Molecular Insights into the Crystallization of 4’-Hydroxyacetophenone from Water: Solute Aggregation, Liquid–Liquid Phase Separation, and Polymorph Selection

In this work, insights into the structural rearrangements occurring in aqueous solution, prior to the nucleation of different 4’-hydroxyacetophenone (HAP) forms from water, were obtained, through a combination of thermomicroscopy, microdifferential scanning calorimetry, density and speed of sound me...

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Main Author: Carlos E. S. Bernardes (7183481) (author)
Other Authors: Ricardo G. Simões (1648846) (author), M. Soledade C. S. Santos (11324211) (author), Pedro L. T. Melo (9736546) (author), Ângela F.S. Santos (20944040) (author), Stéphane Veesler (1784740) (author), Manuel E. Minas da Piedade (7183487) (author)
Published: 2025
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author Carlos E. S. Bernardes (7183481)
author2 Ricardo G. Simões (1648846)
M. Soledade C. S. Santos (11324211)
Pedro L. T. Melo (9736546)
Ângela F.S. Santos (20944040)
Stéphane Veesler (1784740)
Manuel E. Minas da Piedade (7183487)
author2_role author
author
author
author
author
author
author_facet Carlos E. S. Bernardes (7183481)
Ricardo G. Simões (1648846)
M. Soledade C. S. Santos (11324211)
Pedro L. T. Melo (9736546)
Ângela F.S. Santos (20944040)
Stéphane Veesler (1784740)
Manuel E. Minas da Piedade (7183487)
author_role author
dc.creator.none.fl_str_mv Carlos E. S. Bernardes (7183481)
Ricardo G. Simões (1648846)
M. Soledade C. S. Santos (11324211)
Pedro L. T. Melo (9736546)
Ângela F.S. Santos (20944040)
Stéphane Veesler (1784740)
Manuel E. Minas da Piedade (7183487)
dc.date.none.fl_str_mv 2025-03-27T09:33:44Z
dc.identifier.none.fl_str_mv 10.1021/acs.cgd.5c00117.s003
dc.relation.none.fl_str_mv https://figshare.com/articles/media/Molecular_Insights_into_the_Crystallization_of_4_-Hydroxyacetophenone_from_Water_Solute_Aggregation_Liquid_Liquid_Phase_Separation_and_Polymorph_Selection/28675553
dc.rights.none.fl_str_mv CC BY-NC 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biophysics
Biochemistry
Medicine
Evolutionary Biology
Ecology
Sociology
Marine Biology
Cancer
Computational Biology
Environmental Sciences not elsewhere classified
Chemical Sciences not elsewhere classified
Physical Sciences not elsewhere classified
structural rearrangements occurring
remain approximately invariant
microdifferential scanning calorimetry
4 ’- hydroxyacetophenone
molecular dynamics simulations
already initially present
different crystal forms
2 </ sub
solution initially evolve
solution concentration increases
hap </ sub
zone iii ),
initially present
x </
zone iii
>< sub
solution properties
aqueous solution
whole system
transition region
temperature decreases
start converging
sound measurements
solvated clusters
solute aggregation
selectively leads
results confirmed
range corresponds
process increases
process accompanied
previous observation
polymorph selection
physical properties
molecular insights
large hap
even percolate
certain point
anhydrous form
also reduce
abruptly change
dc.title.none.fl_str_mv Molecular Insights into the Crystallization of 4’-Hydroxyacetophenone from Water: Solute Aggregation, Liquid–Liquid Phase Separation, and Polymorph Selection
dc.type.none.fl_str_mv Dataset
Media
info:eu-repo/semantics/publishedVersion
dataset
description In this work, insights into the structural rearrangements occurring in aqueous solution, prior to the nucleation of different 4’-hydroxyacetophenone (HAP) forms from water, were obtained, through a combination of thermomicroscopy, microdifferential scanning calorimetry, density and speed of sound measurements, and molecular dynamics simulations. The results confirmed our previous observation that cooling crystallization of HAP is intermediated by liquid–liquid phase separation (LLPS) and, depending on the initially selected concentration range, selectively leads to the formation of different crystal forms. Analysis of the solution properties before the onset of LLPS revealed that, in the HAP mole fraction range <i>x</i><sub>HAP</sub> < 0.004 (Zone I), where hydrate H2 ultimately crystallizes, small, solvated clusters are initially present in solution, which remain approximately invariant in size, shape, and HAP/H<sub>2</sub>O proportion as the temperature decreases. For the <i>x</i><sub>HAP</sub> > 0.005 range (Zone III), where anhydrous form I crystallizes, large HAP/water aggregates (that can even percolate the whole system as <i>x</i><sub>HAP</sub> approaches the 0.005 limit) are already initially present in solution. As cooling progresses, they become more compact, a process accompanied by a reduction in water content, which is more significant as the solution concentration increases. The 0.004 < <i>x</i><sub>HAP</sub> < 0.005 (Zone II) range corresponds to a transition region where, as <i>x</i><sub>HAP</sub> increases, the physical properties of the solution initially evolve from those typical of Zone I and, at a certain point, abruptly change and start converging to those typical of Zone III. In all zones, the colloidal particles formed upon LLPS (from which crystallization results) can also reduce their water content on cooling, but the extent of this process increases as <i>x</i><sub>HAP</sub> moves from Zones I and II, where hydrates are formed, to Zone III, where anhydrous form I is produced.
