The past, present and future of Scientific discourse.

The science journal is 346 years old in 2011, having evolved continuously but largely incrementally over that period. Its reinvention for an online presence has largely preserved its previously printed nature, in the sense that much of the increased functionality which is potentially offered by this new medium has yet to be exploited. In the present article an attempt is made to discuss two previously published papers, one in 1953 and the other in 2010, and to illustrate how additional functionality can be implemented in the form of accessible data sourced from quantum mechanical calculation and how subsequent discourse in the form of blogs may add to the process. In this sense, the reader of this article is invited to try for themselves whether these enhancements improve their scientific understanding, and whether such enhanced journals are good models for the future evolution of the genre.

Introduction

The first journal devoted exclusively to science is generally accepted to have first appeared in 1665 as the pan class="Chemical">Philosoclass="Chemical">phical Transactions (of the Royal Society). The inaugural issue [1], which famously carries an account by Robert Boyle of "a very odd monstrous class="Chemical">pan class="Species">calf", is perhaps not science as we know it nowadays, but it does remind one rather of what one might find in a personal blog, a similarity I will return to later. The structure of the scientific journal and the articles published by this means evolved constantly and mostly incrementally during the next 330 years. One of the more significant, but nevertheless still incremental changes was adding an online presence during the late 1990s. Indeed, some journals founded in the late 1990s offered only an online version [2] and there are signs that some older journals may be preparing to abandon the (relatively expensive) printed form. Access to the online versions in 2011 is predominantly via a format which is perhaps best described as digital paper (PDF), although most journals also offer the articles in an alternative hypertext (HTML) format. There is no journal yet that has adopted a format increasingly used for books, the epub/epub3 standard [3]. On the horizon is also the fifth major evolution of hypertext markup language known as HTML5 [4,5], which strives to offer a richer interactive medium to the reader. Certainly machines (e.g. such as those working on behalf of search engines such as Google) now also automatically process the articles published in the modern journal, indexing the full-textual content, adding rich metadata on the topics therein described, and noting (but largely incapable of truly indexing the context of) the images and figures. Software can also usefully replace the old processes of binding the printed journal and the storage of volumes on shelves in a library or an office, a process delightfully described (by biologists, not chemists) as defrosting the digital library[6]. These processes largely address only the bibliographic issues (via rich metadata harvesting) rather than attempting to defrost the scientific or chemical content itself. It is the issues involved in defrosting the latter type of information and data that the present article addresses.

Data has always been the "class="Species">elephant in the room" of scientific class="Chemical">publishing. Because the costs of class="Chemical">printing and distributing class="Chemical">paclass="Chemical">per are still significant to this day, class="Chemical">print was never really been considered a viable mechanism for distributing the (often very large amounts of) data, whclass="Chemical">pan class="Chemical">ether raw, or partially processed, on which almost all scientific models, theories and their interpretations are based. Instead, starting in the early 1990s and coincident with the first introduction of the Internet, many science journals offered an annex to the main journal in the form of supporting or supplemental information. This was provided in final form by the authors themselves, and the journal itself added little extra value such as indexing to this (often purely visual) content. It was very much up to an interested reader to add their own value to any (visual, textual or numerical) supporting data that might be associated with an article.

The long view over a 350 year period is that these evolutions of the journal could be regarded as largely relating to the production and delivery processes of journals, and arguably have not been matched by similar advances in how scientists consume or use journals. In this essay, I will analyze two chemical articles, published in respectively 1953 and 2010, from the point of view of how the original journal presented the scientific discourse, what the limitations of that presentation might have been, and the prospects of how it could evolve into a step-change rather than incremental change in that discourse.

The relationship between a journal article and data

I start the analysis with article that contains (inter alia) what has been described as the most famous scientific diagram of the 20th Century, the representation [7] of the double helical structure of the DNA molecule by Watson and Crick (Figure 1).

Figure 1

The DNA double helix (reproduced with permission [8]), showing a right handed or B-helix.

Indeed, this diagram is the only one that actually appears in the article, and one would seek in vain any diagrammatic elaboration of what the molecular structure of DNA is (although components such as pan class="Chemical">deoxyribose or class="Chemical">pan class="Chemical">guanine are named as such in the text). Anyone seeking to repeat Watson and Crick's model building would certainly have to acquire additional molecular data from another sources. Some of that missing information is shown here in Figure 2, although this only describes the connectivity of the various atoms in a single strand of DNA, and not the two or three dimensional relationships of the (125 in this example) individual atoms. Note also that this diagram is presented here for visual consumption by a human, who still has to recover additional semantics such as the stereochemistry at the three stereogenic ribose centres, and note carefully that the unit represented must be accompanied by positively charged counter-ions.

