# Evidence: halogen bonding

Parent: — · class: molecular interaction · names merged here: halogen bonding

4 papers measured or used it, 3 only mentioned it (of 207 kept papers). Papers in year order; each section heading ends with the paper's category / subcategory. Generated by tools/build_evidence.py from registry/concepts.csv and the cards; do not edit.

## 2020 Que — Evidence for Halogen Bonding in Amorphous Solid Dispersions · Solid state stability / Miscibility and drug-polymer interactions

[2020-que-halogen-bonding-amorphous-solid-dispersions](../../../cards/2020-que-halogen-bonding-amorphous-solid-dispersions/paper.html) · Solid state stability / Miscibility and drug-polymer interactions · measured · as: halogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R7 | record, measured | halogen core-level BE, neat compound and new low-BE peaks in polymer — P5; ASDs (P4); DL and n behind each value not stated — sub-table R7 | Table 1, p. 18; p. 15 |
| R9 | record, measured | percentage of halogen atoms with lower BE vs DL — P5; ASDs (P4) — sub-table R9; Fig. 3 bars (high-BE share ≈ 100 minus each value) agree with Table S2 | Table S2, SI p. 9; Fig. 3, pp. 19-21; p. 18 |
| R10 | record, measured | O 1s BE of PVP carbonyl — neat PVP vs clotrimazole/PVP 50/50 wt% (P5) — text: O 1s shifted to higher BE by 0.2 eV in the dispersion; peak maxima ≈530.8 eV (PVP) and ≈531.0 eV (dispersion), peak heights ≈1400 and ≈2300 CPS (read from Fig. 6S) | p. 28; Fig. 6S, SI p. 10 |
| R11 | record, measured | IR carbonyl band positions — P7 films; 10-90% DL — pure PVPVA: VP C=O "around" 1684 cm-1, VA C=O 1736 cm-1; clotrimazole-PVPVA and brotrimazole-PVPVA: VP C=O maximum 1684 → 1682 cm-1 from 10% to 90% DL, VA C=O position unchanged; Me-DIBF-PVPVA: VP C=O downshift 6 cm-1; Me-DIBF films: absorbance above ≈1750 cm-1 rises with DL and the 90% VP band is broader (read from Fig. 5c) | p. 25; Fig. 5, pp. 25-26 |
| R12 | record, measured | KF with EP in cyclohexane — P6; 25 °C; n = 3 titrations — sub-table R12 | Table 2, p. 24 |
| C1 | claim, conclusion, authors: abstract: asserted ("demonstrated"); p. 27: asserted ("compelling evidence"); p. 28: "we propose"; p. 31: asserted ("were found") | On the combined XPS, NMR and IR evidence, the four model compounds (Cl, Br, I; no H-bond donors) are proposed to form halogen bonds with the amide carbonyl of the VP unit of PVPVA (and of PVP for clotrimazole) in the ASDs [rests on: R7, R8, R9, R10, R11, R12, R14, R15, R16] | pp. 2, 6, 27-28, 31 |

## 2021 Que — Impact of Drug−Polymer Intermolecular Interactions on Dissolution Performance of Copovidone-Based Amorphous Solid Dispersions · Dissolution / A. Release mechanism and LoC

[2021-que-drug-polymer-interactions-loc-copovidone-asd](../../../cards/2021-que-drug-polymer-interactions-loc-copovidone-asd/paper.html) · Dissolution / A. Release mechanism and LoC · measured · as: halogen bonding

