Knowing exactly how a molecule sits in the crystal lattice — and which enantiomer you are working with — underpins patent protection, regulatory submissions and process understanding.
PCL Research & Manufacturing determines the three-dimensional structure of your solid forms and assigns the absolute configuration of chiral APIs, combining X-ray, neutron and electron diffraction techniques.
Each technique answers a different question. Together they cover the full range of samples encountered in drug development — from well-formed single crystals to sub-micron powders that cannot be grown any larger.
A determined structure is the highest level of evidence available about a solid form. It settles polymorph identity beyond argument, establishes hydrogen bonding and packing, locates water and solvent in the lattice, and assigns stereochemistry unambiguously. For patent prosecution and for regulatory questions about chirality, that unambiguity is the entire point.
The choice of technique is dictated by what your material will give us, not by what is most convenient to run.
The reference method when a suitable single crystal can be grown. Laboratory diffraction resolves most structures; synchrotron radiation extends the reach to very small, weakly diffracting or twinned crystals.
For crystals too small or too poorly diffracting for a laboratory source. The intensity available at a synchrotron makes structures accessible that would otherwise be out of reach.
Neutrons are scattered by hydrogen almost as strongly as by heavier atoms, so hydrogen positions can be located directly — decisive for hydrogen bonding, hydrate structures and the salt versus co-crystal distinction.
MicroED determines structures from crystals of sub-micron size — the powders that cannot be grown larger, and that until recently were simply undeterminable.
Assignment of the absolute configuration of chiral APIs, establishing which enantiomer is present rather than inferring it from synthesis or optical rotation.
Packing, hydrogen bonding networks, conformation, solvent and water positions, and what they imply for stability, solubility and mechanical behaviour.
Most of the effort usually goes into obtaining a suitable crystal; where that proves impossible, electron diffraction changes the question.
The material is examined by microscopy and diffraction to establish crystal quality, size and whether a single-crystal route is realistic.
Where no suitable crystal exists, we run crystal growth experiments specifically aimed at producing diffraction-quality material — a different objective from ordinary crystallization.
Based on the crystals obtained, the determination proceeds by laboratory single crystal XRD, synchrotron, neutron or electron diffraction.
Diffraction data are collected at the appropriate temperature, with the strategy chosen for the resolution and completeness the structure requires.
The structure is solved and refined to convergence, with disorder, twinning and solvent treated explicitly rather than masked.
For chiral compounds, the absolute structure is determined and its reliability assessed and reported honestly.
The structure is interpreted in the context of your development question and delivered with the crystallographic data.
Determinations are carried out in our laboratory and, where the sample requires it, at large-scale facilities through established collaborations.
The deliverable is a detailed technical-scientific report together with the crystallographic files a reviewer or patent attorney will ask for.
No — and this is the reason MicroED matters. Electron diffraction determines structures from crystals of sub-micron size, which means the powder you already have is frequently sufficient. Structure solution from powder diffraction data is a further option.
When hydrogen positions are the question. X-rays scatter weakly from hydrogen, so hydrogen atoms are inferred rather than seen. Neutrons locate them directly, which is decisive for hydrogen bonding, hydrate structures and for distinguishing a salt from a co-crystal by proton position.
Modern diffraction methods and data quality make absolute structure determination feasible for many light-atom compounds, though the reliability depends on the specific molecule and the data. We assess it case by case and report the confidence in the assignment rather than stating it flatly.
Yes, and it is one of the most common reasons clients commission the work. A crystal structure is the strongest available characterization of a solid form, and the crystallographic data are delivered in the form attorneys and examiners expect.
Yes. Our facility is authorized to handle high-potency active pharmaceutical ingredients up to OEB5, and controlled substances under Ministry of Health authorization, under GMP certification issued by AIFA and following FDA inspection.
It depends almost entirely on the sample. Where a suitable crystal already exists, the determination itself is quick; where crystals have to be grown, or where synchrotron or neutron beamtime is required, the timeline is governed by those steps. We tell you what the sample implies once we have seen it.
Very little for single crystal work — one good crystal. For crystal growth experiments and for electron diffraction the requirement is modest, and we confirm it when we assess the sample.
Work starts only after a confidentiality agreement is in place. Structures, data and reports remain yours, and results are never published or shared without your written agreement.
Send us the sample, or tell us what you have been unable to crystallize. We will assess it and tell you which technique gives you an answer.