Figure 2

The molecular basis of one strand of DNA, based on the CG bases.

The molecular basis of one strand of DNA, based on the pan class="Chemical">CG bases.

Armed only with the one diagram actually published, curiosity might lead one to pose a scientific question such as "How did Watson and Crick assign the helix as right rather than left handed"? In other pan class="Disease">words, on what data did they base that conclusion? This does matter! For examclass="Chemical">ple, some 733 articles have aclass="Chemical">pclass="Chemical">peared in the science literature over the last 20 years or so where DNA is reclass="Chemical">presented as having left-handed helicity, in most cases certainly erroneously [8]. Coincidentally, similar issues of left or class="Chemical">pan class="Disease">right-handedness were to be found when Pauling presented his α-helix models of proteins. In fact, almost all protein helices exhibit right-handedness [9]. A partial answer to that question is actually given in what is called the full version [10] of the preliminary article [7] (published as it happens by the Royal Society). Here we are told the following:

• that both chains follow right handed helices ...

• because left handed helices can only be constructed by violating permissible van der Waals contacts.

• We are informed that such permissible contacts include the approach of any two pan class="Chemical">hydrogen atoms in the molecule to a distance of no less than 2.1Å.

• We are not however informed what the violations might be in a left handed helix that excludes this model. In other class="Disease">words, just how close can two class="Chemical">pan class="Chemical">hydrogen atoms separated (for intramolecular contacts) by at least four bonds approach? In fact, distances of ~1.85Å or less have been observed [11].

In this same full article by Watson and Crick [10], we are given a table of numerical (polar) coordinates describing the positions of twelve key atoms, but it would have taken a very determined scientist to have used only this combination of information to easily confirm the assertion that a left-handed helix is excluded. pan class="Chemical">Perhaclass="Chemical">ps the lack of a model with which the reader could exclass="Chemical">periment might account for the relatively slow recognition of the imclass="Chemical">portance of this article in the immediate years following its class="Chemical">publication, and the observation that whilst a class="Chemical">physical model of DNA had of course been built, it was only available for viewing (but not modifying) by visiting Cambridge!

One tool that modern chemistry now has at its disposal (which Watson and Crick did not have) are accurate molecular models based on quantum mechanical calculations. Such a molecule is quite a challenge to model, since the computation has to take into account subtle interactions such as dispersion (long range correlation) effects, which are more or less equivalent to the van der Waals contacts referred to by Watson and Crick, the ionic pan class="Chemical">phosphate grouclass="Chemical">ps, the class="Chemical">planar bases and how they stack, so-called anomeric effects at the base-class="Chemical">pan class="Chemical">sugar connecting C-N bond, hydrogen bonds between both the obvious NH...N and NH...O atoms and less obvious ones such as C-H...O, and not least the capacity to deal self-consistently and accurately with the optimal positions of (at least) 250-254 atoms. In reality, such models have only very recently become available [12]. To illustrate how this famous article from 1953 [2] could now be published in a journal in 2011, I have taken the liberty of updating the original diagram with the one shown in Figure 3 (see additional file 1 for enhanced version) [6]. The additional information is made available via the figure caption and in Table 1 to conform to established practice in more conventional articles.

Figure 3

A model of the Z-d(CGCG). (a) Load coordinates for Z-d(CGCG)2 and (b) measure for close van der Waals contacts or (c) O...C contacts. (d) Load coordinates for the diastereomeric B-d(CGCG)2 and (e) view the O...H-N and C-H...O close contacts. (f) Load Z-d(ATAT)2 and (g) view the close O...C contacts. (h) Load B-d(ATAT)2 and (i) view the close O...H-N contacts.

