Readers call for cross-industry support, celebrate variety and debate the evidence for Z-DNA’s handedness 

Something in the water

I read with interest that trihalomethane levels in Irish drinking water were ruled as too high by the European court. While these compounds are formed as a result of disinfection, long-term exposure could pose risks to health and the environment.

In Australia, heavy investment has been made to grow commercial amounts of red seaweed containing high levels of trihalomethanes. The seaweed is used in dairy and cattle feed to reduce methane emissions from the enteric microbiome. The use of these feed supplements is not regulated. While water authorities are aware of the risks of long-term exposure, it is unclear whether similar awareness has developed along with this new agricultural input material – whether in production or inclusion in the food chain.

Perhaps the water industry can assist agriculture in controlling unnecessary exposures?

JH Fitton FRSC
Sydney, Australia

Variety shown

Even though I am in the middle of my ninth decade, my mind still buzzes with chemistry and I cherish my long association with the Royal Society of Chemistry. I attended the inaugural meeting of the Heterocyclic Chemistry Group in 1965 and published my first paper in J. Chem. Soc. in 1964 and the last (but not the final one!) in RSC Chemical Biology in 2023, a gap of 60 years. Notable, but probably not unique.

I look forward to receiving my copy of Chemistry World every month as a means of keeping in touch with the wider field. Although my main expertise lay in the synthesis of small biologically-active molecules (rather dated, maybe?), I find that I can appreciate the well-selected diversity of articles. For example in the March issue of the magazine, I read every page with interest.

Please keep up the variety and quality, for myself and fellow veterans.

Malcolm Stevens FRSC
Arnside, UK

A–Z of DNA

The study of nucleic acid structure has excited more than its fair share of controversy and disputes. However, Clive Delmonte states in his letter that there is doubt about the handedness of this well-studied polymorph of the DNA double helix. In reality there is none.

He incorrectly asserts that the assignment of left-handedness to Z-DNA is based on model-fitting and conjecture, and is open to dispute. The seminal publication by Alexander Rich’s group describing the crystal structure determination of a left-handed Z-DNA (AH-J Wang et al, Nature, 1979, 282, 680) used the method of multiple isomorphous replacement (MIR) for structure determination. MIR was pioneered by Max Perutz and John Kendrew for the first determinations of protein crystal structures. It does not rely on any assumptions of molecular models for structure determination, and structures emerge from electron-density maps without any preconceptions or bias as to the nature of the structure.

Rich et al were able to unequivocally demonstrate that Z-DNA is left-handed, supporting the earlier 1972 suggestion of Fritz Pohl and Thomas Jovin, based on circular dichroism measurements of an alternating C-G polynucleotide.

This conclusion of left-handedness has been confirmed and extended by many subsequent crystal structure analyses, including several studies of left-handed Z-DNAs bound to functional proteins. A notable example (SC Ha et al, Nature, 2005, 437, 1183) shows a DNA sequence in a conventional right-handed B-from double helix for part of its length and the remainder in the left-handed Z-form, bound to a protein.

Stephen Neidle FRSC
University College London, UK

I started reading the letter from Clive Delmonte with interest until I came to the second paragraph, when I was left wondering what Delmonte considers to be ‘direct physical experimentation’.

Since the 1910s, collecting crystallographic x-ray data has been considered to be direct physical experimentation (I am left wondering what is indirect about illuminating a crystal with a collimated beam of x-rays and recording the diffraction pattern). The data derived from these experiments has been used to build structural models of chemical species. Perhaps someone should tell the CCDC and the PDB that their databases are built on a foundation of sand, or major governments of the world that the billions of pounds spent on synchrotrons and XFELs is merely pandering to the vanity of crystallographers?

Alexander Rich’s group solved the Z-DNA structure by the method of multiple isomorphous replacement (also known as the ‘heavy atom method’), so no prior nucleotide model was used to fit a structure to the calculated electron density. The reported residual index of 14% at 0.9Å resolution in the original Nature paper would be considered to be more than adequate by today’s standards and indicates that the model is unambiguously correct.

In any case, ‘fitting models they had built to their crystallographic diffraction pattern’ is exactly what thousands of crystallographers, both in the small and macromolecular fields, do every day; x-ray crystal structure determination has become the gold standard of solid state structure analysis. Moreover, what do NMR spectroscopists or electron microscopists (or indeed, all scientists) do other than fit models to their data? Denying this is denying the progress of science itself, which is the progressive development of models that fit the data better than previous models.

Harry Powell CChem MRSC
Via email