was synthesized under ammonobasic conditions (T = 1070 K, p = 120 MPa) in custom‐built high‐temperature autoclaves, starting from red phosphorus, BaO, NaN3 and KOH. Thus, single crystals of up to several hundred µm were obtained, which were used for single‐crystal X‐ray diffraction. Ba2PO3N [Pnma (no. 62), a = 7.596(2), b = 5.796(1), c = 10.212(3) Å, Z = 4] crystallizes in the β‐K2SO4 structure type with non‐condensed [PO3N]4– ions and is isotypic to its lighter homologues EA2PO3N (EA = Ca, Sr). Powder X‐ray diffraction, energy dispersive X‐ray and Fourier Transformed Infrared spectroscopy corroborate the crystal structure. The optical band gap was determined by means of diffuse reflectance UV/Vis spectroscopy to be 4.3 eV. Eu2+ doped samples show green luminescence (λem = 534 nm, fwhm = 85 nm/2961 cm–1) when irradiated with UV light (λexc = 420 nm). However, Ba2PO3N:Eu2+ shows strong thermal quenching, even at room temperature

Sr3P3N7: Complementary Approach by Ammonothermal and High‐Pressure Syntheses

Nitridophosphates exhibit an intriguing structural diversity with different structural motifs, for example, chains, layers or frameworks. In this contribution the novel nitridophosphate Sr3P3N7 with unprecedented dreier double chains is presented. Crystalline powders were synthesized using the ammonothermal method, while single crystals were obtained by a high‐pressure multianvil technique. The crystal structure of Sr3P3N7 was solved and refined from single‐crystal X‐ray diffraction and confirmed by powder X‐ray methods. Sr3P3N7 crystallizes in monoclinic space group P 2/c . Energy‐dispersive X‐ray and Fourier‐transformed infrared spectroscopy were conducted to confirm the chemical composition, as well as the absence of NHx functionality. The optical band gap was estimated to be 4.4 eV using diffuse reflectance UV/Vis spectroscopy. Upon doping with Eu2+, Sr3P3N7 shows a broad deep‐red to infrared emission (λem=681 nm, fwhm≈3402 cm−1) with an internal quantum efficiency of 42 %

PBPK Models for CYP3A4 and P-gp DDI Prediction : A Modeling Network of Rifampicin, Itraconazole, Clarithromycin, Midazolam, Alfentanil, and Digoxin

According to current US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidance documents, physiologically based pharmacokinetic (PBPK) modeling is a powerful tool to explore and quantitatively predict drug-drug interactions (DDIs) and may offer an alternative to dedicated clinical trials. This study provides whole-body PBPK models of rifampicin, itraconazole, clarithromycin, midazolam, alfentanil, and digoxin within the Open Systems Pharmacology (OSP) Suite. All models were built independently, coupled using reported interaction parameters, and mutually evaluated to verify their predictive performance by simulating published clinical DDI studies. In total, 112 studies were used for model development and 57 studies for DDI prediction. 93% of the predicted area under the plasma concentration-time curve (AUC) ratios and 94% of the peak plasma concentration (Cmax) ratios are within twofold of the observed values. This study lays a cornerstone for the qualification of the OSP platform with regard to reliable PBPK predictions of enzyme-mediated and transportermediated DDIs during model-informed drug development. All presented models are provided open-source and transparently documented

Nitride Spinel: An Ultraincompressible High‐Pressure Form of BeP2N4

Owing to its outstanding elastic properties, the nitride spinel γ‐Si3N4 is of considered interest for materials scientists and chemists. DFT calculations suggest that Si3N4‐analog beryllium phosphorus nitride BeP2N4 adopts the spinel structure at elevated pressures as well and shows outstanding elastic properties. Herein, we investigate phenakite‐type BeP2N4 by single‐crystal synchrotron X‐ray diffraction and report the phase transition into the spinel‐type phase at 47 GPa and 1800 K in a laser‐heated diamond anvil cell. The structure of spinel‐type BeP2N4 was refined from pressure‐dependent in situ synchrotron powder X‐ray diffraction measurements down to ambient pressure, which proves spinel‐type BeP2N4 a quenchable and metastable phase at ambient conditions. Its isothermal bulk modulus was determined to 325(8) GPa from equation of state, which indicates that spinel‐type BeP2N4 is an ultraincompressible material