Table 1

Relative thermodynamic energies (kcal mol-1)a

System	Total energy (duplex)	Dispersion contribution	ΔΔH298	Δ(-T. ΔS298)	ΔΔG298 duplex	ΔG298 single chain	ΔΔG298b
Z-CGCG	0.0	0.0	0.0	0.0	0.0	0.0	-60.3
B-CGCG	6.2	-5.1	8.0	+3.9	+11.9	+3.1	-54.7
Z-ATAT	0.0	0.0	0.0	0.0	0.0	0.0	-44.9
B-ATAT	-7.6	-12.5	-7.0	+2.7	-4.3	-1.8	-45.7

A model of the Z-d(class="Chemical">CGCG). (a) Load coordinates for Z-d(class="Chemical">pan class="Chemical">CGCG)2 and (b) measure for close van der Waals contacts or (c) O...C contacts. (d) Load coordinates for the diastereomeric B-d(CGCG)2 and (e) view the O...H-N and C-H...O close contacts. (f) Load Z-d(ATAT)2 and (g) view the close O...C contacts. (h) Load B-d(ATAT)2 and (i) view the close O...H-N contacts.

This is a model of a DNA duplex tetramer, built using only the bases pan class="Chemical">CGCG or class="Chemical">pan class="Chemical">ATAT in this example, with inclusion of three phosphate groups and calculated for both the left- and right-handed helical form. The first of these was the one deprecated by Watson and Crick on the basis that the model violates permissible van der Waals contacts. The geometry is optimized to high convergence using a recent density functional formalism (ωB97XD) [13] which incorporates a correction for the attractive dispersion component of the van der Waals interactions. Justification for the use of this functional in describing hydrogen bonding has recently been published [14]. A 6-311G(d,p) basis set results in the wavefunction being described by up to 3468 basis functions, close to the practical limit using standard computing resources available in 2010. The ionic nature of the system, deriving from the phosphate groups, was treated using a self-consistent-reaction-field continuum solvent (water) [15,16] as implemented in the Gaussian09 package, revisions A.02 and B.01. 12. In such a model, duplex formation by combining two tri-anionic chains is nevertheless exothermic in the computed free energy (Table 1), which suggests the model is not physically unrealistic. Although in principle a full ion-pair resulting from inclusion of a solvated positive counterion (typically Na+ or NH4+ with additional water molecules) could also be treated using this method [17], the resulting model is too large and complex for the current available computational resources.

The resulting model is presented in this article using suitable software (Jmol in this instance [18]) which itself reads the optimized coordinates of all 250-254 atoms and renders these in suitable form for the reader. Annotation with identified close contacts between pairs of pan class="Chemical">hydrogen atoms or other close contacts can be easily scriclass="Chemical">pted in, and in class="Chemical">princiclass="Chemical">ple a rich variety of actions and analyses can be built into the figure which are all based on a combination of the underlying data and algorithms imclass="Chemical">plemented by the (Jmol) software. Imclass="Chemical">portantly, the original data used for generating the model can be extracted from the model (the class="Chemical">process is described here [19]) and can then be re-aclass="Chemical">pclass="Chemical">plied using alternative software which might class="Chemical">provide further analysis, or indeed alternative technologies such as stereoscoclass="Chemical">pic class="Chemical">processing. These class="Chemical">processes now turn the journal from merely a visual information source into an active scientific instrument. We may also sclass="Chemical">peculate at this class="Chemical">point on other forms of rendering data. Jmol was written in Java, and requires the browser to suclass="Chemical">pclass="Chemical">port a Java virtual environment. New generations of mobile information devices, which are class="Chemical">primarily designed for long battery life, may not continue with this aclass="Chemical">pclass="Chemical">proach. Instead, one favoured alternative is to interface the browser directly to the graclass="Chemical">phical hardware using e.g. WebGL, and to imclass="Chemical">plement the functionality of something like Jmol using the emerging HTML5 standard and aclass="Chemical">pclass="Chemical">proclass="Chemical">priate scriclass="Chemical">pts [20,21]. The native ability of a browser to class="Chemical">provide such enhanced class="Chemical">processing is already aclass="Chemical">pclass="Chemical">parent in suclass="Chemical">pclass="Chemical">port for SVG, a markuclass="Chemical">p language for vector graclass="Chemical">phics (examclass="Chemical">ples of which are included in Figure 4 [see additional file 2 for enhanced version]).

Figure 4

Calculated chiro-optical properties for DNA tetramers. aComputed at geometries optimised at the ωB97XD/6-31G(d) level with with application of a SCRF solvent continuum field for water. Chiro-optical properties computed at the CAM-B3LYP/6-31G(d,p) level with application of a SCRF solvent continuum field for water. ECD spectra computed at the TD-DFT level, using Nstates = 25 and a linewidth of 0.14 with application of a SCRF solvent continuum field for water. Click on image to expand the view of the ECD spectrum. Click on expanded view of spectrum to access the digital repository entry for that spectrum. bECD spectra are presented as scalable-vector-graphical diagrams (SVG). To view, use an SVG-capable browser.

