Increase at c.390 nm
Increase at c. 330 nm
Increase at c.373 nm
Abbreviations: β-CD, β-cyclodextrin; BDF, bis-dimethylaminofuchsone; BM, Brooker’s merocyanine; ET33, 2, 6-dichloro-4-(2, 4, 6-triphenyl-pyridinium-1-yl)-phenolate; MV, methylene violet (Bernthsen); 4PP, 4-pyridinium phenolate.
a Positively solvatochromic dyes.
b Negatively solvatochromic dyes.
c β-cyclodextrin concentration 10 mM/buffer concentration 20 mM (pH 8.5 and 9.0 borate; pH 11.0 CAPS).
The current study has considerably extended the range of compounds that respond to homeopathic potencies. Solvatochromic dyes now seem to be a sub-group of a larger class of compounds known as π-conjugated dipoles demonstrating interactions with serially diluted and succussed solutions. These include amino acids with an aromatic bridge (π-conjugated zwitterions). The presence of a large dipole moment, electron delocalisation, polarizability (the ability for electron density to shift across the molecule under an appropriate stimulus) and molecular rigidity seem to be general requirements in compounds for significant interactions with potencies to take place. Two particular compounds of this wider class which are readily available and provide significant spectroscopic responses to potencies are ANA and DANDSA, the latter demonstrating changes in its spectra of 8 to 10% over time. shows a plot of percentage change in dye spectra versus dye dipole moment. Some uncertainty exists over the ground or permanent dipole moment size for several compounds used in this study as their values are not available in the literature, but reasonable estimates can be made according to established principles. Despite these minor uncertainties in dipole moment size, the general trend is clear. The larger the size of the dipole moment of a compound, the larger the response to potencies appears to be. PB, examined previously, has the smallest ground dipole moment and produces the smallest response. Conversely MV, BM, and DANDSA have the largest dipole moments and produce the largest responses. In addition, comparing ABA with ANA, where the only difference is the distance between charged moieties, and hence dipole moment, a threefold increase in response is seen.
Fig. 12 Plot of percentage change in dye spectra versus dye ground or permanent dipole moment for solvatochromic compounds (upper plot) and non-solvatochromic compounds (lower plot) used in this study. 4ABA, 4-Aminobenzoic acid; ABPA, 4′-amino-[1,1′-biphenyl]-4-carboxylic acid; ANA, 6-amino-2-naphthoic acid; β-CD, β-cyclodextrin; BDF, bis-dimethylaminofuchsone; BM, Brooker’s merocyanine; C343, Coumarin 343; DANDSA, 5, 6-diamino-naphthalene-1,3-disulfonic acid; MV, methylene violet (Bernthsen); PB, phenol blue; 4PP, 4-pyridinium phenolate.
The slow appearance of spectra (     ) and the correlation between detector polarity and degree of response suggests some kind of synergistic process or resonant interaction taking place between detector and potency in which the polarity of both are gradually strengthened. The success and magnitude of such an interaction may well depend upon several factors (see below).
Several other insights emerge from . It is clear that in contrast to the ground or permanent dipole moment, the transition dipole moment (the difference between ground and excited states) is not an indicator of response to potencies and there does not appear to be any correlation. For instance, amino acids with an aromatic bridge such as ANA and DANDSA have negligible transition dipole moments, yet demonstrate responses. Pyridinium phenolates all have very large transition dipole moments of c. 20–22D  yet display modest spectral changes ().
Dipole moment size may not be the only determinant underlying response to potencies, however. MV is a conformationally rigid molecule compared with, for example, 4PP, which has a similar dipole moment, and yet there exists a significant difference in the magnitude of their responses to potency. Furthermore, BM is conformationally mobile and produces modest and very variable responses, and yet on encapsulation, which renders it more rigid, response increases considerably. These results may indicate that molecular rigidity is required for potencies to effectively engage with molecular detectors. Additional evidence for this proposition comes from results with C343 where response to potencies is greater than for 4PP and ET33 ().
Using a range of compounds, both solvatochromic and non-solvatochromic, has not only demonstrated that specific molecular features (large dipole moment, electron delocalisation, polarizability and molecular rigidity) appear to be important for interactions with potencies to take place, but it has also revealed that several steps are involved in the production of spectral changes indicative of these interactions.