eu_rights_str_mv openAccess
id Manara_d657c8d8ebfa342cdb45ff9697036c62
identifier_str_mv 10.1021/acs.cgd.5c00117.s003
network_acronym_str Manara
network_name_str ManaraRepo
oai_identifier_str oai:figshare.com:article/28675553
publishDate 2025
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
rights_invalid_str_mv CC BY-NC 4.0
spelling Molecular Insights into the Crystallization of 4’-Hydroxyacetophenone from Water: Solute Aggregation, Liquid–Liquid Phase Separation, and Polymorph SelectionCarlos E. S. Bernardes (7183481)Ricardo G. Simões (1648846)M. Soledade C. S. Santos (11324211)Pedro L. T. Melo (9736546)Ângela F.S. Santos (20944040)Stéphane Veesler (1784740)Manuel E. Minas da Piedade (7183487)BiophysicsBiochemistryMedicineEvolutionary BiologyEcologySociologyMarine BiologyCancerComputational BiologyEnvironmental Sciences not elsewhere classifiedChemical Sciences not elsewhere classifiedPhysical Sciences not elsewhere classifiedstructural rearrangements occurringremain approximately invariantmicrodifferential scanning calorimetry4 ’- hydroxyacetophenonemolecular dynamics simulationsalready initially presentdifferent crystal forms2 </ subsolution initially evolvesolution concentration increaseshap </ subzone iii ),initially presentx </zone iii>< subsolution propertiesaqueous solutionwhole systemtransition regiontemperature decreasesstart convergingsound measurementssolvated clusterssolute aggregationselectively leadsresults confirmedrange correspondsprocess increasesprocess accompaniedprevious observationpolymorph selectionphysical propertiesmolecular insightslarge hapeven percolatecertain pointanhydrous formalso reduceabruptly changeIn this work, insights into the structural rearrangements occurring in aqueous solution, prior to the nucleation of different 4’-hydroxyacetophenone (HAP) forms from water, were obtained, through a combination of thermomicroscopy, microdifferential scanning calorimetry, density and speed of sound measurements, and molecular dynamics simulations. The results confirmed our previous observation that cooling crystallization of HAP is intermediated by liquid–liquid phase separation (LLPS) and, depending on the initially selected concentration range, selectively leads to the formation of different crystal forms. Analysis of the solution properties before the onset of LLPS revealed that, in the HAP mole fraction range <i>x</i><sub>HAP</sub> < 0.004 (Zone I), where hydrate H2 ultimately crystallizes, small, solvated clusters are initially present in solution, which remain approximately invariant in size, shape, and HAP/H<sub>2</sub>O proportion as the temperature decreases. For the <i>x</i><sub>HAP</sub> > 0.005 range (Zone III), where anhydrous form I crystallizes, large HAP/water aggregates (that can even percolate the whole system as <i>x</i><sub>HAP</sub> approaches the 0.005 limit) are already initially present in solution. As cooling progresses, they become more compact, a process accompanied by a reduction in water content, which is more significant as the solution concentration increases. The 0.004 < <i>x</i><sub>HAP</sub> < 0.005 (Zone II) range corresponds to a transition region where, as <i>x</i><sub>HAP</sub> increases, the physical properties of the solution initially evolve from those typical of Zone I and, at a certain point, abruptly change and start converging to those typical of Zone III. In all zones, the colloidal particles formed upon LLPS (from which crystallization results) can also reduce their water content on cooling, but the extent of this process increases as <i>x</i><sub>HAP</sub> moves from Zones I and II, where hydrates are formed, to Zone III, where anhydrous form I is produced.2025-03-27T09:33:44ZDatasetMediainfo:eu-repo/semantics/publishedVersiondataset10.1021/acs.cgd.5c00117.s003https://figshare.com/articles/media/Molecular_Insights_into_the_Crystallization_of_4_-Hydroxyacetophenone_from_Water_Solute_Aggregation_Liquid_Liquid_Phase_Separation_and_Polymorph_Selection/28675553CC BY-NC 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/286755532025-03-27T09:33:44Z