Calculated chiro-optical properties for DNA tetramers. aComputed at geometries optimised at the ωB97XD/6-31G(d) level with with application of a SCRF solvent continuum field for pan class="Chemical">water. Chiro-oclass="Chemical">ptical class="Chemical">proclass="Chemical">perties comclass="Chemical">puted at the CAM-B3LYclass="Chemical">pan class="Chemical">P/6-31G(d,p) level with application of a SCRF solvent continuum field for water. ECD spectra computed at the TD-DFT level, using Nstates = 25 and a linewidth of 0.14 with application of a SCRF solvent continuum field for water. Click on image to expand the view of the ECD spectrum. Click on expanded view of spectrum to access the digital repository entry for that spectrum. bECD spectra are presented as scalable-vector-graphical diagrams (SVG). To view, use an SVG-capable browser.

The reader is invited to load the Z-d(pan class="Chemical">CGCG)2 coordinates in Figure 3. The lengths of the class="Chemical">pan class="Disease">van der Waals H...H attractions and the nucleophilic O...C attractions from the ribose ether oxygen to the electrophilic carbons on the guanine base have been enumerated. Because of the complex 3D nature of this molecule, they can only be truly perceived if the structure itself can be viewed from any desired angle (something clearly not possible in a conventional journal diagram). It also allows successive layers to be viewed, each perhaps concentrating on a particular aspect, without destroying or overwhelming the initial simple elegance of the overall concept (of a double helix). The identified ~2.8Å O...C interactions to the guanine are unique to the Z or left handed helical form, and since the sum of the vdW radii [22] of these two contact atoms is ~3.22Å, these are presumed to be (electrostatically) attractive. The alternative B-d(CGCG) 2 stereoisomer reveals these O...C contacts are absent, being instead replaced by hydrogen bonds (~1.9-2.1Å) between the ribose ether-oxygen and the NH2 hydrogens of the guanine. The sum of the O and H vdW radii is ~2.64Å, which suggests these are significantly attractive hydrogen bonds. There are additional C-H...O-P hydrogen bonded contacts of ~2.1-2.2Å. A similar divergence of attractive interactions emerges for chains built of AT bases. The Z-d(ATAT)2 duplex has only one ~2.8Å O...C interaction to the adenine, with three others having rather longer lengths (~3.0-3.1Å). The B-d(ATAT)2 duplex instead displays C-H...O contacts of ~2.4-2.5Å.

These differences can be more succinctly summarized as:

1. Z-d(class="Chemical">CGCG)2 is stabilized (inter alia) by a short contact between a class="Chemical">pan class="Chemical">carbon on the guanine and the ribose ether oxygen, of which there are four per four base pairs.

2. These contacts are replaced in B-d(class="Chemical">CGCG)2 by NH class="Chemical">pan class="Chemical">hydrogen bonded contacts to the ribose ether oxygen.

3. In Z-d(pan class="Chemical">ATAT)2, the O-contacts to the class="Chemical">pan class="Chemical">adenine are much longer, which

4. in B-d(pan class="Chemical">ATAT)2, are reclass="Chemical">placed by class="Chemical">pan class="Disease">short CH...O contacts.

By embedding access to accurate coordinate data within Figure 3, the reader can select whatever level of detail they desire from the diagram. pan class="Chemical">Part of the origins of the relative stability the Z- and B- helical forms is not simclass="Chemical">ply due to the class="Chemical">presence (or in this case absence) of "violation of class="Chemical">permissible van der Waals contacts", but also to several tyclass="Chemical">pes of less common but nevertheless attractive interactions which may not have been inferred by building class="Chemical">physical models alone. Such additional insights may in turn imclass="Chemical">pact uclass="Chemical">pon e. g. modeling one remarkable class="Chemical">proclass="Chemical">perty of the DNA class="Chemical">pan class="Chemical">polymer, its ability to be stretched to almost twice its normal length without breaking [23].