Results pooled from all 10 compounds reported in this study indicate that there are three steps in the interaction between potencies and molecular detectors that produce the spectral changes seen. While not all steps are separately observable in all compounds so far tested, it seems likely that these steps are a common feature given the number of overlaps between results.  summarises results for all compounds investigated and reported herein.
Abbreviations: ABA, 4-aminobenzoic acid; ABPA, 4′-amino-[1,1′-biphenyl]-4-carboxylic acid; ANA, 6-amino-2-naphthoic acid; β -CD, β -cyclodextrin; BDF, bis-dimethylaminofuchsone; BM, Brooker’s merocyanine; ET33, 2, 6-dichloro-4-(2, 4, 6-triphenyl-pyridinium-1-yl)-phenolate; DANDSA, 5, 6-diamino-naphthalene-1,3-disulfonic acid; MV, methylene violet (Bernthsen); 4PP, 4-pyridinium phenolate.
a Not investigated.
b BDF pKa1 represents BDF + H+↔ BDF-H+ and pKa2 BDF + OH–↔ BDF-OH–.
c Relative aggregation levels observable by resonant light scattering (this study).
d Relative aggregation levels observable by fluorescence spectroscopy (this study).
e Relative aggregation levels observable by UV-vis and fluorescence spectroscopy (this study, see text for more details).
Step one appears to involve a primary interaction between potency and molecular detector, resulting in an electron density shift. This step is observable with positively and negatively solvatochromic dyes. Both are made more polar—the former having their excited (charged) state stabilised, and the latter having their ground (charged) state stabilised.
Step two follows on from step one and is a consequence of it. Any electron density shift in a delocalised system will cause a change in one or more of any ionisable groups attached to that system. For all compounds assayed, changes in pKa values are seen. For amino acids with an aromatic bridge, this is the first observable step as these compounds do not have the spectral characteristics of solvatochromic dyes and hence step one is silent. While not solvatochromic, aromatic bridged amino acids, which are zwitterionic, produce significant interactions with potencies. These results taken together suggest that potencies preferentially interact with polar species, rendering them more polar. Indeed, the more polar the detector, the more effect potency seems to have ().
Step three results from step two. Any change in pKa values and hence degree of protonation will affect aggregation levels, as the forces driving aggregation include ionic as well as hydrophobic interactions and hydrogen bonding. Step three is most clearly separately observable with DANDSA, but is also apparent with compounds such as BDF and MV.
A final observation may have some relevance to the discussion that follows. A previous study has found that sustained light exposure inhibits the BDF–potency interaction, and continuous irradiation results in no observable spectroscopic difference between dye–control and dye–potency solutions. This observation has now been extended to include 4PP, ET33, BM, MV and ANA. In all cases, no effect of potency is seen with any of the above compounds on continuous irradiation (usually at the absorbance maximum of the dye). Short exposure to light (i.e., during assay in the spectrophotometer) has little effect, so continuous exposure is necessary to fully inhibit the dye–potency interaction. In addition, any loss of spectroscopic differences from medium term light exposure to dye–potency solutions can be reversed by placing solutions in the dark.
Consequently, to avoid complications created by light exposure, and as described in the Materials and Methods, all dye–potency and dye–control incubations are performed in the dark and assays performed at intervals, with incubations being returned to black film canisters in between assays.
Curiously, however, irradiation of potency solutions themselves appears to have no deleterious effect, at least over the short term. In addition, all aromatic bridged amino acid–potency solutions are scanned down to at least 230 nm, and often 220 nm, when assayed. This is well into the UV region of the electromagnetic spectrum, and yet no obvious loss of potency strength has been observed. It may be that potencies are far more robust than previously thought and that any UV-induced inactivation is slow and requires multiple exposures.
Why potency solutions themselves appear to be immune to light exposure and yet dye–potency interactions are sensitive remains unclear at this stage. It is likely, however, to be saying something fundamental about the physico-chemical nature of potencies.
Returning to dipole moment size and degree of response in relation to the putative step one above, it would seem that the larger the dipole moment of molecular detectors, the larger the response to potencies. This implies that potencies require polarity to interact, and on interaction increase the polarity of detectors proportionately. This in turn suggests potencies themselves must have polarity to result in this kind of interaction, as has been put forward previously. Any proposal as to the possible physico-chemical nature of potencies must, therefore, include polarity in the proposal.
Several well-known facts about potencies are perhaps worth reconsidering at this point.
The first is that potency solutions are prepared and stored as water–alcohol mixtures, often with the proportion of alcohol present as high as 90%.