spellingShingle Molecular Insights into the Crystallization of 4’-Hydroxyacetophenone from Water: Solute Aggregation, Liquid–Liquid Phase Separation, and Polymorph Selection
Carlos E. S. Bernardes (7183481)
Biophysics
Biochemistry
Medicine
Evolutionary Biology
Ecology
Sociology
Marine Biology
Cancer
Computational Biology
Environmental Sciences not elsewhere classified
Chemical Sciences not elsewhere classified
Physical Sciences not elsewhere classified
structural rearrangements occurring
remain approximately invariant
microdifferential scanning calorimetry
4 ’- hydroxyacetophenone
molecular dynamics simulations
already initially present
different crystal forms
2 </ sub
solution initially evolve
solution concentration increases
hap </ sub
zone iii ),
initially present
x </
zone iii
>< sub
solution properties
aqueous solution
whole system
transition region
temperature decreases
start converging
sound measurements
solvated clusters
solute aggregation
selectively leads
results confirmed
range corresponds
process increases
process accompanied
previous observation
polymorph selection
physical properties
molecular insights
large hap
even percolate
certain point
anhydrous form
also reduce
abruptly change
status_str publishedVersion
title Molecular Insights into the Crystallization of 4’-Hydroxyacetophenone from Water: Solute Aggregation, Liquid–Liquid Phase Separation, and Polymorph Selection
title_full Molecular Insights into the Crystallization of 4’-Hydroxyacetophenone from Water: Solute Aggregation, Liquid–Liquid Phase Separation, and Polymorph Selection
title_fullStr Molecular Insights into the Crystallization of 4’-Hydroxyacetophenone from Water: Solute Aggregation, Liquid–Liquid Phase Separation, and Polymorph Selection
title_full_unstemmed Molecular Insights into the Crystallization of 4’-Hydroxyacetophenone from Water: Solute Aggregation, Liquid–Liquid Phase Separation, and Polymorph Selection
title_short Molecular Insights into the Crystallization of 4’-Hydroxyacetophenone from Water: Solute Aggregation, Liquid–Liquid Phase Separation, and Polymorph Selection
title_sort Molecular Insights into the Crystallization of 4’-Hydroxyacetophenone from Water: Solute Aggregation, Liquid–Liquid Phase Separation, and Polymorph Selection
topic Biophysics
Biochemistry
Medicine
Evolutionary Biology
Ecology
Sociology
Marine Biology
Cancer
Computational Biology
Environmental Sciences not elsewhere classified
Chemical Sciences not elsewhere classified
Physical Sciences not elsewhere classified
structural rearrangements occurring
remain approximately invariant
microdifferential scanning calorimetry
4 ’- hydroxyacetophenone
molecular dynamics simulations
already initially present
different crystal forms
2 </ sub
solution initially evolve
solution concentration increases
hap </ sub
zone iii ),
initially present
x </
zone iii
>< sub
solution properties
aqueous solution
whole system
transition region
temperature decreases
start converging
sound measurements
solvated clusters
solute aggregation
selectively leads
results confirmed
range corresponds
process increases
process accompanied
previous observation
polymorph selection
physical properties
molecular insights
large hap
even percolate
certain point
anhydrous form
also reduce
abruptly change