Physiologically Based Pharmacokinetic Models for Prediction of Complex CYP2C8 and OATP1B1 (SLCO1B1) Drug-Drug-Gene Interactions : A Modeling Network of Gemfibrozil, Repaglinide, Pioglitazone, Rifampicin, Clarithromycin and Itraconazole

Background Drug–drug interactions (DDIs) and drug–gene interactions (DGIs) pose a serious health risk that can be avoided by dose adaptation. These interactions are investigated in strictly controlled setups, quantifying the efect of one perpetrator drug or polymorphism at a time, but in real life patients frequently take more than two medications and are very heterogenous regarding their genetic background. Objectives The frst objective of this study was to provide whole-body physiologically based pharmacokinetic (PBPK) models of important cytochrome P450 (CYP) 2C8 perpetrator and victim drugs, built and evaluated for DDI and DGI studies. The second objective was to apply these models to describe complex interactions with more than two interacting partners. Methods PBPK models of the CYP2C8 and organic-anion-transporting polypeptide (OATP) 1B1 perpetrator drug gemfbrozil (parent–metabolite model) and the CYP2C8 victim drugs repaglinide (also an OATP1B1 substrate) and pioglitazone were developed using a total of 103 clinical studies. For evaluation, these models were applied to predict 34 diferent DDI studies, establishing a CYP2C8 and OATP1B1 PBPK DDI modeling network. Results The newly developed models show a good performance, accurately describing plasma concentration–time profles, area under the plasma concentration–time curve (AUC) and maximum plasma concentration (Cmax) values, DDI studies as well as DGI studies. All 34 of the modeled DDI AUC ratios (AUC during DDI/AUC control) and DDI Cmax ratios (Cmax during DDI/Cmax control) are within twofold of the observed values. Conclusions Whole-body PBPK models of gemfbrozil, repaglinide, and pioglitazone have been built and qualifed for DDI and DGI prediction. PBPK modeling is applicable to investigate complex interactions between multiple drugs and genetic polymorphisms

Nitridophosphate‐Based Ultra‐Narrow‐Band Blue‐Emitters: Luminescence Properties of AEP8N14:Eu2+ (AE=Ca, Sr, Ba)

The nitridophosphates AEP8N14 (AE=Ca, Sr, Ba) were synthesized at 4–5 GPa and 1050–1150 °C applying a 1000 t press with multianvil apparatus, following the azide route. The crystal structures of CaP8N14 and SrP8N14 are isotypic. The space group Cmcm was confirmed by powder X‐ray diffraction. The structure of BaP8N14 (space group Amm2) was elucidated by a combination of transmission electron microscopy and diffraction of microfocused synchrotron radiation. Phase purity was confirmed by Rietveld refinement. IR spectra are consistent with the structure models and the chemical compositions were confirmed by X‐ray spectroscopy. Luminescence properties of Eu2+‐doped samples were investigated upon excitation with UV to blue light. CaP8N14 (λem=470 nm; fwhm=1380 cm−1) and SrP8N14 (λem=440 nm; fwhm=1350 cm−1) can be classified as the first ultra‐narrow‐band blue‐emitting Eu2+‐doped nitridophosphates. BaP8N14 shows a notably broader blue emission (λem=417/457 nm; fwhm=2075/3550 cm−1)

Physiologically-Based Pharmacokinetic Models for CYP1A2 Drug-Drug Interaction Prediction: A Modeling Network of Fluvoxamine, Theophylline, Caffeine, Rifampicin, and Midazolam

This study provides whole-body physiologically-based pharmacokinetic models of the strong index cytochrome P450 (CYP)1A2 inhibitor and moderate CYP3A4 inhibitor fluvoxamine and of the sensitive CYP1A2 substrate theophylline. Both models were built and thoroughly evaluated for their application in drug-drug interaction (DDI) prediction in a network of perpetrator and victim drugs, combining them with previously developed models of caffeine (sensitive index CYP1A2 substrate), rifampicin (moderate CYP1A2 inducer), and midazolam (sensitive index CYP3A4 substrate). Simulation of all reported clinical DDI studies for combinations of these five drugs shows that the presented models reliably predict the observed drug concentrations, resulting in seven of eight of the predicted DDI area under the plasma curve (AUC) ratios (AUC during DDI/AUC control) and seven of seven of the predicted DDI peak plasma concentration (Cmax ) ratios (Cmax during DDI/Cmax control) within twofold of the observed values. Therefore, the models are considered qualified for DDI prediction. All models are comprehensively documented and publicly available, as tools to support the drug development and clinical research community