Second, homeopathic potencies are dispensed most usually in the form of tablets. Both of these facts argue against water as being the source of potencies, but allow for the possibility that water, alcohol, and lactose may be carriers.
Third, potencies can be administered by olfaction. Indeed, Hahnemann and many of his colleagues and followers used this method.
Finally, both trituration and succussion have a feature in common, and that is friction. Both grinding and vigorous shaking are forms of friction, or the action of one surface against another.
Combining the above observations–namely, that potencies have polarity, potencies are created by friction, potencies may be administered by olfaction, and water, alcohol, or lactose are unlikely to be the source of potencies (but may be carriers)–it is difficult to avoid the possibility that potencies might be some form of non-thermal plasma, however improbable that may seem. Non-thermal plasmas are produced by friction. Indeed, both triboplasma (plasma produced by grinding) and cavitation plasma (through violent shaking of solutions and bubble implosion) are well-documented phenomena. Plasmas are composed of free ions and as such become highly polarised under the influence of electrical and magnetic fields. If such plasmas were stable, they could be administered by olfaction. That plasmas emit light may also be relevant to the observation that some curious relationship exists between potency action and the necessity to keep light excluded from dye–potency solutions.
The improbability of the suggestion that potencies may be non-thermal plasmas carried by polar vehicles, such as water, alcohol and lactose, lies however in the transitory nature of, and the high levels of energy required to sustain plasmas for any length of time. Nevertheless, there have been several proposals over the years, including recently, that potencies and plasmas share much in common and that succussion does, momentarily, produce plasma. Clearly more would need to be done to strengthen or discount the possibility that potencies may be some form of non-thermal plasma.
The present study has demonstrated that a wide range of compounds under the general category of π-conjugated dipoles respond to homeopathic potencies. These include solvatochromic dyes as well as amino acids with an aromatic bridge (π-conjugated zwitterions), which carry formal charges at either end of their delocalised systems. This greatly extends the number of molecular detectors available and has provided valuable insights into the fundamental nature of potencies. Solvatochromic dyes now appear to be a sub-set of a much wider group of compounds sensitive to serially succussed and diluted solutions. The necessary requirements for sensitivity to potencies appear to be electron delocalised systems that have a large permanent or ground dipole moment, together with the ability of the system to be polarised, meaning their electron density is free to move spatially across the molecule under the influence of appropriate stimuli. The larger the permanent or ground dipole moment of such compounds, the more they are polarised in the presence of potencies. In addition, molecular rigidity appears to be an important structural component of molecular detectors and improves responsiveness further.
Amino acids with an aromatic bridge demonstrate significant responses to potencies, and results with these compounds, particularly DANDSA, have confirmed and extended those reported previously with solvatochromic dyes. The large dipole moments and molecular rigidity of these π-conjugated zwitterions appear to be responsible for their responses to potencies.
Using a combination of extensive screening of potential molecular detectors of different structures, molecular encapsulation with β-CD and assaying at pH values both near pKas of compounds, as well as at pH values far removed from their pKa values, has revealed that the generation of difference spectra proceeds in three steps. The first step appears to involve the primary interaction of potency and molecular detector, producing a shift in electron density across the molecule. This step can be detected using solvatochromic dyes, which are encapsulated with β-CD and assayed ± potency at pH values well away from the pKa value of the dye. Positively solvatochromic dyes exhibit a bathochromic shift in their spectra, indicating stabilisation of the dyes’ excited (and more polar) state, while negatively solvatochromic dyes exhibit a hypsochromic shift in their spectra, indicating stabilisation of the dyes’ ground (and more polar) state.
The second step can be detected in all compounds assayed at pH values ≈ pKa values and is the result of the first step. Electron density shift in step one results in a change in pKa values and protonation levels, which produce spectroscopic changes characteristic of each compound.
The third step can be most clearly seen with the molecular detector DANDSA owing to the very different spectra of aggregated and disaggregated material, and where a change in protonation levels leads much more slowly to enhanced aggregation of the compound in the presence of potency. The third step can also be discerned with MV and BDF, using a combination of UV-vis and fluorescence spectroscopy ().