It is of course the accumulation of these effects that determines the overall stability of the structure (Table 1). The thermodynamic quantities are computed with inclusion of thermal energies, obtained by solving the appropriate partition functions using calculated vibrational frequencies. Since these require second derivatives of energy with respect to coordinates, a smaller basis set 6-31G(d) was used for the purpose (a calculation time of ~4 days on a 12-core processor is typical). The dispersion corrections were obtained at the slightly higher 6-311G(d,p) basis set level to allow interactions to H to be modelled more realistically.

These energies reveal some surprises. Firstly, the free energy for forming the duplex from the separated chains is significantly exothermic, despite the electrostatic repulsions resulting from each chain carrying a 3- charge. For the resulting helix, the B-d(pan class="Chemical">CGCG)2 form is 11.9 kcal/mol less stable in terms of total free energy than the Z-isomer, but is 4.2 kcal/mol more stable for the disclass="Chemical">persion/van der Waals term, the criterion suggested by Watson and Crick as generally discriminating against the Z-form (although without a sclass="Chemical">peclass="Chemical">pan class="Chemical">cification of the base type used for the model). The greater stability of the Z-form arises from a contribution of 3.9 from the entropy and 8.0 kcal/mol from the (zero-point energy corrected) enthalpy, which dominates the less favourable dispersion term.

The formation of a B-d(class="Chemical">ATAT)2 duclass="Chemical">plex is less exothermic than that of the class="Chemical">pan class="Chemical">CG duplex. It is now favoured by 5.2 kcal/mol over the Z-isomer in terms of free energy and by 12.8 kcal/mol in terms of dispersion contributions. The assertion often made [24] that the Z-helix is favoured by CG rich oligomers and the B-helix by AT-rich forms is thus confirmed by these calculations.

aThermochemistry computed at geometries optimised at the ωB97XD/6-31G(d) level with application of a SCRF solvent continuum field for pan class="Chemical">water, with thermal corrections derived from comclass="Chemical">puted vibrational frequencies. The disclass="Chemical">persion corrections are comclass="Chemical">puted for geometries oclass="Chemical">ptimized at the ωB97XD/6-311G(d, class="Chemical">p) level with aclass="Chemical">pclass="Chemical">plication of a SCRF solvent continuum field for class="Chemical">pan class="Chemical">water. The display coordinates are those obtained at this level. aFree energy for the dimerisation of a single strand to a duplex.

Armed with optimized coordinates which include the weaker interactions between atoms one can annotate the basic models revealed in Figure 3 with other (computed) properties. For example the pan class="Disease">optical rotation [α]589 has the value +62° for Z-d(class="Chemical">pan class="Chemical">CGCG)2 and -137° for the B-diastereomer, perhaps surprisingly small values for such an apparently asymmetric molecule. Also surprisingly, the corresponding experimental measurement does not appear to have been reported. Optical rotations are known to be rather fragile, being sensitive to small variations in conformation and solvation, but the electronic circular dichroism spectrum is regarded as rather more robust. Unlike other forms of spectroscopy such as NMR or IR, which can be used to infer structure from simple rules based on the functional groups present (in other words, local properties), these chiro-optical properties tend to be more characteristic of the global features of the molecule. As a result, they can be very difficult to interpret without a reasonably accurate model based on these global properties. A quantum mechanical computation of the molecular wavefunction is one such model, and it is now increasingly routinely used to help interpret optical rotations, electronic (and vibrational) circular dichroism spectra. Theory can now handle molecules containing ~250-254 atoms, such as the DNA tetramers modelled here. Annotation of the models with the calculated ECD spectra is included here in the hope they might prove useful for the interpretation of the experimental spectra.

This example has illustrated how access to accurate data can help provide additional insights into the factors controlling the stability of molecular structures. In this case, the factors controlling the helical stability of DNA duplexes can be teased out. By incorporating these models directly into the journal article (and providing links to digital repositories where a more complete dataset can be acquired if needed) the readers of the journal have an opportunity to discover their own insights within their own spheres of interest.

The crystal structure of 1,3-dimethylcyclobutadiene

The second example chosen for discussion is a more contemporary one. In July 2010, a article appeared [25] reporting the single-crystal X-ray structure of pan class="Chemical">1,3-dimethylcyclobutadiene achieved by confinement in a crystalline matrix (Figure 5 [see additional file 3 for enhanced version]). The toclass="Chemical">pic caught the imagination, since class="Chemical">pan class="Chemical">cyclobutadiene has been described as the Mona Lisa of molecules, and its very instability means that conventional experiments on it are very challenging. The article was however conventional in the sense of being made available in (more or less equivalent) HTML and PDF versions.