| id | kind | content | locator |
|---|---|---|---|
| R9 | record, measured | I 3d binding energies (P3) — neat amorphous compounds (as printed) and TIPP/PVPVA, Me-TIPP/PVPVA ASD compacts — neat: one doublet, 620.7 ± 0.01 eV (I 3d5/2) and 632.2 ± 0.04 eV (printed "I 3d1/2"); ASDs: additional doublet at lower BE, 618.1 ± 0.05 and 629.6 ± 0.05 eV; doublet components in ratio 3:2 | Section 4.2.2, p.3501; SI Fig. 4S |
| R11 | record, measured (TIPP); cited ref 17 per Section 3.3 (Me-TIPP) | atomic percentage of I atoms at the lower BE (mean ± STDEV) — ASD compacts, 10−40% DL — see sub-table R11 | SI Table 1S, SI pdf p.5; p.3501 |
| R12 | record, derived (E4) | molar amount of lower-BE I atoms in 100 mg ASD (mmol) — ASD compacts, 10−40% DL — see sub-table R12 (read from Fig. 3) | Fig. 3, p.3501 |
| C7 | claim, conclusion, authors: results: asserted ("can only form"); discussion: "suggesting" | Me-TIPP can form only halogen bonds with VP carbonyls, and its smaller VP shift suggests this halogen bond is weaker than the hydrogen bond formed by the phenolic group. [rests on: R7, R9] | Section 4.2.1, p.3500; Section 5, p.3503 |
| C15 | claim, conclusion, authors: "suggests"; "likely"; discussion: "is supported by" | The lower-BE I 3d doublet suggests a portion of I atoms became more electron-rich, likely through I···O=C (VP) halogen bonding after dispersion in the polymer; this supports attributing the Me-TIPP IR shift to halogen bonding. [rests on: R9, R10, R11] | Section 4.2.2, p.3501; Section 5, p.3503 |

## 2023 Deac — Dissolution Mechanisms of Amorphous Solid Dispersions: Role of Drug Load and Molecular Interactions · Dissolution / A. Release mechanism and LoC

[2023-deac-asd-drug-load-molecular-interactions-loc](../../../cards/2023-deac-asd-drug-load-molecular-interactions-loc/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: halogen bonding

| id | kind | content | locator |
|---|---|---|---|
| C2 | claim, prior hypothesis, authors: asserted ("As demonstrated by spectroscopic methods") | The LoC correlates with drug-polymer interaction strength, lower for stronger interactions: for the four analogues (PHPH hydrogen bonds, TIPP hydrogen and halogen bonds, MeTIPP halogen bonds, MePHPH none) hydrogen-bonding systems had significantly lower LoCs, the LoC falling with the cumulative strength/extent of specific interactions; indomethacin versus its ester showed the same in PVPVA [rests on: cited: refs 14, 31, 34; R8, R17] | p.722, p.724, p.729 |
| M2 | material | TIPP (3′,3″,5′,5″-tetraiodophenolphthalein) purchased from Sigma-Aldrich; two OH groups and four iodine atoms (Fig. 1c) | p.723, p.724 |
| M3 | material | MeTIPP (3,3-bis(3,5-diiodo-4-methoxyphenyl)isobenzofuran-1(3H)-one) synthesized as described in ref 14; two methoxy groups and four iodine atoms (Fig. 1d) | p.723, p.724 |

## 2024 Deac — Dissolution Mechanisms of Amorphous Solid Dispersions: Application of Ternary Phase Diagrams To Explain Release Behavior · Dissolution / A. Release mechanism and LoC

[2024-deac-asd-ternary-phase-diagrams-release](../../../cards/2024-deac-asd-ternary-phase-diagrams-release/paper.html) · Dissolution / A. Release mechanism and LoC · used · as: halogen bonding

| id | kind | content | locator |
|---|---|---|---|
| P19 | method | PC-SAFT phase diagram calculation | p.1905; SI p.14, p.19-22 |

## Mentioned only

- 2019 Que — [2019-que-ledipasvir-copovidone-asd-loc-interactions](../../../cards/2019-que-ledipasvir-copovidone-asd-loc-interactions/paper.html) · Dissolution / A. Release mechanism and LoC (ref C27)
- 2021 Yang — [2021-yang-asd-nanodroplet-release-drug-properties-polymer-selection](../../../cards/2021-yang-asd-nanodroplet-release-drug-properties-polymer-selection/paper.html) · Dissolution / A. Release mechanism and LoC (ref C8)
- 2022 Hiew — [2022-hiew-lumefantrine-asd-stability-dissolution-polymer-choice](../../../cards/2022-hiew-lumefantrine-asd-stability-dissolution-polymer-choice/paper.html) · Solid state stability / Miscibility and drug-polymer interactions (ref 53)