Finally, it has been proposed that the possibility that potencies are some form of non-thermal plasma should at least be entertained, despite the obvious objections that such a proposal raises. The apparent polarity of potencies, their generation through friction, their storage in ethanol/water mixtures and on lactose, together with the observation that they can have their clinical effect through olfaction, argues against any kind of standard pharmaceutical formulation and points more towards an electromagnetic identity for potencies. The observation that dye–potency interactions are inhibited by light only further emphasises this possibility.
Non-thermal plasma: A partially ionised gas at room temperature in which electrons are free and not bound to any atom or molecule. Plasmas exhibit many interesting properties including sensitivity to, and the generation of, electromagnetic fields, collective behaviours, dissipative structures, coherence and self-organisation. Plasmas also have electron oscillation frequencies.
π-conjugated dipole: A molecule in which there is a higher electron density at one end than the other and where both ends are connected by an electron bridge of delocalised or free electrons. A π-conjugated zwitterion is where the electron density disparity between each end of the molecule is such as to have become formal positive and negative charges. Electron density is free to move along the length of π-conjugated dipoles under the influence of appropriate stimuli, such as electromagnetic fields.
Solvatochromism: The ability of a chromophoric compound to change colour with a change in solvent polarity. This is due to a difference in the dipole moment between the ground and excited states of the chromophore and involves a spatial movement of electron density along the length of the molecule under the action of an appropriate stimulus such as light. Solvatochromic compounds are π-conjugated dipoles and as such are also sensitive to the presence of electromagnetic fields.
Conflict of Interest
No source of funding had any influence on the design, analysis, interpretation or outcome of the research contained within this manuscript, nor on the writing of the manuscript.
Funding for this work is gratefully acknowledged from The Homeopathy Research Institute, UK; Standard Homeopathic Company/Hylands, USA and The Tanner Trust, UK.
- 1 Cartwright SJ. . Homeopathy 2016; 105: 55-65
- 2 Cartwright SJ. . Homeopathy 2017; 106: 37-46
- 3 Reichardt C, Welton T. . Weinheim: Wiley-VCH; 2011: 365-367
- 4 Thayer MP, McGuire C, Stennett EM. , et al. . Spectrochim Acta A Mol Biomol Spectrosc 2011; 84: 227-232
- 5 Halpern A, Ramachadran BR. . Photochemistry and Photobiology 1995; 62: 686-691
- 6 Gainer A, Stevens JS, Suljoti E. , et al. . 16th International Conference on X-ray absorption fine structure (XAFS16); Journal of physics conference series 2016; 712: 1-4
- 7 Jara GE, Solis CA, Gspooner NS. , et al. . Dyes and Pigments 2015; 112: 341-351
- 8 Ronzani F, Trivella A, Bordat P. , et al. . J Photochem Photobiol Chem 2014; 284: 8-17
- 9 Davis F, Higson S. . In . New York, NY: Wiley; 2011: 190-244
- 10 Holt JS, Campitella A, Rich A, Young JL. . J Incl Phenom Macrocycl Chem 2008; 61: 251-258
- 11 Steiner U, Abdel-Kader MH, Fischer P, Kramer HEA. . J Am Chem Soc 1978; 10: 3190-3197
- 12 Gonzalez D, Neilands O, Rezende MC. . J Chem Soc, Perkin Trans 2 1999; 4: 713-717
- 13 Albert A, Sergeant EP. . In . London: Chapman and Hall; 1971: 76-81
- 14 Perrin DD, Dempsey B, Serjeant EP. . London: Chapman and Hall; 1981
- 15 Davis F, Higson S. . New York, NY: Wiley; 2011: 325-368
- 16 Minkin VI, Osipov OA, Zhdanov YA. . New York, NY: Springer; 1970
- 17 Niewodniczański W, Bartkowiak W. . J Mol Model 2007; 13: 793-800
- 18 Wyn-Jones J, Gormally J. . Amsterdam: Elsevier; 1983
- 19 Hahnemann S. . 5th and 6th eds
- 20 Meichsner J, Schmidt M, Schneider R, Wagner HE. . Boca Raton: CRC Press; 2013
- 21 Nakayama K. . In: Wang QJ, Chung YW. , eds. Encyclopedia of Tribology. New York, NY: Springer; 2013: 3750-3760
- 22 Nikitenk SI. . Adv Phys Chem 2014; 2014: 173878
- 23 Hibou F. . Homeopathy 2017; 106: 181-190
Address for correspondence
Steven J. Cartwright, PhD
DiagnOx Laboratory, Cherwell Innovation Centre
Upper Heyford, Oxon, OX25 5HD