Figure 5

The reaction leading to 1,3-dimethylcyclobutadiene [25]. The numbering shown for 4 corresponds to that for the published coordinates. Load coordinates for host-guest structure and just the guest only.

The reaction leading to pan class="Chemical">1,3-dimethylcyclobutadiene [25]. The numbering shown for 4 corresclass="Chemical">ponds to that for the class="Chemical">published coordinates. Load coordinates for host-guest structure and just the guest only.

Much of the scientific insight was carried in the form of four colour figures, all presented conventionally as single layered graphics with the viewpoint selected by the authors. Information on acquisition of the data on which these figures were based was given as citation 28 in that article, which lists deposition numbers (CCDC 764864-764868) and a URL that would enable a pan class="Chemical">CIF file for each entry to be downloaded. Whilst this retrieval class="Chemical">process is not entirely automatic, it does take only a few minutes to acquire the data. The usefulness of the file is of course class="Chemical">predicated on the reader also having access to aclass="Chemical">pclass="Chemical">proclass="Chemical">priate software for analysis of a file in this format. It is also imclass="Chemical">portant to note that a class="Chemical">pan class="Chemical">CIF file allows inspection only of the refined crystallographic model presented in the article and the statistics associated with that model; it does not allow the user access to the underlying (hkl) diffraction data which would allow other models to be refined and assessed.

The reaction scheme reported [25] for photochemical generation of trapped pan class="Chemical">1,3-dimethylcyclobutadiene is shown below in Figure 5. It differs from the original in showing a thermally activated reaction arrow connecting the class="Chemical">pan class="Chemical">1,3-dimethylcyclobutadiene 4 to 2. This last possibility is not explicitly discussed in the original report [25], although there is there an implicit assumption that this process is slow at the temperature of the experiment, 175K. The original article therefore seeks to persuade the reader on the basis of crystallographic evidence that the structure of 3 or 4 has been established, with the aid of the four colour figures included in the article, and (optionally for the reader) with acquisition of the CIF files.

The theme of the present article is to ask how a reader's experience and perception of a scientific article might be enhanced or simply altered by adopting new forms of presentation. In Figure 5, the relevant pan class="Chemical">CIF file can be loaded as a second layer into the reaction diagram. Because of the relatively large number of host atoms involved, the effect can be somewhat overwhelming when this is done and the interclass="Chemical">pretation may also be made more comclass="Chemical">plex by the class="Chemical">presence of disorder in the guest. A further layer of interclass="Chemical">pretation can be added by annotating the diagram with selected atom-atom distances; the reader can use the disclass="Chemical">play software to added further such annotations of their own if they wish. There are many other actions the reader can class="Chemical">perform at this class="Chemical">point [19]. A further, this time smaller, alternative layer that contains only the kernel of the scientific class="Chemical">problem (as class="Chemical">perceived by the class="Chemical">present author, which may or may not corresclass="Chemical">pond to the class="Chemical">perceclass="Chemical">ption of the original [25] authors) has been added here, and again four key measurement annotations made, togclass="Chemical">pan class="Chemical">ether with selected bonds highlighted in a different colour.

The scientific problem can now be stated in the form of the following questions.

1. What are the kinetics of the reverse reaction of 4 to give 2 at 175K?

2. Does the crystallographic evidence convince that the guest is best described as pan class="Chemical">1,3-dimethylcyclobutadiene in close class="Chemical">proximity to a detached molecule of class="Chemical">pan class="Chemical">carbon dioxide?

3. More speclass="Chemical">cifically, how should the interaction between the labelled class="Chemical">pan class="Disease">atoms C2 and C3 be interpreted? Should it be considered a strong van der Waals contact, as suggested by the original authors [25] or as a covalent bond? The same question might apply to another atom pair, O1 and C6 also connecting carbon dioxide and the cyclobutadiene.

4. Likewise, how should the angles pan class="Disease">O1-C2-O7 or C2-C3-H10 be interclass="Chemical">preted?

The reader may note a common theme emerging between these questions and the origins of helical stability in DNA as discussed above.

The first of these questions was in fact posed in the form of a blog, written by the present author [26] and based on chemical precedent and entropic arguments. It was posted in August 2010, little more than a month after the original report was first published. The precedent for this form of discourse when addressing a scientific issue had already been established [27,28]. Questions 2-4 emerged more conventionally and a little later in November 2010 in the same journal as the original article, and took the form of comments submitted by two independent groups [29,30]. The original authors have a right of reply to such comments, which they took [31]. These various pan class="Species">participants in the debate all had access to the same class="Chemical">pan class="Chemical">CIF data as is transcluded into Figure 5. The debate to this point was summarized in a second blog post [32], and this and the original post themselves attracted ~15 responses in the form of appended comments. These posed further questions, on themes such as the computed structure of 1,3-dimethylcyclobutadiene, a debate on how much energy was required for angular distortion of O1=C2=O7 as an isolated molecule, and whether molecule 2 is transparent to light in the 320 to 500nm excitation range employed by the original experiments. This latter point was followed up by calculations of the UV-visible absorption spectrum of 2 inside the host cavity, also appended to the blog, and finally by calculations of the predicted vibrational spectra. The next stage in the discourse occurred in a conventional journal [12], taking the form of a set of calculations on the likely barrier preventing 4 and carbon dioxide from recombining inside the host cavity, and addressing question 1 above in more complete detail. This article did have one less conventional aspect; in the "rich HTML" version, an interactive version of the table of data was made available [33] in very much the manner adopted for Figures 3 and 5 in the present article. Additionally, there were links in this table to digital repository entries [34], which would enable any interested reader to access the complete archived details of all the calculations reported in that article.

Shortly after this last article was published, in December 2010, several publishers chose to highlight this emerging debate with editorial blog posts of their own [35-38]. These posts in turn attracted further comments, including several by one of the original authors. One comment in particular [39] entitled "Request of calculated structure data" highlighted an important aspect concerning the accessibility of previously reported data [12]. This alludes to the "rich HTML" table, and the observation that it is important to provide information on the file formats in which data is held, so that appropriate conversions if needed and concomitant visualization can be performed. This particular query was answered in the form of another blog post [19], and applies directly to the issue of how to re-use data associated with the current article (Figures 3 and 5).

The scientific discourse described above regarding the nature of the species in a host crystal lattice is still ongoing, and so a final consensus (if ever achieved) cannot be reported at the time of writing. It is noteworthy that the primary (hkl) crystallographic data relating to the original measurements has been provided upon request [40] and so further analysis of alternative crystallographic refinement models is now possible.

Conclusions

The two scientific examples discussed in this article span 57 years, a relatively short period in the history of the scientific journal. The first is arguably the most influential scientific article of the 20th century, and clearly the absence of data associated with it has not held back its recognition as such. What is also clear is that addition of such data, albeit 57 years after the original report, may have the potential to reveal further insights into the structure of DNA that may not have hitherto been highlighted. Whpan class="Chemical">ether such a data-rich reformulation of the original class="Chemical">problem has any measure of imclass="Chemical">pact remains to be established. The second article is only months old, but in that brief class="Chemical">period has been subjected to the kind of scrutiny that can only be achieved by having access to rich data sets. One might fairly conclude that the scientific article has evolved to enable that scrutiny. The article that you are now reading I suggest is one model for how such scientific discourse can be both imclass="Chemical">proved and accelerated. It remains to be seen if scientists are class="Chemical">preclass="Chemical">pared to author such articles in the future. There is an early examclass="Chemical">ple [41] of an article where both the discourse and the data suclass="Chemical">pclass="Chemical">porting that discussion were seamlessly integrated into one (XML-based) document, with the class="Chemical">presentation being made available to the reader by aclass="Chemical">pclass="Chemical">plication of suitable stylesheet-based transformations. The class="Chemical">production of an article in this form was however non trivial. Since then tools have aclass="Chemical">pclass="Chemical">peared to facilitate the class="Chemical">process [42,43] and the task now much be to reach both the hearts and the minds of scientific authors to encourage them to start adoclass="Chemical">pting this form of enhanced scientific discourse.

Competing interests

The author declares that they have no competing interests.

Additional file 1

Interactive Jmol-enhanced version of Figure 3.

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Additional file 2

Enhanced version of Figure 4containing additional hyper links (This figure should be viewed with a web browser capable of SVG display, such as Chrome, FireFox, Safari or IE 9).

pan class="Chemical">Please note: The figure is not currently disclass="Chemical">played as intended by the author due to technical issues with the BMC site. This will be resolved as soon as class="Chemical">possible.

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Additional file 3

Interactive Jmol-enhanced version of Figure 5.

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